",isbn:"978-1-80356-966-6",printIsbn:"978-1-80356-965-9",pdfIsbn:"978-1-80356-967-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"f86a9f720cc3ac0f1c385d0367ea89b9",bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11624.jpg",keywords:"Agricultural Waste, Reuse, Reduction, Soil Health, Recycling, Agriculture and Environment, Modelling and Simulation, Agro-Industrial Waste, Bioresource Processing, Processing and Management, Crop Residue, Forest Waste",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"17 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Fiaz Ahmad is a researcher in the field of Agricultural Engineering with fifteen years of field and academic experience, currently in charge of the Agricultural Machinery Design Laboratory at Bahauddin Zakariya University. He applied for two patents at the national level.",coeditorOneBiosketch:"A renowned researcher in the field of Agricultural Engineering with 14 years of academic experience at Bahauddin Zakariya University. Winner of various prestigious fellowships, awards, and research grants. Published 250+ articles along with several books and chapters. Guest editor of seven ISI-SCI journals for publishers like SAGE, MDPI, and Frontiers.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",middleName:null,surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/338219/images/system/338219.png",biography:"Dr. Fiaz Ahmad is an assistant professor and lecturer at the Department of Agricultural Engineering, Bahauddin Zakariya University, Multan, Pakistan. He obtained his Ph.D. in Agricultural Bioenvironmental and Energy Engineering from Nanjing Agriculture University, China, in 2015, and completed his postdoctorate in Agricultural Engineering from Jiangsu University, Zhenjiang, China, in 2020. He was awarded a fellowship from the Higher Education Commission of Pakistan for Ph.D. studies and from the Chinese Government for post-doctoral studies. He earned a BSc and MSc (Hons) in Agricultural Engineering from the University of Agriculture, Faisalabad, Pakistan, in 2004 and 2007, respectively. He is the author of more than fifty journal and conference articles. He has supervised six master’s students to date, and is currently supervising six master and two doctoral students. Dr. Ahmad has completed three research projects with his research interest focusing on the design of agricultural machinery, agricultural waste management, artificial intelligence (AI), and agricultural bioenvironment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:{id:"199381",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sultan",slug:"muhammad-sultan",fullName:"Muhammad Sultan",profilePictureURL:"https://mts.intechopen.com/storage/users/199381/images/system/199381.png",biography:"Muhammad Sultan is an Assistant Professor at the Department of Agricultural\r\nEngineering, Bahauddin Zakariya University, Multan (Pakistan). He completed his Ph.D.\r\nand Postdoc from Kyushu University (Japan) in the field of Energy & Environmental\r\nEngineering. He was an awardee of MEXT and JASSO fellowships (from the Japanese\r\nGovernment) during Ph.D. and Postdoc studies, respectively. He also did a Postdoc as\r\na Canadian Queen Elizabeth Advance Scholar at Simon Fraser University (Canada) in\r\nthe field of Mechatronic Systems Engineering. He worked for Kyushu University\r\nInternational Institute for Carbon-Neutral Energy Research (WPI-I2CNER) for two years.\r\nCurrently, he is working on 4 research projects funded by the Higher Education\r\nCommission (HEC) of Pakistan. He has completed six projects in past in the field of\r\nagricultural engineering. He has supervised 10+ M.Eng. and Ph.D. thesis and 10+\r\nstudents are currently working under his supervision. He has published 120+ journal\r\narticles, 100+ conference articles, 13 book chapters, and 6 books. He is serving as guest\r\neditor for the journals like Sustainability (MDPI), Agriculture (MDPI), Energies (MDPI),\r\nAdvances in Mechanical Engineering (SAGE), Frontiers in Mechanical Engineering, and\r\nEvergreen Journal of Kyushu University. His research is focused on developing energy-\r\nefficient temperature and humidity control systems for agricultural storage, greenhouse,\r\nlivestock, and poultry applications. His research keywords include desiccant air-\r\nconditioning, evaporative cooling, adsorption heat pump, Maisotsenko cycle (M-cycle),\r\nenergy recovery ventilators; adsorption desalination; wastewater treatment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440212",firstName:"Elena",lastName:"Vracaric",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440212/images/20007_n.jpg",email:"elena@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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\n\t\t\t
1. Introduction
MODICAS (modular interactive Computer Assisted Surgery) represents an integral solution for the software-based combination of a surgical planning software, an optical localization device and a haptic sensor with a mechatronic manipulator in order to support surgical interventions. One key feature of the integral system is to accurately and precisely align any surgical instrument, according to the preoperative planning, in relation to the bony structure of the patient and to intraoperatively ensure the alignment to remain constant all the time. This is made possible due to the automatically controlled tracking of small patient movements in real time. As a result of developed calibration algorithms, the stationary precision and accuracy of the whole system is mainly defined by the measurement characteristics of the applied localization device. Moreover, the actual exploratory focus lies on the enhancement of the dynamic behaviour, especially on the reduction of the dynamic tracking error without concurrently degrading the stationary properties. The following chapter describes the development and use of an offline simulation environment for the analysis and the enhancement of the MODICAS patient tracking system dynamics. At first, the functional principle of the tracking procedure is discussed. Furthermore, the physical modelling of all relevant system characteristics and the identification of the system parameters are described. Additionally, the model behaviour is verified against measurements from the real surgical assistance system. It is shown, that the offline model properly simulates the behaviour of the real system. As an example of use, a comparison of three tracking control strategies is shown on the basis of the developed and identified model. In the future, further simulations will be performed, in order to understand how various system parameters like lags, measurement noise or calibration errors may influence the overall tracking performance. The results will lead to a conclusion about the actual technical constraints and to an outlook on how such system can be further advanced in the future.
\n\t\t
\n\t\t\t
2. The modiCAS surgical assistance robot
\n\t\t\t
The concept of the MODICAS surgical assistance system, as shown in Fig. 1 during a clinical trial, has been already introduced in Castillo Cruces et al. (2008). The major goal of its concept is to combine a robot manipulator {rbs} with a common surgical navigation or localization system {ots} respectively to one integral unit (Fig. 2). To be precise, we use a PA10 Series General Purpose Robot from MITSUBISHI HEAVY INDUSTRIES (MHI) as manipulator and a NDI POLARIS P4 Optical Tracking System {ots} as localizer. This integrated device helps the surgeon to accurately and precisely align any surgical instrument {ttp} relatively to the patient’s anatomy {arb}, exactly as defined in the computer assisted preoperative planning.
\n\t\t\t
Figure 1.
Clinical trial utilizing the MODICAS assistance robot for total hip arthroplasty implantation
\n\t\t\t
Figure 2.
Coordinate systems – {ots} localizer (optical tracking system), {arb} patient (aim reference body), {rrb} (robot reference body) {rbs} robot base, {tcp} robot wrist (tool center point), {ttp} tool tip
\n\t\t\t
Utilizing a robot manipulator for such positioning tasks offers significant advantages in contrast to pure navigation systems. First, a robot manipulator guided by a precise localization system can position any surgical instrument with a very high precision for a long period of time, without tremor, exhaustion or the possibility of slipping. Second, the surgeon, who is released from the monotonous but straining positioning task, can fully concentrate on the main focus of the intervention, for instance what force he applies to the bony structure when he mills or drills using any wrist-mounted, manually controlled instrument.
\n\t\t\t
One key feature of the MODICAS assistance system is that it does not behave fully autonomously but highly interactively in order to cooperatively assist the surgeon. Therefore, much development work has been concentrated on the cooperative haptic interaction interface, as described in Castillo Cruces et al. (2008).
\n\t\t\t
One further research and development goal is to make a rigid fixation of the patient unnecessary by integrating an online tracking function that automatically updates the pose of the aligned instrument in real time if the patient moves. Reducing the dynamic error without degrading the stationary precision of such tracking functionality is a challenging task. In practice, the reachable dynamics and precision are bounded by technical constraints of the system components. Thus, the robot control must be carefully adopted to those system parameters. A reliable simulation model of the whole tracking procedure will be helpful to get a better understanding of the patient tracking principle and the influence of various system parameters on the tracking quality. The development of such a model and the identification of its dynamic parameters, as well as one example of use, will be the focus of this article.
\n\t\t
\n\t\t
\n\t\t\t
3. Real time tracking of patient’s movements by the robot
\n\t\t\t
Due to the fact that the MODICAS patient tracking procedure is carried out by the use of an optical tracking system, it can be characterized as a so called ’visual servoing system’, like already described in Weiss et al. (1987). In the past, visual servoing approaches have been categorized in detail, depending on the type of e.g. camera or control principle. A generalized overview is given in Kragic & Christensen (2002). This section will illustrate how the MODICAS patient tracking procedure works, by categorizing it and establishing its kind of implementation.
\n\t\t\t
The PA10 robot arm from MHI is shipped as a modular system that allows three different ways of interfacing. The easiest way is to use a dedicated MOTION CONTROL BOARD (MHI MCB) that carries out the entire basic functionality which is typically provided with common industrial robots e.g. like forward and inverse kinematics calculations, control in cartesian or joint space and trajectory path planning. The MHI MCB was utilized within the first generation of the MODICAS assistance system in order to fulfill the general proof of principle of the overall MODICAS concept. The experiences with that first prototype emphasized the necessity of interfacing the robot on a lower level in order to implement new desired features. For instance, such features are a singularity robust haptic interface, virtual motion constraints, calibrated kinematics or in general the possibility to influence the dynamic behaviour of the controlled robot in a more direct way. For such purpose, the robot can be interfaced through direct joint control. Either in torque mode, where control commands are directly interpreted by the robot as joint torque commands and straightly turned into motor currents. Or in velocity mode, where the control commands are interpreted as velocity commands and the tracking of the velocity command trajectories is carried out jointwise by internal PI Controllers per each servo. Even though promising approaches are existing in literature concerning model-based computed torque control of a PA10 robot (Kennedy & Desai (2004), Bompos et al. (2007)), one global development strategy for the actual MODICAS prototype was fixed to retain a cascade control structure for joint angle control, where the servodriver-internal PI velocity controllers robustly compensate disturbances or physical effects like e.g. gravity, coriolis force and friction, respectively.
\n\t\t\t
If the robot kinematics, describing the geometric relation between the joint angles and the robot wrist pose, are exactly calibrated and further the geometric relation between the base coordinate frames of camera {ots} and robot {rbs} is also exactly known and rigidly fixed, then it would be possible to omit the optical tracking of the robot wrist {rrb}. Only the optical tracking of the patient’s pose {arb} would be necessary in order to generate a corresponding joint angle command vector \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t→\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t=\n\t\t\t\t\t\t\t\tf\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t(\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\ta\n\t\t\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\t\to\n\t\t\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\t\t\ts\n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t)\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\n\t\t\t
\n\t\t\t
for the robot controller in order to track patient’s movements. Such assembly is defined in Kragic & Christensen (2002) as ’endpoint open loop’ configuration.
\n\t\t\t
Certainly, common uncalibrated robot manipulators have significant kinematic errors. Due to manufacturing tolerances, the real kinematics differ from their nominal model. This leads to a reduced positioning precision depending on the dimension of kinematic errors, even if the manipulator has a good repeatability (Bruyninckx & Shutter (2001)). Further it is extremely challenging to permanently guarantee an exactly fixed geometric relationship between the base coordinate systems of the robot and the camera, if the camera acts from an observer perspective (outside-in or stand-alone, as defined in Kragic & Christensen (2002), respectively). Therefore, within the MODICAS tracking procedure, the robot wrist is optically tracked as well. That facilitates the compensation of kinematic errors or changes in the geometric relationship between the camera’s and the robot’s base frame. Due to the additional optical tracking of the robot wrist or end effector respectively, such assembly is defined as ’end point closed loop’ configuration.
\n\t\t\t
In principle, due to the optically closed loop, an underlying feedback from the robot’s joint encoders is not essentially required to perform visual servoing. Omitting such joint encoder feedback would lead to a so called ’direct visual servoing’ system, where the dynamic control of the robot is carried out directly through the optical feedback loop.
\n\t\t\t
Due to the fact that typical surgical optical tracking systems like the NDI-POLARIS have a relatively low bandwidth in contrast to common robot joint encoders, it is reasonable to use a so called look and move approach. Here, the potential of precise but maybe slow optical sensors to compensate kinematic errors is profitably combined with the higher bandwidth of the joint encoders by retaining the joint encoder feedback.
\n\t\t\t
By the reason that surgical optical tracking systems commonly deliver full position and orientation of all tracked elements in the three-dimensional space, the robot control can be performed ’position based’. The opposite of position based is ’image based’, where the control law is directly based on raw image features instead of fully determined 3D pose data.
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Finally, due to the utilization of a stereo vision system which is not rigidly fixed to the robot wrist (like inside-out or eye in hand systems, as defined in Kragic & Christensen (2002), respectively), but acts from an observer perspective (Fig. 2), we can classify the MODICAS patient tracking approach as position based dynamic look and move using outside-in stereovision in endpoint closed loop configuration.
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A block diagram of the MODICAS patient tracking principle is illustrated in Fig. 3. Here, the robot is dynamically controlled in joint space. Due to that it is interfaced in velocity mode, all joints are velocity-controlled by their servodriver-internal PI controllers that cannot be modified. However, the overlying joint angle control loops may be customized in order to adapt the dynamic behaviour at the best to the desired patient tracking functionality. Available input signals for implementing any desired joint angle controllers are the joint angle command vector\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t\t\t→\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tc\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t, the joint angle feedback vector \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t→\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t and the joint velocity feedback vector\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t→\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t.
\n\t\t\t
In order to follow patient’s movements, the control input for the decentralized joint control of the robot must represent the joint angle vector
where the inverse kinematics IK give the joint angle vector \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t\t\t→\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tc\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\tthat corresponds to that robot arm configuration \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\tc\n\t\t\t\t\t\t\t\t\t\tp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\ts\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\twhere the robot wrist strikes a desired pose \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\tc\n\t\t\t\t\t\t\t\t\t\tp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\ta\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\trelatively to the patient’s reference pose.\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\ta\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\ts\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\n\t\t\t
\n\t\t\t
If the determination of the patient’s pose is carried out through an outside-in localization system in endpoint closed loop configuration, then the tracking algorithm results in a direct geometric coordinate transformation equation such that
where FK are the forward kinematics calculated on the basis of the actual robot joint angle measurements \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t→\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t;\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\tc\n\t\t\t\t\t\t\t\t\t\tp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\tis a constant matrix derived from the robot to localizer calibration; \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\tc\n\t\t\t\t\t\t\t\t\t\tp\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\ta\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\tis the desired constant pose or trajectory of the robot wrist relatively to the patient reference frame; \n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\to\n\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\ts\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t,\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\ta\n\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\tb\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\to\n\t\t\t\t\t\t\t\t\t\tt\n\t\t\t\t\t\t\t\t\t\ts\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\tare the frames of the optically measured reference bodies and E is the optically determined pose error matrix.
\n\t\t\t
Primally when the optically measured pose of the robot wrist is exactly the same as the desired one relatively to the optically measured pose of the patient, then the equation
where I is the identity matrix, is fulfilled, such that the system is compensated and the actually measured joint angles are directly fed through as setpoint values
However, if any pose error E occurs due to displacement of the patient {arb}, the localizer {ots} or the robot base {rbs} or due to kinematic uncertainties, the tracking algorithm geometrically calculates the desired robot wrist pose that is needed to fulfill equation 3. The dynamic compensation rather takes place in joint space and is carried out through the joint angle controllers. Thus, a manipulation of the tracking dynamics is exclusively carried out by adapting these joint angle controllers.
\n\t\t\t
The functional separation of the tracking procedure into a geometrically setpoint determination and into a dynamic control exclusively in joint space facilitates the use of classical approaches from control theory for each joint in order to design a fast and robust tracking controller.
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\n\t\t
\n\t\t\t
4. Simulation model describing the real time tracking procedure
\n\t\t\t
Regarding the objective of tuning the MODICAS tracking procedure at the best, a reliable model-based environment, that exactly represents the real world, facilitates watching process variables or changing parameters that are not observable or manipulable respectively within the real system, yet. For instance, such model-based environment allows experiments e.g. regarding the questions, how far the tracking procedure may be improved with upcoming faster localization systems that are not available yet, or how far miscalibration or kinematic errors affect the system stability without the presence of any accidental risk. The following sections illustrate the dynamic model that has been developed with the objectives to perform a detailled offline analysis of the MODICAS patient tracking procedure and to find the best system tuning in view of all current and persisting technical constraints.
\n\t\t\t
Figure 3.
Block diagram of the MODICAS real time patient tracking procedure
\n\t\t\t
\n\t\t\t\t
4.1. Global model structure
\n\t\t\t\t
The global structure of the offline model is directly derived from the block diagram in Fig. 3 which describes the tracking procedure. The forward and inverse kinematics as well as the tracking algorithm itself are straightly copied from the real control software that previously has been implemented within the MODICAS real time control development environment. This environment has been introduced in Schneider & Wahrburg (2008).
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\n\t\t\t\t
4.2. Robot model
\n\t\t\t\t
The model of the robot arm itself consists of a stiff kinematic model and six structurally identical dynamic joint models with individual joint specific parameters.
\n\t\t\t\t
The kinematic model, as well as the nominal model in the robot controller, are based on the so called 321-kinematic structure which is further described in Bruyninckx & Shutter (2001). Due to some simplifying conventions concerning the kinematic structure, the 321-kinematics model saves some geometric parameters and thus significant computational load in contrast to a common Denavit-Hartenberg model. As a result of that simplification, a full identification and thus an exact simulation of the real kinematic errors will not be possible as long as the 321- kinematics model is used. For that purpose, a full implementation of the Denavit-Hartenberg convention would be necessary. However, for simple experiments on how kinematic uncertainties affect the behaviour of the tracking procedure, it is sufficient to merely simulate joint angle offsets as well as link length errors (Fig. 4).
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Figure 4.
Robot model - kinematics and joint servo dynamics
\n\t\t\t\t
Regarding the dynamics, any disturbances or physical effects like e.g. gravity, that act on the gear sides of the real robot joints, are strongly reduced at the motor sides through high gear ratios and therefore relatively small in relation to the inertias of the joint servo rotors. Further, due to the fact that, within the MODICAS system, the PA10 robot is interfaced in velocity mode, such effects are quickly compensated through the servodriver-internal PI velocity controllers. Therefore, it is adequate to model every joint drive as a simple PI-controlled dc-motor as it is illustrated in Fig. 4, in order to authentically simulate the dominant dynamic behaviour of the robot arm in velocity mode. All joint model parameters are listed in Tab. 1.
\n\t\t\t\t
Those parameters that cannot be determined straightly from available technical data sheets of the robot, are identified by fitting the velocity step response of every joint model into its corresponding measurement from the real system. The estimation of the unknown parameters is carried out through fmincon() from the MATLAB OPTIMIZATION TOOLBOX
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Table 1.
parameters of one joint model
\n\t\t\t\t
which manipulates all unknown parameters within user defined constraints and performs a simulation per each parameter set, until a quality function, defined as
reaches a minimum, where qms is the measured and qsm the simulated joint angle, \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t\t·\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\tms is the measured and \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\tq\n\t\t\t\t\t\t\t\t\t\t·\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\tsm the simulated angular velocity and a1, a2 are manipulable weighting gains.
\n\t\t\t\t
\n\t\t\t\t\tFig. 5 shows the result of the described identification procedure, exemplarily for the first shoulder joint of the robot (S1). Due to the simple structure of the joint model, the torque curve is strongly idealized. However, the model reproduces the angle and angular velocity trajectories of the real joint drive very well, if stimulated with the same velocity command like the real one. In order to check if these characteristics are reproducible over the full workspace of the robot, independently from payload, robot arm configuration or input signals, several verification tests were done. Exemplarily, Fig. 6 shows a verification result where, due to a changed robot arm configuration (see Fig. 7), a lower moment of inertia acts on the joint S1 and further the velocity command is 0.1 \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\t\tr\n\t\t\t\t\t\t\t\t\t\t\ta\n\t\t\t\t\t\t\t\t\t\t\td\n\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\t\ts\n\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\thigher than during the identification process. The simulation is carried out using exactly the same parameters as in the experiment illustrated in Fig. 5. Even though the real torque characteristics differ between the two experiments due to a changed moment of inertia acting on joint S1, the simulated angle and angular velocity trajectories always exactly represent the corresponding measurements from the real joint drive. Thus, the developed dynamic joint models are fully adequate to simulate the dynamic behaviour of the robot within the tracking procedure.
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4.3. Localizer model
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At the actual state of development, the localizer model merely simulates the time performance of the NDI-POLARIS-System and normally distributed spatial measurement noise, whereas the sampling time ΔTots as well as the measurement lag tlots can be globally changed and the standard deviation for each component of a measured pose (x,y,z,,,) can
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Figure 5.
Simulation results using the identified servo model compared to real measurements (dataset for identification), exemplary for the first shoulder joint (S1)
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Figure 6.
Simulation results using the identified servo model compared to real measurements for the first shoulder joint (S1) in one exemplary scenario different to the identification scenario
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Figure 7.
Differing poses for robot dynamics identification (left) and exemplary verification (right)
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be individually manipulated for each simulated reference body. Further, miscalibration between the robot wrist {tcp} and its optical reference body {rrb} can be simulated through multiplying a corresponding error transformation matrix T.
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The localizer model is actually kept that simple because the current focus lies in exploring how the time performance of any (replaceable) localizer influences the overall tracking behaviour. If a strongly detailed measurement error model of the NDI-POLARIS with its anisotropic measurement characteristics will be desired, mathematical models like e.g. from Wiles et al. (2008), an extension of Fitzpatrick et al. (1998), can be integrated into the dynamic model of the MODICAS patient tracking procedure in the future.
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4.4. Model verification
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The full dynamic model that is described above, consisting of the robot model, localizer model, kinematics and tracking algorithms, is verified against measurements from the real MODICAS assistance system while tracking random patient movements. In order to better enable the recognition of dynamic transients in the laboratory, the applied patient motion is much faster than typically expected during any surgical intervention. The results of one verification experiment are presented in Fig. 8 as cartesian trajectories. The corresponding time trajectories of the robot joint angles are further illustrated in Fig. 9. As it can be seen in Fig. 9, especially in the plots for the joints E1 and W1, there are noticeable differences between the simulated and the measured time trajectories of the joint angles. What firstly seems to be a weak point of modelling, is a valuable feature of the tracking principle from equation (3). Not only does the observed level deviation occur in the joint responses, but it also occurs in the joint angle command trajectories. The reason for that phenomena is that, for the exemplarily presented simulation, no kinematic error has been considered in the model. While the real uncalibrated robot has significant kinematic errors, in the simulation all parameters for link length errors and joint offsets (Fig. 4) were set to zero. Although the real robot has significant kinematic errors, the tracking algorithm within the real system
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Figure 8.
Verification of the overall tracking procedure model by comparing the model output signals to real measurements (cartesian time trajectories of robot wrist pose)
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adjusts the joint angle trajectory commands such that the cartesian trajectories match those of a kinematically precise robot (as simulated in Fig. 8). Accordingly, there will not remain any kinematically caused deviation between the actual and desired pose of the robot wrist in steady state. All in all, Fig. 8 clearly indicates that the simulation of the MODICAS patient tracking function represents the real system behaviour very well and the developed simple model is fully adequate for further investigations, in presence of a joint velocity interfaced robot.
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Figure 9.
Verification of the overall tracking procedure model by comparing the model output signals to real measurements (time trajectories of robot joint angles)
One of the first simulation experiments that have been performed using the novel offline model environment was aimed to compare different control strategies, especially adopted to the time performance of the NDI-POLARIS, at first under the consumption of zero measurement noise. A more general investigation on different control structures within (image based) visual closed loop systems has been already presented in Corke & Good (1996). However, our investigation is specially aimed at finding the best possible control strategy
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Figure 10.
Comparison of three different control strategies - 1. original proportional controller, 2. proportional with feedforward, 3. pole placement controller
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for the MODICAS patient tracking procedure with its functional principle like shown in Fig. 3. As communicated through the manufacturer, only a proportional controller per each joint is generally implemented into the original MHI MCB. With the help of the model-based simulation environment we found out that, regarding the patient tracking function, a specially tuned proportional feedforward controller enhances the overall tracking behaviour, although the feedforward velocity signal, that can be derived from the NDI-POLARIS through a simple differentiation, is poor due to the relatively low sample rate in relation to the time response of the robot.
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A further enhancement has been carried out by the use of a pole placement controller, especially developed and adopted to the time performance of the NDI-POLARIS. The results of the two enhanced controllers may be compared to the original one from the MHI MCB by reckoning Fig. 10. In the experiment, a patient dummy is rotated around a defined axis that is assumed to be the principal axis of the patient. The measurement of the patient dummy’s reference body is fed into the offline model, where the patient tracking procedure is simulated three times using three different controllers. First, the proportional controller with the original controller gains from the MHI MCB, second the specially tuned proportional feedforward controller and third, the specially developed pole placement controller. As the plots show, in the exemplary tracking experiment, the maximum 3D positioning error is reduced when using the proportional feedforward controller and further reduced when using the pole placement controller. Upcoming experiments will further show how far those controllers can be sufficiently be utilized in the presence of measurement noise or how to then find the best compromise between fast dynamics and high accuracy as well as precision in steady state, respectively.
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6. Conclusion
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The investigation that is described in this chapter has derived an offline model that simulates the system dynamics of the real MODICAS patient tracking procedure very well, independently from the operating point of the system. The model enables the developer to better understand the functional principle of the tracking procedure and to perform a specific tuning of its parameters in order to increase its overall dynamic performance. One model-based experiment has already delivered an improvement of the tracking control strategy. In the future, further experiments will show how the improvement of the localizer device, especially by means of noise reduction and a faster data aqcuistion, can enhance the overall dynamic performance of the tracking procedure.
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\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/6513.pdf",chapterXML:"https://mts.intechopen.com/source/xml/6513.xml",downloadPdfUrl:"/chapter/pdf-download/6513",previewPdfUrl:"/chapter/pdf-preview/6513",totalDownloads:3692,totalViews:203,totalCrossrefCites:0,totalDimensionsCites:2,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:58,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:null,dateReviewed:null,datePrePublished:null,datePublished:"January 1st 2010",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/6513",risUrl:"/chapter/ris/6513",book:{id:"3709",slug:"robot-surgery"},signatures:"Hans-Christian Schneider and Juergen Wahrburg",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The modiCAS surgical assistance robot",level:"1"},{id:"sec_3",title:"3. Real time tracking of patient’s movements by the robot",level:"1"},{id:"sec_4",title:"4. Simulation model describing the real time tracking procedure",level:"1"},{id:"sec_4_2",title:"4.1. Global model structure",level:"2"},{id:"sec_5_2",title:"4.2. Robot model",level:"2"},{id:"sec_6_2",title:"4.3. Localizer model",level:"2"},{id:"sec_7_2",title:"4.4. Model verification",level:"2"},{id:"sec_9",title:"5. Application example: model-based controller design",level:"1"},{id:"sec_10",title:"6. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBompos\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArtemiadis\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOikonomopoulos\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKyriakopoulos\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Modeling, full identification and control of the mitsubishi PA-10 robot arm. 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University of Siegen, Center for Sensor Systems (ZESS), Germany
University of Siegen, Center for Sensor Systems (ZESS), Germany
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1. Introduction
This chapter aims to provide an overview of the transdisciplinary work of the Neurosurgeon, Neuroanesthesiologist and Neuropsychologist before, during and after the resection of a neoplasm in eloquent areas with the patient conscious under the 3A anesthesia modality (asleep, awake, asleep). The diagnostic approach and the logistics to carry out this procedure and achieve better results will be shown.
At present there is growing evidence regarding the benefits of surgery in awake patients, with application in the treatment of epilepsy, abnormal movements and neurooncological surgery [1]. The benefits of awake craniotomy are increased lesion removal, with improved survival benefit, whilst minimizing damage to eloquent cortex and resulting postoperative neurological dysfunction. Other advantages include a shorter hospitalization time, hence reduced cost of care, and a decreased incidence of postoperative complications [2, 3]. This approach has allowed to achieve a higher degree of resection with less morbidity and a higher quality of life [2, 3].
1.1 History of brain surgery with awake patient
Throughout the history of neurosurgery it is known from archeological findings that therapeutic trepanation has existed since the Neolithic period between 8,000–500 BC, this type of treatment was performed for headaches, fractures, localized cranial deformity, mental changes, infections or seizures [4].
The earliest descriptions in the modern era of neurosurgery date back to descriptions in the treatment of epilepsy in the 17th century. However, the most identifiable antecedent dates back to the beginning of the last century with Penfield’s descriptions in the 1920s of intractable epilepsy surgery in awake patients and later in 1937 with the exposure of the intraoperative electrical stimulation technique used for the treatment of epileptogenic foci close to the language area [5, 6].
It was not until 1970 that the intraoperative cortical mapping technique began to be used for the resection of neoplastic lesions by Whitaker and Ojemann, who perfected the technique and published the first series that demonstrated the usefulness of this technique, describing it as safe, simple and adequately tolerated by most patients [5, 6, 7]. Later, in the last decade of the 20th century, Berger began to treat infiltrating neoplasms in eloquent cortical areas, improving the cortical mapping technique with the posterior publication of his experience [5, 8, 9]. Finally, in recent decades, new neuroanatomical studies and the popularization of the cortical mapping technique have led to a better understanding of the cortical and subcortical anatomy, improving the technique and prognosis of patients with infiltrating CNS lesions [10, 11].
For centuries there has been an incessant search to associate specific neurological functions with specific areas of the nervous system. At the beginning of the 19th century, explanatory models of functional neuroanatomy were built. The first to develop a model was Franz Joseph Gall (1776–1832) and his disciple Spurzheim. Dr. Gall is the founder of phrenology, based on the interpretation of the different neurological functions, on the basis that the greater development of a certain function resulted in hypertrophy of a specific brain region and that this hypertrophy conditioned a variation in the external configuration of the skull. This ability of the nervous system to “hypertrophy”, erroneously in the past, is now one of the main properties of the central nervous system used by modern radiology, such as the BOLD effect (increased blood supply to an area that is developing functional activity) or PET (increased glucose metabolism) [12, 13].
Walter Moxon (1836–1886) published the first cases that exposed the principle of hemispheric lateralization, associating the right hemiplegia with aphasia and, therefore, breaking the principle of hemispheric symmetry and locating language in the dominant left hemisphere. Later, Paul Broca presented the case of Monsieur Leborgne a patient suffering from septic gangrene in the lower limb. He was admitted to the Salpetriere hospital in Paris with a clinical presentation described by Broca as “expressive aphemia”, that is, he did not present facial motor deficit or comprehension problems, but the patient was unable to articulate words. An autopsy study identified the lesion in the posterior part of the lower left frontal gyrus. Pierre Marie (1853–1940), reexamined the brain of M. Leborgne, despite confirming the anatomical - functional association made by Broca 50 years earlier, he also concluded that the lesion was not limited to Broca’s area only, but it extended subcortically to the striatum and posterior to the angular gyrus [12, 13, 14].
Carl Wernicke in 1874 gave name and anatomical location to sensory aphasia that he located in the primary auditory cortex, in the posterior part of the superior left temporal gyrus. Decades later Theodore Meynert (1833–1892) was the first to associate auditory aphasia with the posterior part of the superior left temporal gyrus. Wernicke not only correlated the types of aphasia with different areas, but also established the term conduction aphasia (inability to repeat words) for those syndromes of disconnection between the sensory and motor areas of language, associated with the lesion of the arcuate fascicle (AF) [13, 15].
Geschwind succeeded in introducing one more level into the theory of language: the fundamental idea of networking and interconnection of the central nervous system. There are some basic Broca - Wernicke nodes and their main connection, which is the arcuate fascicle, but they do not work in isolation [16].
Damasio published the implication of the associative areas of the left medial frontal gyrus and the premotor area when performing tasks of understand words when related to animals, tools, or people. Also the implication of the inferotemporal cortex in the assimilation of the semantic concept of language, regardless of the stimulus pathway through which the word, visual (reading) or auditory information arrives, the precise implication of the dominant temporal pole in the memory-language association with the name of famous faces or places. He also characterized the difference between the pure primary auditory cortex in the transverse gyrus of Heschl and the posterior temporal area in T1 proper language, establishing the high regional cortical specialization for language understanding and he introduced the participation of the right hemisphere in the assimilation of concepts [17, 18].
1.2 Anatomy of brain eloquent areas
Once the historical review of the intraoperative cortical mapping has been carried out, it is important to emphasize that it is an evolving paradigm. Nowadays the vision of functions dependent on a specific anatomical cortical site has given way to a new dynamic and integrative paradigm with structural and functional connectivity and reciprocal influence, in this manner a lesion in a given site does not affect only one function, but the system as a whole [19, 20]. For this reason, pre-surgical functional studies are not superior to intraoperative mapping.
Although it is accepted that the mapping should be directed towards the area where the lesion is located, the wide anatomical and functional variability between individuals, limitations in presurgical neuroimaging, and functional modifications caused by the tumor must be considered [21, 22]. Usually, the evaluation of 8 main domains is accepted, which are adapted to the location of the lesion, activity of each patient and the evaluation of the benefit of a broad resection against the loss of functionality/neuroplasticity [20, 22]:
Movement.
Somatosensory function.
Visual Function.
Vestibular/auditory function.
Language (spontaneous, nominate, understand, repeat, read, write).
Left inferior frontal gyrus, left inferior temporal gyrus
SLF
Judgment, decision making, understanding
Left dominant prefrontal cortex, Left posterior temporal cortex.
Inferior occipitofrontal fasciculus
Selection, inhibition, attention
SMA, cingulum, frontal eye fields.
Subcallosal medialis fasciculus, head of the caudate nucleus
Table 1.
Cortical and subcortical structures involved in major brain functions as detected by direct cerebral stimulation.
SLF: superior longitudinal fasciculus.
SMA: supplementary motor area.
From: De Benedictis A, Duffau H. Brain hodotopy: From esoteric concept to practical surgical applications. Neurosurgery 2011;68:1709–23.
The cortical mapping must be adapted in each patient, according to location of the lesion. The following paragraphs review the main tasks and effects of cortical stimulation.
1.2.1 Frontal lobe
The main functions to evaluate correspond to the motor paradigm, which traditionally has an anatomical correlate in the primary motor cortex in the precentral gyrus, and surrounding subcortical regions, therefore it is necessary to map this area to avoid contralateral paresis or plegia. Corona radiata is considered the posterior subcortical limit of a frontal lesion resection. Cortical mapping is performed by asking the patient to perform movements while stimulating the specific area with respect to the Penfield homunculus, which will lead to its inhibition, or in a patient at rest the stimulation will cause involuntary movement [21, 22] (Vignette 1).
It is the most widely used technique in awake patient surgery to delimit essential brain regions for some functions such as movement and language. It consists of the administration of an electric current in milli-amperes directly on the cerebral cortex (authors recommend bipolar stimulation, short train, 1 ms duration and 200 Hz frequency, with 5-20 mA intensity) in order to cause depolarization of a group of neurons belonging to a cerebral system to produce a positive symptom (such as a muscle contraction) or negative (such as the arrest during number counting).
Thanks to this technique, the organization of the representation of the body in the cerebral cortex was described by the eminent neurosurgeon Wilder Penfield in the 1950s and later important contributions were made on the organization of language in the brain by George Ojemann.
Among the most important advantages is the speed with which a wide region of the cerebral cortex can be mapped, in cases where the neoplasm delimited in the cortex can be observed, the edges of the lesion can be delimited. In the same way, it is possible to stimulate subcortically in the white matter.
Among the most important limitations is the little time available to carry out a cognitive task. For example, it is ideal to explore the denomination since the electrical stimulus can be administered immediately after asking the patient for the name of an object represented in a slide (several seconds), however it would not be possible to administer an electrical stimulus during the elaboration of a narration (Figures 1–3).
Figure 1.
Cortical stimulation with bipolar.
Figure 2.
Use of cortical stimulation guided by navigation.
Figure 3.
Cortical stimulation using various contacts.
The supplementary motor cortex (SMA) is responsible for preparation, initiation, and monitoring movement, and it is located anterior to the cortical representation of the lower limb of precentral circumvolution. In the dominant hemisphere it exerts a function in the articulation of language, so its stimulation can cause alterations in the fluency of language when asking to name pictures. [22, 23].
The frontal premotor cortex (PMC) has a ventrolateral division responsible for the articulation of language, which when stimulated can cause anarthria; while the dorsolateral division is involved in the naming network, causing anomia when stimulated, this mainly in the dominant hemisphere. This location is where the intensity values of the stimulation are determined to obtain responses in the rest of the areas to explore [22, 23].
The cortex of the inferior and middle frontal gyri, when stimulated, causes impairment in writing.
Regarding the frontal subcortical mapping, these fasciculi are evaluated by counting, naming, and reading tasks, the main tracts to evaluate in this area are:
Superior Longitudinal Fasciculus (SLF): it has the cortical projections of the frontal, temporal and inferior parietal lobe. SLF stimulation through the arcuate fasciculus (AF), can cause problems in the production of language, memory alterations and phonemic paraphasia.
Subcallosal fasciculus: it links the frontomesial structures with the striatum, so its stimulation causes a decrease in fluency or difficulty in initiating language.
Anterior part of Inferior Frontooccipital fascicle (aIFOF): projects the orbitofrontal and dorsolateral prefrontal cortex with the temporooccipital cortex. aIFOF stimulation causes semantic paraphasia and failures in facial recognition. aIFOF represents the lower limit of resection of frontoorbital lesions [22, 23, 24].
Executive functions, working memory, attention, control, judgment and decision-making, functions related to perisylvian and prefrontal areas are also evaluated.
1.2.2 Parietal lobe
The primary somatosensory cortex is located posterior to the primary motor cortex and, if necessary, it is possible to resect it without significant alterations in the sensory function, since other association areas can supply its function. However, the thalamocortical radiation must be preserved, representing the anterior limit of resection of parietal lesions [22, 23, 24].
The cortical region of the inferior parietal lobe, the supramarginal and angular gyrus, affect language in the dominant hemisphere and spatial awareness in the non-dominant hemisphere. Writing and calculation tests should be done to avoid iatrogenic Gertsman’s syndrome. In the subcortical region of the dominant inferior parietal lobe (Geschwind territory), there are continuity of the pathways that communicate Broca’s area (inferior frontal cortex) with Wernicke’s area (posterior temporal cortex), the AF and SLF, therefore the stimulation of these areas can cause paraphasia and alteration in the production of language [22, 25].
1.2.3 Temporal lobe
In the temporal cortex, the main function to identify is language, especially in lesions of the dominant hemisphere. The posterior limit of a temporal pole resection is the arcuate fasciculus, which when stimulated causes paraphasia. Other temporal cortical and subcortical functions are visual recognition and dependent language, which is assessed with picture recognition. Likewise, temporary optic radiation should be evaluated in periventricular lesions in this region, in order to avoid postsurgical hemianopia [23].
1.2.4 Occipital lobe
The primary visual cortex is the main area to be explored, which when stimulated can produce phosphenes, blurred vision, visual hallucinations, and scotomas. Regarding the subcortical mapping, the final portion of the IFOF can produce alteration in the recognition and conceptualization of objects, so semantic paraphasia can be found [22, 23].
1.2.5 Insular lobe
The insular cortex and its corresponding subcortical tracts are considered unresectable, since they represent an important anatomical seat of essential functions of sensory, motor, limbic, vestibular and language integration. It is explored using a picture naming test [22, 26].
In a report, Ius et al., were able to identify sites considered unresectable after cortical mapping and resection of the lesion; in the dominant hemisphere the primary sensory and motor areas for the upper and lower extremities, the ventral premotor cortex, Wernicke’s area in the posterior part of the superior temporal gyrus, and the supramarginal and angular gyrus; while in the non-dominant hemisphere the primary motor and sensory cortex and the angular gyrus. In certain cases it was possible to excise the rest of the association areas under the principle of maximum resection without greatly affecting the function [20, 21, 22]. Likewise, regarding the tracts, the following were considered unresectable: the cortico-spinal tract, posterior limit in patients with frontal lesion; thalamic-cortical radiations, anterior limit in patients with parietal lesions; the stratum sagittale, medial border of temporo-parietal lesions; anterior part of IFOF and perisylvian network [21, 22].
1.3 Brain lesions affecting the eloquent areas and surgical criteria
In general, neoplastic intracranial lesions can displace or invade brain structures. The first group of lesions are not usually candidates for awake resection, since the symptoms are produced by the effect of mass on the cortex and tracts, but their resection does not involve functional areas. Unlike the second group of neoplasms that can infiltrate or even originate in functional areas, and whose resection without the appropriate quality of life approach, can have unacceptable consequences for the functioning of patients. Also, since the patient should be comfortable as much as possible for resection of the lesions, the awake and cortical mapping approaches usually involve convexity or superficial, intra-axial, supratentorial lesions [1, 27].
In a review of several reported series of awake cortical mapping, gliomas are the neoplasms that are most frequently approached by this technique, up to 60%. High-grade astrocytomas such as OMS GIV glioblastoma is the most frequent glioma reported, followed by oligodendrogliomas, oligoastrocytomas, and low-grade astrocytomas [2, 28, 29]. The second group in frequency are brain metastases, mainly pulmonary and mammary origin. Finally, non-neoplastic lesions such as cavernous angiomas are usually reported as accessible lesions using this technique [30].
Although it is true that all the lesions described in the previous paragraph benefit from a wide resection, at present special emphasis has been placed in low-grade gliomas since these are lesions that usually occur in young adults, and it migrates through white matter tracts at an average rate of 4 mm/year [23, 31]. This raises new paradigms in which a supramarginal resection has been proposed even at the cost of function, hoping that brain plasticity in young patients improves the prognosis and quality of life in the long term [32].
1.3.1 Surgical criteria
The main criteria that are considered in neurosurgery to determine that a patient is considered for this type of procedure can be consulted in Figure 4 in the form of a flow chart. Some of the most important criteria will be mentioned below according to the purpose of this chapter:
The lesion should be located intra-axial (typical of the brain parenchyma), in a brain region that implies a high risk of post-surgical neurological and/or cognitive alterations. Generally, cortical and/or subcortical sensorimotor and periinsular regions of the dominant hemisphere. However, other “highly specialized areas” should be considered according to the profession of each patient.
In relation to the radiological characteristics of the tumor, ideally with little cerebral edema, without significant midline deviation.
Degree of malignancy. Previously it was considered that the tumor should be low grade (histologically) since having a good survival prognosis, the benefit of keeping it neurologically intact was essential However, nowadays it is currently considered that it should also for patients with a high-grade, to promote quality of life.
Patient can decide to accept the procedure and agree to collaborate once he knows the type of surgery that is proposed.
Patient with no history of anxiety or impulsivity disorder because these may be exacerbated during surgery (e.g. refusing to cooperate or presenting psychogenic symptoms that make evaluation difficult) (Table 2).
Figure 4.
Diagram showing the flow of neurosurgical conditions that must be considered to determine that a patient is a candidate for awake surgery (red line). Patient admitted to neurosurgery, from the outpatient or emergency department with an intra-axial lesion, located in a highly specialized area. Candidate for structural, functional and tractography MRI. Neuropsychological assessment confirmed the possibility of surgery with a conscious patient. Surgery is scheduled with a navigation method for resection of the lesion.
Attempt to improve function w/ up to 5 days of preoperative high-dose steroids w/ or w/o diuretics
Tumor location presumed to be w/in functional cortical or subcortical pathways on preop imaging
The decision to offer surgery is not made based on preop anatomical or functional imaging (attempt is always made to map, identify, & preserve functional sites).
Table 2.
Relative contraindications and solutions for awake craniotomy patients.
Motor function <2/5 or baseline naming/reading errors.
BMI = body mass index; IV = intravenous; MEG = magnetoencephalography; MSI = magnetic source imaging.
From: Hervey-Jumper SL, Li J, Lau D, Molinaro AM, Perry DW, Meng L, et al. Awake craniotomy to maximize glioma resection: Methods and technical nuances over a 27-year period. J Neurosurg 2015;123:325–39.
1.4 Pre-operative evaluation
Once the patient has been selected for resection of the lesion with cortical mapping, extension studies should be carried out to bring us more evidence regarding the patient and their environment through neuropsychological and neuro-anesthesiology assessment. In addition, to plan the intraoperative mapping, it is advisable to perform:
Diffusion tensor tractography (DTI): identifies the main tracts of white fibers (corticospinal, superior longitudinal fasciculus, arcuate fasciculus, uncinate fasciculus, inferior orbitofrontal fasciculus, optic pathways) their location and infiltration or displace. However, the variability between imaging and the effect of medical treatment on the injury and associated vasogenic edema must be taken into consideration.
Functional MRI: it helps to locate functional cortical areas through dependent sequences of blood oxygenation, which detects the increase in cerebral perfusion to certain areas when specific tasks are performed. The most studied paradigms are motor, sensory and speech (Vignette 2).
Vignette 2. Functional Magnetic Resonance (fMRI)
The functional Magnetic Resonance images are based on the changes in the oxygen levels in the blood related to an activity by the subject. It is an indirect measure of brain functionality since the equipment detects changes in signal intensity caused by vascular changes (demand for oxygen supply through the blood). Since the construction of the images depends on the use of complex mathematical algorithms, it is not possible to completely eliminate the noise sources that may occur, causing false positives, that is, activations in some brain region that are not real. In the same way, false positives can occur due to the pathology of the brain tissue itself due to the pathological vasculature.
It is currently one of the most common methods in cognitive neurosciences due to its safety in healthy subjects.
Figure 5 shows motor paradigm during evaluation of a patient with a supratentorial glioma.
Figure 5.
Functional MRI with motor paradigm.
Other functional extension studies such as positron emission tomography (PET) or magnetoencephalography allow planning the procedure but none of them is superior to intraoperative cortical mapping, which is considered the gold standard.
1.5 Anesthetic management
1.5.1 Neuroanesthetic perioperative management
Benefits of awake craniotomy are greater resection of the lesion, with improvement in survival, while the damage to the eloquent cortex, which generates postoperative neurological dysfunction, is minimized. Other advantages include shorter hospitalization times, hence a reduction in care costs, and a decrease in the incidence of postoperative complications.
The term “awake craniotomy” is misleading as the patient is not fully awake during the entire procedure. The most painful moments of surgery require different levels of sedation or anesthesia, nonetheless, patient is fully awake while mapping or during resection [33].
1.5.2 Preoperative evaluation
A very important aspect in an awake craniotomy is the adequate selection and full preparation of the patient by a multidisciplinary team in order to avoid intraoperative failures [34].
All patients should have consultations with the neurosurgeon and neuroanesthesiologist to assess whether the patient is a good candidate for this technique (seeTable 3) and to prepare the patient for the procedure. This includes a complete evaluation of patient’s comorbidities, which must be optimized before surgery, in or Patients in whom a difficult airway is anticipated may have problems during the intraoperative period that possess the neuroanesthesiologist to a very difficult airway scenario. Children are not psychologically fit to undergo this procedure although individual development of each child must be considered.
Absolute
Patient refusal Inability to lay still for any length of time Inability to co-operate, for example confusion Mental retardation Anticipated difficult intubation Obstructive sleep apnea Children <10 years
Relative
Patient cough Learning difficulties Inability to lay flat Patient anxiety Language barriers Obese patients
Table 3.
Anesthetic contraindications.
Preoperative evaluation includes getting detailed information from the patient, in turn the patient must know what to expect and know the risks inherent to anesthesia. Usually this includes verbal and written informed consent [34, 35].
Pre-operative consultations provide an invaluable opportunity for the multidisciplinary team to create a rapport with the patient and therefore encourage trust.
1.5.3 Operating room preparation
The layout of the operating room and the position of the patient must be taken into account. The ability to communicate with the patient must be maintained at all times and access to the patient during adverse events is of equal importance.
As in every surgery, the operating table should be as comfortable as possible, since the patient is going to be lying in the same position for several hours. The operating room temperature should be comfortable for the patient, and the number of people should be minimized to reduce unnecessary noise and reduce patient anxiety [36].
The position of the patient is determined by the location of the lesion. (Figure 6) This is usually a lateral or supine position, in the case of occipital lesions and evaluation of the visual cortex, a sitting position may be used. In either position, it’s important that when patient is fully awake during mapping, he can see and communicate with the neuroanesthesiologist or neuropsychologist. Sterile drapes used should not invade the patient’s face, as this may cause claustrophobia and difficulty in communicating [37].
Figure 6.
Position of the patient and the evaluator during the surgical procedure to carry out the neuropsychological and movement evaluation.
1.5.4 Anesthetic generalities
The choice of the anesthetic agent even within a preferred anesthetic technique varies, but the general principles are common to all of them; the need to maximize patient comfort, prevention of nausea and vomiting that may increase intracranial pressure, the need for hemodynamic stability, and the use of short-acting drugs that allow acute control of the patient’s level of consciousness.
Premedication is not common, but reflux prophylaxis should be considered, patients should continue their prescribed medication such as steroids, antiepileptic drugs, or antihypertensives. Prophylactic antibiotics and usually one or more antiemetics are administered in every patient before the incision. The most common options are ondansetron and dexamethasone. Dexamethasone can also be used to diminish brain edema during the operation.
Standard anesthetic monitoring is used. Depth of anesthesia monitors, for example Bispectral Index Monitoring (BIS™), are sometimes used to reduce the dose of anesthetic agents administered and thus time required for patient emergence and cortical mapping cooperation [37, 38].
Capnography under general anesthesia is considered basic monitoring, but carbon dioxide monitoring for sedated or awake patients during mapping is also a common practice. Although carbon dioxide levels may be inaccurate, it is used to confirm ventilation [39].
A large-bore intravenous access is obtained and most neuroanesthesiologist place also an arterial line, usually sedated or asleep. The use of other forms of monitoring is variable.
1.5.5 Anesthetic techniques
There is not a recognized consensus on the best anesthetic approach for awake craniotomy. This is because neuroanesthesiologists vary the technique depending on neurosurgeon’s preferences, pathology, duration of the surgery and patient’s factors.
There are two dominant anesthetic approaches to solving this problem: monitored anesthetic care (MAC) and asleep-awake-asleep (AAA).
The goal of the MAC approach is to decrease the sedative dose to avoid an abrupt transition from sleep to awakening, which can lead to hypoactive or hyperactive delirium upon emergence and to decrease the reliability of mapping. MAC technique for awake craniotomy involves spontaneous ventilation and low doses of sedative drugs [38].
The AAA technique involves induction of general anesthesia and control of the airway with a supraglottic device such as laryngeal mask airway (LMA) or intubation. When neurocognitive testing and intraoperative mapping need to be started, anesthetic drugs are reduced or stopped, and the device is removed from the airway. Once resection of the lesion is complete, return to general anesthesia and reintroduction of the airway device is done. Advantages of this technique include the ability to control ventilation and thus control carbon dioxide concentrations and prevent airway obstruction and hypoventilation. It also facilitates a greater anesthetic depth during the most painful moments of surgery. Anesthetic drugs used for this technique are varied, but propofol and remifentanil TCI are the most common, followed by the use of a volatile anesthetic and remifentanil infusion. The use of dexmedetomidine has also been reported with this technique, and it’s generally used during the awake stage of surgery and closure [39].
1.5.6 Scalp block
The cornerstone of awake craniotomy analgesia is regional scalp block along with infiltration of the incision line. A scalp block also provides hemodynamic stability and decreases the stress response to painful stimuli [40].
The scalp block technique includes infiltration of local anesthetic into seven nerves on each side. This is an anatomical block and not just a ring block. A ring block will require large volumes of local anesthetic, increase the risk of toxicity, and will not provide deep anesthesia to the temporal fascia.
Most neuroanesthesiologist place a bilateral scalp block before pinning of the head with Mayfield skull clamp. Occasionally, a scalp blocker is not applied and relies on local anesthetic infiltration by the surgeon.
The total dose of local anesthetic with and without epinephrine must be calculated individually for each patient. Studies have shown that the rise in plasma concentration of levobupivacaine and ropivacaine is faster compared to other local anesthetics and similar in all patients. Despite the quick rise in plasma levels, there were no signs of cardiovascular or central nervous system toxicity. The use of bupivacaine, levobupivacaine, and ropivacaine in varying concentrations with and without epinephrine has been described for use in a blockage of the scalp. The addition of epinephrine, usually 1: 200,000, increases the total amount of local anesthetic that can be used, decreases localized bleeding, and maximizes duration. However, systemic absorption may cause tachycardia and hypertension, and intraarterial injection into the superficial temporal artery is possible when the auriculotemporal nerve is blocked [37].
1.5.7 Adverse events
Awake craniotomy is generally a well-tolerated procedure with a low conversion rate to general anesthesia and a low complication rate. One of the most common complications is intolerance of the patient to the procedure, often due to urinary catheter or prolonged positioning and intraoperative seizures.
Seizures, focal or generalized, are more likely to occur during cortical mapping. The frequency of seizures during awake craniotomy ranges widely from 2.9–54%. These are treated by irrigating the brain tissue with ice-cold saline, they usually stop with this treatment, but sometimes benzodiazepines, antiepileptic drugs or re-sedation with airway control are required [41].
The efficacy of prevention of intraoperative seizures with anticonvulsants remains doubtful. The latest systematic review on this topic revealed no benefit of prophylaxis. However, it should be noted that most of seizure prevention trials are based on the use of phenytoin or valproate. On the other hand, there are new data that support the superiority of levetiracetam in the prophylaxis of seizures. However, there are insufficient data to recommend its routine use in awake craniotomy.
An emergency plan for airway control must be in place at all times and this can be challenging as the patient’s head is fixed on the clamp and often away from the ventilator. Options include insertion of an LMA which may be easier than endotracheal intubation.
1.5.8 Closure and postoperative
Once resection is complete, patient may be re-sedated or re-anesthetized with reattachment of the airway device, even if in the lateral position. Dura, bone flap, and scalp are then closed, pins are removed, and patient is awakened.
If remifentanil has been used, it can be given at low infusion rates to aid for a “soft” awakening and prevent coughing.
It is imperative that close neurological monitoring continues as postoperative hematomas may develop, especially in the first 6 h after operating. This may require an urgent evacuation of the clot.
After scalp block has worn off, systemic pain relief is used. The use of postoperative pain relief can be decreased in patients who have received a scalp block. Regular paracetamol and opioids are used.
1.6 Neuropsychological management
Some generalities of intraoperative neuropsychological evaluation will be mentioned in the light of new neurocognitive technological and theoretical tools that allow us to carry out current forms of evaluation, always outlined based on the objectives of the surgical plan of the transdisciplinary group of the treating physician, as well as the type of tumor, location and extension.
The selection of the methodology for the intraoperative neuropsychological evaluation is described in detail in accordance with the current literature on a recent vision of Functional Neurosurgery in brain tumors called hodology [19], which implies a radical change to the classical view on a rigid and exclusively cortical cerebral organization of brain functions. (Vignette 3) The advances that have occurred in recent decades on neurocognitive aspects in patients with brain tumors allow the more specific evaluation of some aspects of language, for example the name by visual confrontation has been a very important way of assessing an aspect of language in the operating room [9] but until recently attention has been paid to the type of stimuli that are presented and how to do it, that is, we currently know that the findings may be different if they are presented for the naming, an image or drawing in black and white compared to a color image with three-dimensional properties, in addition to the control of psycholinguistic variables of the words [13]. The same can be mentioned in other cognitive domains, for example the advance in the knowledge of the participation of subcortical structures in cognition, the participation of the right hemisphere in language at the narrative level, social cognition, brain reorganization in the recovery process, participation of the insula in cognitive aspects, to name a few [41].
Vignette 3 - Brain Hodotopy
This term refers to a current vision in functional neurosurgery in which the classic trend of localize functions in the cerebral cortex is changed by a concept called hodological mechanism (from the Greek hodos, path or path) related to the cognitive alteration caused by affection in anatomical connectivity rather than a lesion in the cerebral cortex.
This approach conceives the Central Nervous System as a comprehensive system integrated by a plastic network made up of functional cortical epicenters connected by short and long fibers of white matter. Thus, brain functions are the result of the confluence of parallel information pathways, dynamically modulated in a widely distributed, interactive and multimodal circuit.
This view is of great relevance, especially in brain tumor neurosurgery due to the brain plasticity that is induced by the neoplasm itself. This phenomenon makes the dissociation between anatomy and functional delimitation especially valid, that is, to determine anatomically an area (for example the precentral gyrus) does not guarantee that it functionally corresponds to motor regions. This new perspective opens the possibility of contemplating the performance of surgical procedures in regions that were previously considered inoperable. Broca’s area is an example of this new vision, since if it is considered inoperable, different brain mapping techniques such as cortical electrical stimulation can currently be used to functionally delimit this region through naming tasks. Broca’s area is also a good example to show the brain plasticity that the hodological approach considers, since we frequently observe neoplasms in these regions with a patient without deficit (dynamic, not rigid system), and it is well known that in order to presents an alteration compatible with Broca’s aphasia, the lesion must include cortical and subcortical regions (cortical epicenters and connectome), since a lesion limited only to the cerebral cortex corresponding to Brodmann’s area 44 and 45 is associated with a transitory alteration less severe.
Transoperatively evaluating a cognitive domain with all the theoretical complexity that we currently have can take a long time, bringing an apparent contradiction, since on the one hand we require time to assess details of the domains, however, during surgical procedures with the patient awake, only they have several seconds and in some cases minutes. This leads to apparently unrelated cognitive areas that will be evident in the postoperative period. To exemplify this, we can take the case of the famous patient HM, one of the best known cases in the history of modern neurosciences who was operated awake during the bilateral resection of hippocampal structures in 1953. At that time, it was only considered important to explore the understanding and expression of language, without considering the exploration of other cognitive domains, resulting in the tragic history of memory loss that we all know. Without devaluing the merit of surgery in the context of the time, this story teaches us that it is essential to carry out a broader neuropsychological evaluation in terms of cognitive domains, apparently little related to the intervened brain region, so that the consideration of the activities to perform during the intraoperative is essential in order to optimize the time and tasks to be performed.
Among the most important neuropsychological criteria is that the patient wishes to cooperate and his neurological and psychological condition allows it, that is, the patient must understand why the suggestion of this surgery modality so that he openly expresses that he wants awake modality, knowing that it can be stressful to a certain extent and that your participation is essential. A second important criterion is not to present alterations that may obstruct the intraoperative neuropsychological evaluation. In this sense, the patient could find conditions that allow him to have a functional daily life, however, it may be that for the surgical procedure it is not suitable, for example a tumor in prefrontal regions that could affect uninhibited behavior. This could be dangerous because the integrity of the patient could be compromised by refusing to participate during surgery. Another example could be the difficulty in understanding long sentences or marked slowness when carrying out the instructions. These examples show that, even though the patient understands the importance of the procedure and shows the willingness to cooperate, it should be considered, since in the last example it could be determined that it would be enough to be able to carry out the monitoring of gross motor aspects, so it could be done.
An important aspect is to know, through anxiety, depression and impulsivity scales, the degree that the patient can manifest in the face of stress, since the procedure can facilitate the appearance of behaviors that could hardly be observed in daily life.
In our experience, awake surgery involves a series of stages prior to the intraoperative that the patient must undergo to guarantee a greater chance of success. That is, if it is true that success depends largely on what happens in the operating room, it is also true that a lot has to do with the preparation of the patient, the collection of neuropsychological and psychological data, and in some cases the family dynamics before the surgery, as it must be remembered that patient participation is essential, so that an inadequate preparation (eg, lack of understanding of the purpose of the procedure) could turn into limited cooperation and vulnerable to fatigue due to the small discomforts that could present.
In the same way, follow-up is important to guide the family and the patient about neuropsychological or personality changes that may occur, some of them may require neuropsychological intervention or orientation to primary caregivers.
The entire conventional neuropsychological clinical interview is conducted paying attention to traits or probable personality disorders, how to manage stress in the daily life and impulse management. It should be remembered that surgery can represent a time of stress in which the patient can behave differently from the way they do it in their daily life (explain with appropriate psychological terms that it can be psychologically unstructured), in addition to the use of medications that they could contribute for that moment. (If you are in stress, you can request to be put to sleep or decide not to cooperate, making the procedure considerably more difficult).
A conventional neuropsychological evaluation is performed. In brain tumors, large batteries are used in terms of functions, e.g. The Comprehensive Neuropsychological Exploration Program Test Barcelona completes and complementary tests.
One of the purposes is to detect qualitatively and quantitatively. All this to detect obvious or subtle alterations that the neoplasm is already causing and think about the possibility that these alterations are highlighted.
Psychological approach in which the patient’s real expectations and fantasies must be detected. Anxiety and depression must be identified. Follow-up is encouraged for the next stages, gives an overview of what might happen if the tumor is malignant or non-malignant. This stage is mixed with the Psychological intervention and the intervention plan must begin here.
Other aspects that influence this stage are:
the carving explanation of the procedure, beginning, end, when waking up, when sleeping, when to sedate it, activities to perform, activities to perform, possible discomfort, procedure simulation, stereotactic frame simulation. As far as possible, visit the operating room from the outside, explanation of a video of a patient with a similar tumor.
1.6.1 Family involvement
This gives you a lot of neuropsychological material to ask questions during surgery, e.g. If so, a description of the coffee harvest can already be requested (since he is involved in the process in his place of origin). This constitutes a great deal of material to use in assessing spontaneous language.
Activities are designed according to the neuropsychological profile and the surgical plan. This stage can be better understood in the section on the intraoperative neuropsychological evaluation plan.
Ecological evaluation plan, what the patient requires for her daily life.
Neuropsychological rehabilitation and orientation to the family on apparently permanent and transitory alterations, including personality changes.
General diagram (timeline) of the transdisciplinary treatment and location of the intraoperative neuropsychological evaluation. The steps prior to the neuropsychological assessment represented by interconnected circles represent the independence of each step, but the close relationship between them. CH: Clinical History, Pre-NP: Preoperative Neuropsychological Evaluation, PE: Psychoeducation, Inter Psicol - Psychological Intervention, Post: Postoperative neuropsychological follow-up, Rehab: Neuropsychological rehabilitation.
2. Conclusions
The most important objective of this surgical modality is the cognitive preservation and neurological function of the patient and at the same time achieving the greatest amount of tumor resection, that is, the removal of the greatest amount of brain tumor with the least amount of sequelae. This is especially valid for those patients who have a low-grade tumor with an adequate prognosis for life, recently also for those with a tumor with a higher grade of malignancy that will limit survival to several months. In both cases, the amount of pathological tissue that can be removed is of vital importance since the success of the rest of the complementary postsurgical treatments such as radio or chemotherapy depends largely on this.
The most serious intra-surgical complications include seizures, respiratory depression, air embolism, cerebral edema, and the cardiac trigeminal reflex. The total reported complication rate is about 16.5%, and in 6.4% of patients it is not possible to complete the mapping procedure.
The main causes of failure are the appearance of seizures and the loss of cooperation of the patient due to severe drowsiness, agitation, or the development of mixed dysphasia. Failed craniotomies are associated with a lower incidence of gross total resections, greater speech impairment after the procedure, and a longer hospital stay.
The application of awake craniotomy has continually evolved. The key to the success of this procedure is to pay attention to each of the components, such as careful patient selection, prior psychological preparation, building a solid relationship, ensuring the solid position of the patient, optimal regional anesthesia, the correct selection of agents and anesthetic technique, preparation and timely management of crises, and constant communication between group members.
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At present there is growing evidence regarding the benefits of surgery in awake patients, with application in the treatment of epilepsy, abnormal movements and oncological surgery. The benefits of awake craniotomy are increased lesion removal, with improved survival benefit, whilst minimizing damage to eloquent cortex and resulting postoperative neurological dysfunction. Other advantages include a shorter hospitalization time, hence reduced cost of care, and a decreased incidence of postoperative complications. This approach has allowed to achieve a higher degree of resection with less morbidity and a higher quality of life.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74982",risUrl:"/chapter/ris/74982",signatures:"José Luis Navarro-Olvera, Gustavo Parra-Romero, Stephani Dalila Heres-Becerril, David Trejo-Martínez, José D. 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Introduction",level:"1"},{id:"sec_1_2",title:"1.1 History of brain surgery with awake patient",level:"2"},{id:"sec_2_2",title:"1.2 Anatomy of brain eloquent areas",level:"2"},{id:"sec_2_3",title:"1.2.1 Frontal lobe",level:"3"},{id:"sec_3_3",title:"1.2.2 Parietal lobe",level:"3"},{id:"sec_4_3",title:"1.2.3 Temporal lobe",level:"3"},{id:"sec_5_3",title:"1.2.4 Occipital lobe",level:"3"},{id:"sec_6_3",title:"1.2.5 Insular lobe",level:"3"},{id:"sec_8_2",title:"1.3 Brain lesions affecting the eloquent areas and surgical criteria",level:"2"},{id:"sec_8_3",title:"Table 2.",level:"3"},{id:"sec_10_2",title:"1.4 Pre-operative evaluation",level:"2"},{id:"sec_11_2",title:"1.5 Anesthetic management",level:"2"},{id:"sec_11_3",title:"1.5.1 Neuroanesthetic perioperative management",level:"3"},{id:"sec_12_3",title:"Table 3.",level:"3"},{id:"sec_13_3",title:"1.5.3 Operating room preparation",level:"3"},{id:"sec_14_3",title:"1.5.4 Anesthetic generalities",level:"3"},{id:"sec_15_3",title:"1.5.5 Anesthetic techniques",level:"3"},{id:"sec_16_3",title:"1.5.6 Scalp block",level:"3"},{id:"sec_17_3",title:"1.5.7 Adverse events",level:"3"},{id:"sec_18_3",title:"1.5.8 Closure and postoperative",level:"3"},{id:"sec_20_2",title:"1.6 Neuropsychological management",level:"2"},{id:"sec_20_3",title:"1.6.1 Family involvement",level:"3"},{id:"sec_23",title:"2. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Ibrahim GM, Bernstein M. Awake craniotomy for supratentorial gliomas: why, when and how? CNS Oncol 2012;1:71-83. https://doi.org/10.2217/cns.12.1.'},{id:"B2",body:'Sacko O, Lauwers-Cances V, Brauge D, Sesay M, Brenner A, Roux FE. Awake craniotomy vs surgery under general anesthesia for resection of supratentorial lesions. Neurosurgery 2011;68:1192-8. https://doi.org/10.1227/NEU.0b013e31820c02a3.'},{id:"B3",body:'Lu VM, Phan K, Rovin RA. Comparison of operative outcomes of eloquent glioma resection performed under awake versus general anesthesia: A systematic review and meta-analysis. Clin Neurol Neurosurg 2018;169:121-7. https://doi.org/10.1016/j.clineuro.2018.04.011.'},{id:"B4",body:'Bulsara KR, Johnson J, Villavicencio AT. Improvements in brain tumor surgery: the modern history of awake craniotomies. Neurosurg Focus 2005;18:5-7. https://doi.org/10.3171/foc.2005.18.4.6.'},{id:"B5",body:'Kobyakov GL, Lubnin AY, Kulikov AS, Gavrilov AG, Goryaynov SA, Poddubskiy AA, et al. Awake craniotomy. Zh Vopr Neirokhir Im N N Burdenko 2016;80:107-16. https://doi.org/10.17116/engneiro201680188-96.'},{id:"B6",body:'July J, Manninen P, Lai J, Yao Z, Bernstein M. The history of awake craniotomy for brain tumor and its spread into Asia. Surg Neurol 2009;71:621-4. https://doi.org/10.1016/j.surneu.2007.12.022.'},{id:"B7",body:'Surbeck W, Hildebrandt G, Duffau H. The evolution of brain surgery on awake patients. Acta Neurochir (Wien) 2015;157:77-84. https://doi.org/10.1007/s00701-014-2249-8.'},{id:"B8",body:'De Witt Hamer PC, Robles SG, Zwinderman AH, Duffau H, Berger MS. Impact of intraoperative stimulation brain mapping on glioma surgery outcome: A meta-analysis. J Clin Oncol 2012;30:2559-65. https://doi.org/10.1200/JCO.2011.38.4818.'},{id:"B9",body:'Haglund M, Berger MS, Shamseldin M, Lettich E, Ojemann G. Cortical Localization of Temporal Lobe Language Sites in Patients with Gliomas. Clinical Study. Neurosurgery 1994;34:1689-99.'},{id:"B10",body:'Duffau H. Contribution of cortical and subcortical electrostimulation in brain glioma surgery: Methodological and functional considerations. Neurophysiol Clin 2007;37:373-82. https://doi.org/10.1016/j.neucli.2007.09.003.'},{id:"B11",body:'Duffau H. Stimulation Mapping of Myelinated Tracts in Awake Patients. Brain Plast 2016;2:99-113. https://doi.org/10.3233/bpl-160027.'},{id:"B12",body:'Buckingham HW. The Marc Dax (1770-1837)/Paul Broca (1824-1880) controversy over priority in science: Left hemisphere specificity for seat of articulate language and for lesions that cause aphemia. Clin Linguist Phonetics 2006;20:613-9. https://doi.org/10.1080/02699200500266703.'},{id:"B13",body:'Tate MC, Herbet G, Moritz-Gasser S, Tate JE, Duffau H. Probabilistic map of critical functional regions of the human cerebral cortex: Broca’s area revisited. Brain 2014;137:2773-82. https://doi.org/10.1093/brain/awu168.'},{id:"B14",body:'Iwata M. Anatomical Error of Pierre Marie’s “zone Lenticulaire.” Front Neurol Neurosci 2019;44:23-9. https://doi.org/10.1159/000494948.'},{id:"B15",body:'Rahimpour S, Haglund MM, Friedman AH, Duffau H. History of awake mapping and speech and language localization: From modules to networks. Neurosurg Focus 2019;47:7-12. https://doi.org/10.3171/2019.7.FOCUS19347.'},{id:"B16",body:'Nasios G, Dardiotis E, Messinis L. From Broca and Wernicke to the Neuromodulation Era: Insights of Brain Language Networks for Neurorehabilitation. Behav Neurol 2019:1-10. https://doi.org/10.1155/2019/9894571.'},{id:"B17",body:'Damasio AR. Brain and language: what a difference a decade makes. Curr Opin Neurol 1997;10:177-8.'},{id:"B18",body:'Damasio H, Grabowski TJ, Tranel D, Ponto LLB, Hichwa RD, Damasio AR. Neural correlates of naming actions and of naming spatial relations. Neuroimage 2001;13:1053-64. https://doi.org/10.1006/nimg.2001.0775.'},{id:"B19",body:'De Benedictis A, Duffau H. Brain hodotopy: From esoteric concept to practical surgical applications. Neurosurgery 2011;68:1709-23. https://doi.org/10.1227/NEU.0b013e3182124690.'},{id:"B20",body:'Duffau H. Hodotopy, neuroplasticity and diffuse gliomas. Neurochirurgie 2017;63:259-65. https://doi.org/10.1016/j.neuchi.2016.12.001.'},{id:"B21",body:'Ius T, Angelini E, Thiebaut de Schotten M, Mandonnet E, Duffau H. Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of WHO grade II gliomas: Towards a “minimal common brain.” Neuroimage 2011;56:992-1000. https://doi.org/10.1016/j.neuroimage.2011.03.022.'},{id:"B22",body:'Coello AF, Moritz-Gasser S, Martino J, Martinoni M, Matsuda R, Duffau H. Selection of intraoperative tasks for awake mapping based on relationships between tumor location and functional networks: A review. J Neurosurg 2013;119:1380-94. https://doi.org/10.3171/2013.6.JNS122470.'},{id:"B23",body:'Duffau H. New concepts in surgery of WHO grade II gliomas: Functional brain mapping, connectionism and plasticity - A review. J Neurooncol 2006;79:77-115. https://doi.org/10.1007/s11060-005-9109-6.'},{id:"B24",body:'Duffau H. Stimulation mapping of white matter tracts to study brain functional connectivity. Nat Rev Neurol 2015;11:255-65. https://doi.org/10.1038/nrneurol.2015.51.'},{id:"B25",body:'Vanacôr CN, Isolan GR, Yu YH, Telles JPM, Oberman DZ, Rabelo NN, et al. Microsurgical anatomy of language. Clin Anat 2020:1-15. https://doi.org/10.1002/ca.23681.'},{id:"B26",body:'Duffau H, Capelle L, Lopes M, Faillot T, Sichez JP, Fohanno D. The insular lobe: Physiopathological and surgical considerations. Neurosurgery 2000;47:801-11. https://doi.org/10.1097/00006123-200010000-00001.'},{id:"B27",body:'Dziedzic T, Bernstein M. Awake craniotomy for brain tumor: Indications, technique and benefits. Expert Rev Neurother 2014;14:1405-15. https://doi.org/10.1586/14737175.2014.979793.'},{id:"B28",body:'Brown T, Shah AH, Bregy A, Shah NH, Thambuswamy M, Barbarite E, et al. Awake Craniotomy for Brain Tumor Resection. J Neurosurg Anesthesiol 2013;25:240-7. https://doi.org/10.1097/ana.0b013e318290c230.'},{id:"B29",body:'Hervey-Jumper SL, Li J, Lau D, Molinaro AM, Perry DW, Meng L, et al. Awake craniotomy to maximize glioma resection: Methods and technical nuances over a 27-year period. J Neurosurg 2015;123:325-39. https://doi.org/10.3171/2014.10.JNS141520.'},{id:"B30",body:'Chua TH, See AAQ, Ang BT, King NKK. Awake Craniotomy for Resection of Brain Metastases: A Systematic Review. World Neurosurg 2018;120:e1128-35. https://doi.org/10.1016/j.wneu.2018.08.243.'},{id:"B31",body:'Duffau H. Diffuse low-grade glioma, oncological outcome and quality of life: A surgical perspective. Curr Opin Oncol 2018;30:383-9. https://doi.org/10.1097/CCO.0000000000000483.'},{id:"B32",body:'Duffau H. Higher-Order Surgical Questions for Diffuse Low-Grade Gliomas: Supramaximal Resection, Neuroplasticity, and Screening. Neurosurg Clin N Am 2019;30:119-28. https://doi.org/10.1016/j.nec.2018.08.009.'},{id:"B33",body:'Akay A, Islekel S. Awake craniotomy procedure: Its effects on neurological morbidity and recommendations. Turk Neurosurg 2018;28:186-92. https://doi.org/10.5137/1019-5149.JTN.19391-16.1.'},{id:"B34",body:'Kulikov A, Lubnin A. Anesthesia for awake craniotomy. Curr Opin Anaesthesiol 2018;31:506-10. https://doi.org/10.1097/ACO.0000000000000625.'},{id:"B35",body:'Eseonu CI, ReFaey K, Garcia O, John A, Quiñones-Hinojosa A, Tripathi P. Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques. World Neurosurg 2017;104:679-86. https://doi.org/10.1016/j.wneu.2017.05.053.'},{id:"B36",body:'Osborn I, Sebeo J. “Scalp block” during craniotomy: A classic technique revisited. J Neurosurg Anesthesiol 2010;22:187-94. https://doi.org/10.1097/ANA.0b013e3181d48846.'},{id:"B37",body:'Özlü O. Anaesthesiologist’s approach to awake craniotomy. Turk Anesteziyoloji ve Reanimasyon Dern Derg 2018;46:250-6. https://doi.org/10.5152/TJAR.2018.56255.'},{id:"B38",body:'Stevanovic A, Rossaint R, Veldeman M, Bilotta F, Coburn M. Anaesthesia management for awake craniotomy: Systematic review and meta-analysis. PLoS One 2016;11:12-23. https://doi.org/10.1371/journal.pone.0156448.'},{id:"B39",body:'Jones H, Smith M. Awake craniotomy. Contin Educ Anaesthesia, Crit Care Pain 2004;4:189-92. https://doi.org/10.1093/bjaceaccp/mkh051.'},{id:"B40",body:'Hill CS, Severgnini F, McKintosh E. How I do it: Awake craniotomy. Acta Neurochir (Wien) 2017;159:173-6. https://doi.org/10.1007/s00701-016-3021-z.'},{id:"B41",body:'Duffau H. The error of Broca: From the traditional localizationist concept to a connectomal anatomy of human brain. J Chem Neuroanat 2018;89:73-81. https://doi.org/10.1016/j.jchemneu.2017.04.003.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"José Luis Navarro-Olvera",address:"luiginavarro97@hotmail.com",affiliation:'
Functional Neurosurgery, Stereotactic and Radiosurgery Department, Mexico General Hospital “Dr. Eduardo Liceaga”, Mexico
Functional Neurosurgery, Stereotactic and Radiosurgery Department, Mexico General Hospital “Dr. Eduardo Liceaga”, Mexico
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After approval, you will proceed in submitting your full-length manuscript. 50-130 pages for compacts, 130-500 for Monographs & Edited Books.Your full-length manuscript must follow IntechOpen's Author Guidelines and comply with our publishing rules. Once the manuscript is submitted, but before it is forwarded for peer review, it will be screened for plagiarism.
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3. PEER REVIEW RESULTS
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External reviewers will evaluate your manuscript and provide you with their feedback. You may be asked to revise your draft, or parts of your draft, provide additional information and make any other necessary changes according to their comments and suggestions.
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4. ACCEPTANCE AND PRICE QUOTE
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If the manuscript is formally accepted after peer review you will receive a formal Notice of Acceptance, and a price quote.
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The Open Access Publishing Fee of your IntechOpen Compacts, Monograph or Edited Book depends on the volume of the publication and includes: project management, editorial and peer review services, technical editing, language copyediting, cover design and book layout, book promotion and ISBN assignment.
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At this step you will also be asked to accept the Copyright Agreement.
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5. LANGUAGE COPYEDITING, TECHNICAL EDITING AND TYPESET PROOF
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Your manuscript will be sent to Straive, a leader in content solution services, for language copyediting. You will then receive a typeset proof formatted in XML and available online in HTML and PDF to proofread and check for completeness. The first typeset proof of your manuscript is usually available 10 days after its original submission.
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After we receive your proof corrections and a final typeset of the manuscript is approved, your manuscript is sent to our in house DTP department for technical formatting and online publication preparation.
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Additionally, you will be asked to provide a profile picture (face or chest-up portrait photograph) and a short summary of the book which is required for the book cover design.
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6. INVOICE PAYMENT
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The invoice is generally paid by the author, the author’s institution or funder. The payment can be made by credit card from your Author Panel (one will be assigned to you at the beginning of the project), or via bank transfer as indicated on the invoice. We currently accept the following payment options:
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7. ONLINE PUBLICATION, PRINT AND DELIVERY OF THE BOOK
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IntechOpen authors can choose whether to publish their book online only or opt for online and print editions. IntechOpen Compacts, Monographs and Edited Books will be published on www.intechopen.com. If ordered, print copies are delivered by DHL within 12 to 15 working days.
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If you feel that IntechOpen Compacts, Monographs or Edited Books are the right publishing format for your work, please fill out the publishing proposal form. For any specific queries related to the publishing process, or IntechOpen Compacts, Monographs & Edited Books in general, please contact us at book.department@intechopen.com
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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. 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In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. 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He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}}]}},subseries:{item:{id:"25",type:"subseries",title:"Evolutionary Computation",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403"},editorialBoard:[{id:"111683",title:"Prof.",name:"Elmer P.",middleName:"P.",surname:"Dadios",slug:"elmer-p.-dadios",fullName:"Elmer P. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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