A selection of different common AI-tools.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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Many researchers were working a lot with development of methods for diagnostics, simulation and adaptation of models. Artificial Neural Networks (ANN) were being implemented in real applications such as e.g. soft sensors to predict NOx concentration in exhaust gas from power plants. Still there was quite some “over-selling” and the enthusiasm for AI in the future was assumed to be useful tomorrow. But it took much longer to get the systems robust enough to be used and fast enough to be applicable in on-line applications. After year 2000, systems started to reach a more mature state and we got IBMs Watson, that could beat the Jeopardy master. Later the Google tool could beat the “Go-master”, a very complex Chinese game. This has changed the perception of AI. It is still similar type of tools as were developed during the 80th, but now they were refined a lot and hardwires has been developed dramatically. This has given us a much more positive perception of what can be done, and a lot is now being implemented. Still there is a risk for over-selling, as the tools are normally not that “intelligent” as we normally think of when we talk about Intelligence. But we are closing the gap day by day.
\nConcerning use of AI in process industry, we cannot just take the tools and hope they will fix everything. It is still important to identify “what is the problem to solve”? With Jeopardy the goal is to be good at Jeopardy, but what is the goal in process industry? It should be to increase production, reduce process variations, implement maintenance on-demand and give operator support. It also means to coordinate and optimize production lines as well as complete plants and later on complete corporations. It also means to adapt to changing customer demands, support in development of new products with production lines as well as handle new business models. These different functions demand quite different tools and thus we will not use only one but several. Often Machine learning is considered being “the tool”, but often there is not data available to implement ML, especially not when starting a new production line. To implement new tools, it is also very important to pre-treat data. You have to sort data in “normal variations” or “anomalies”. You may need to filter data with moving windows, but in different time perspectives. We need to do data reconciliation to handle drifting sensors. And you need to integrate all levels from orders to production planning down to coordinated and optimized production. In this chapter we will discuss a number of different methods as well as discuss integration between the different levels. Over the years many researchers have investigated different AI techniques for different process industrial application. A comprehensive review on different AI models applied in energy systems can be found in [1]. Applications of different AI tools based on simulation models in pulp and paper industry has been presented by researchers including Dahlquist [2, 3, 4, 5]. Applications in power plants have been presented in many articles including Karlsson et al. [6, 7, 8]. In Karlsson et al. [9] a general discussion is made on how to make better use of data including pretreatment of data. Adaptation to degeneration in process models by time is discussed in Karlsson et al. [7]. [10] conducted an extensive review on different AI based soft sensors in process industries.
\nThe mathematicians developing especially ANN have been looking a lot on how the brain works. In \nFigure 1\n we see a principal picture of a human.
\nHow a human handle input from the surrounding.
\nRunning in a forest: The brain stores many different factors locally by “tuning many soft sensors”. During the night strength of connections are enhanced for the most important functions, while other less important connections are eliminated. Some information is used for direct control. Others is stored for use later on.
\nIf it is rainy when you run there is a general feeling that “this was not so nice”. Everything else happening in the forest then will be “colored” by this in your memory, aside of concrete thing like if you meet someone, like a friend, during the run.
\n\nShort term memory: Dorsolateral prefrontal cortex controls information stream from sensors. Skull lobe is for attention. Ventrolateral prefrontal cortex sort information into useful or not useful info. Supplementary motor area (SMA) repeat new memories all over.
\n\nLong term memory: Hippocampus and nearby areas in medial temple globe are essential for long term memory. Facts are stored. Small brain and basial ganglia contain procedural memory, like how to bike or swim.
\nA human may have approximately 120 billion nerve cells. Each connect to hundreds of other cells. Some connections enhance while other decrease signals. Very complex interactions where connections are established and broken continuously. No exact values or memories exist for control, but diffuse input give diffuse output, but with different feed-back mechanisms. The Swedish Nobel Prize winner Arvid Carlsson [11] found out the mechanism of how signals are transferred from the dendrite of one cell to the axon of the next, where complex feed-back mechanisms enhance a connection and thereby also enforced a memory by changing the easiness of transferring new signals. He explored how dopamine works as a signal substance, which we now know is of highest importance in the brain. By back-propagation in ANN we try to simulate this mechanism (\nFigure 2\n).
\nSignals flow in the brain – Many connections and feed-back enhance learning.
Input to the brain is sorted in Amygdala and hippocampus. Signals are sent to different part of the brain Here different signals are enhanced or decreased depending on previous experiences in many different “soft sensors”, built up with tuning of Ca-channels working as parameters in a polynom. “= enhancement factors”. The situation is triggering memory build up. All control is “diffuse” using many different “diffuse” measurements. Different individuals have different sensitivity and number of different sensors like sense for bitterness, sugar, pain etc. Soft sensors get input and react with output to other soft sensors. Signals are sent to direct different biochemical processes like when fear - increase production of Adrenalin and Cortisone. This in turn is affecting many other hormones and proteins etc. Also, microbiome in the stomach and skin send input to the brain on how these organs perform. When you run, the body feel good and e.g. endorphins are produced enhancing performance of stomach, muscles etc. Serotonin levels, gibberellins, insulin, cortisone etc. are interacting and tuning each other, but with influence “from the side” by other sensor inputs. The brain is interacting with all this. This is also the basic concept to mimic in “deep learning”.
\nIf we try to transfer this picture into a control system, it can look like below in \nFigure 3\n.
\nPrincipal diagram of signal processing in a “learning system”.
We start with sorting out “outliers” in pre-processing. This is what the brain does with information from the eye etc. The outliers can be used for anomaly detection. This is principally what is done in Amygdala. We then compare predictions from simulators and soft- sensors to measurements. We trend differences developed by time. Refined data are used for model building and adaptation of models. The models are used for soft sensors, diagnostics, control etc. We also make conclusions in decision a tree from previous experience and identify optimal action to take in different time perspectives. In the brain this is done by utilizing previous experience in a way where we try to “make sense”. This means that we replace missing data with what is reasonable. In our computer system we do this by data- reconciliation using e.g. solving an equation system of physical models to get a best fit. We then take actions by control of many different functions more. In the body, this means e.g. control of sugar content in the blood, release of adrenalin to meet threats or melatonin to make you tired and go to sleep. We learn buy tuning soft sensors and decision trees with the new information just as the brain does, but where the brain is very much more complex than what we can handle today.
\nIndTech’s market, i.e. Products and systems for industrial digitization and automation in the world are worth around USD 340 billion in 2016/2017 and have an average growth rate of 7–8 percent. The area can be divided into two parts: IT (industrial IT) and OT (operational technology). The share that can be categorized into industrial IT is about USD 110–120 billion. The remaining USD 220 billion is operational technology for the factory floors and in the field. It, in turn, is traditionally divided into discrete automation (about 45 percent) and process automation (about 55%). OT includes various types of industrial control systems (ICS) and field equipment such as instrumentation, analysis, drive systems, motors, robots and similar.
\nFor the future of AI, we can see that this comes deeply into all these industrial market segments, but also far beyond as not only for industrial applications. The tools thus will be developed for one application, but then will be used also for other applications most probable.
\nThere are many different methods developed. Some of them are very similar or aim to solve the same type of problems. If we look at Machine learning (ML), we have e.g. Regression. Artificial Neural Networks (ANN), Support Vector Machines (SVM), Principal Component Analysis (PCA), Partial Least Square regression (PLS) and etc. They both aim to sort different variables into group that correlate to different properties or faults.
\nPLS and ANN, both are very useful to create soft sensors. Deep learning is a sophisticated version of the ANN, but with the goal to produce models that can do much more than just be a soft sensor, which predicts one or more qualities. Examples of soft sensors is to predict strength properties of paper from e.g. NIR data and process variable values in paper machines, amount of different kind of plastics in Waste combustion plants or protein content in cereals in agriculture from NIR spectra. The deep learning on the other hand can be used to teach a robot to pick out machine components that are scrapped from a conveyor belt for instance. This then includes image pattern analysis from camera monitoring of the parts passing.
\nA selection of different tools is listed in \nTable 1\n.
\nMachine learning methods principally use a lot of process data measured preferably on-line, and identify correlation models from the data, which can be used for different purposes like soft sensors, anomaly detection and others.
\nThere are several different machine learning methods. Some are correlating a specific property to process data. Reinforcement learning is described in e.g. Gattami Ather [12]. It is used in problems where actions (decisions) have to be made and each action (decision) affects future states of the system. Success is measured by a scalar reward signal and proceed to maximize reward (or minimize cost) where no system model is available. One example of this technique is deep reinforcement learning which was used in AlphaGo that defeated the World Champion in Go. Here a Q function is approximated with a deep neural network. Minimizing the loss function with respect to the neural network weights w is made as given below
\nIf the system is deterministic the model is given by
\nIf the system is stochastic the model is given by
\n\n\n
In Werbos Paul: A Menu of Design for reinforcement learning over time [13] reinforcement methods are described more generally.
\nIt is interesting to create soft sensors by creating models correlating process measurements on-line to quality measurements from samples analyzed at lab. The soft sensor then can be used to predict the quality property on-line from feeding the on-line measurements into the soft sensor model. There are several different methods for the regression, and a number of alternatives are given in \nFigure 4\n below.
\nA number of methods that can be used to develop soft sensor models from process data.
In \nFigure 5\n we see how the data flow can look like for data collection, data pre-processing, model building and model validation. Here NIR measurements are correlated to properties like lignin content.
\nData flow for building and verification of soft sensors.
Soft sensors also can be built with other methods like using ANN, Artificial Neural nets. There are advantages and disadvantages with the different methods, but also commonalities. You need good data for building the models. This means that data need to be spread out in the value space in a good way. If we only have “white noise” the models will be unusable. We need to vary all variables in a systematic way to get useful data for model building.
\nGaussian Process Regression takes more memory but gives better regression models than many other methods like (Nonlinear) System Identification, Neural Networks and Adaptive learning models. Can also be Combine with physics-based models. The method is presented in e.g. Fredrik et al. [14]. In \nFigure 6\n we see a first attempt to predict kappa number of pulps after a digester for two different wood types, hardwood and soft wood. The training data fits quite well, while the predictions are less good. By using more data and fine-tune the estimation of residence time in the reactor the prediction power became significantly better. It went from R2 = 54 to R2 > 90.
\nExample of Gaussian process regression (GPR) for kappa prediction.
Artificial neural nets try to mimic the brain. In a simple way we can use the equation below to show how it is calculated:
\nIn \nFigure 7\n we see three input variables to the left. Each variable is multiplied with a weight factor towards the two summa-nodes, where the products are summarized. Next these values can be treated to pass a threshold or only be passed on and multiplied with a second constant αi. The two products are summarized again, and we get a prediction of the value of a wanted property. When you build the net, you look at the difference between the measured and the predicted value and adjust the weight factors until you get a good fit. When you have been testing one set of input variables you go to the next and proceed for all data you have and try to get a fit that is the best for all input variables together. This is a simple net with only one “hidden layer”, but you can have much more complex versions with many variables and many layers. If you have many layers the problem though can be that you get a good fit for the training data but it may also give risk for “over-fitting”, which means less stable predictions.
\nA simple artificial neural net, ANN.
An example of a first commercial application of ANN was for prediction of NOx in power plants. In \nFigure 8\n below we see a regression for the power boiler number four in Vasteras.
\nA plot showing the correlation between prediction with an ANN and measurements of the actual NOx content in the exhaust gases from a power plant (coal fired boiler 4 at Malarenergi).
PLS is very popular to use for making prediction models after performing factorial designs of experiments. The basic idea is to start with a linear regression for a line, \n
Here A-F are constants you get from fitting the experimental data to the model. If we use factorial design, it means that we try to expand the prediction space as much as possible within given borders. This means that we shall have a good distribution of experimental data in all parts of the space, and not only close to origo or in one part of the space. This means for example that you shall not make correlation for one variable at a time but vary all variables in a systematic way. In Ferreira et al. [15] the Box–Behnken design is described more in detail. In \nTable 2\n below we see an example for three variables:
\n\n\n
| \n
A selection of different common AI-tools.
Experiment no | \n\n\n | \n\n\n | \n\n\n | \n
---|---|---|---|
1 | \n+ | \n+ | \n+ | \n
2 | \n+ | \n+ | \n— | \n
3 | \n+ | \n— | \n+ | \n
4 | \n+ | \n— | \n— | \n
5 | \n— | \n+ | \n+ | \n
6 | \n— | \n+ | \n— | \n
7 | \n— | \n— | \n+ | \n
8 | \n— | \n— | \n— | \n
9 | \n0 | \n0 | \n0 | \n
10 | \n\n\n | \n0 | \n0 | \n
11 | \n0 | \n\n\n | \n0 | \n
12 | \n0 | \n0 | \n0\n | \n
Factorial design of experiments with three important variables to predict a certain qualitative variable like paper property, lignin content, content of different plastics etc.
The first 8 experiments give the linear regression while the last four gives the non-linear components. As we vary all variables independently, we get the interaction between the variables directly. (+) means here a higher amount or concentration of the variable while (−) means a low. (0) is Origo and \n
It is important to have an equal distribution in the whole sample volume of measurements. If a high concentration of samples around origo – the impact of the “real” samples will be too small. It is better to have a few good samples well distributed instead of many around origo or some other part of the space. By varying several variables at simultaneous also catches interactions between the variables. The reason while sometimes models built from only on-line data in a plant may have very little prediction power is if we have a number of important variables with controllers, and only get the white noise due to poor control. By really varying these variables in a systematic way as proposed by factorial design, we can build robust prediction models. If the models still are not that good, it may be because we are not varying or measuring all important variables. Then we should change the variables in the factorial design. If you do not know which variables are the most important you can start with the factorial design scheme in \nTable 2\n but add more variables and just vary them around origo and perhaps some other random point. From this first scan we can decide which variable to focus more experiments on.
\nThe factorial design scheme can also be seen as values at the corners of a cube and where the axis crosses a sphere around the cube as seen in \nFigure 9\n below:
\nFactorial design with values in all corners of the cube and where axis cross a sphere surrounding the cube.
If it is expensive to run all experiments, you can make a reduced factorial design, where you principally pick some of the variants randomly and make a PLS model. You then add one or two experiments and see how much better it becomes and proceed until you feel satisfied. This can be illustrated as in \nFigure 10\n.
\nReduced factorial design.
Principally the regression is made so that you start with a line through all data in the space and calculate the square of the distance between the point and the line. You add all values for all points. Then you change the direction and make a new try. This then proceeds until you have found a line that has least sum of square errors. You then make an axis perpendicular to this first line and proceed to find a plane.
\nOne example can be seen in \nFigure 11\n.
\nThe plane direction is corresponding to the line, the down wards bending the non-linearity and the cross bending of the surface shows interaction between the different variables x1, x2 and x3.
In \nFigure 12\n we see what wavelengths have importance and to what degree for predicting the investigated property. At the top we have regression coefficients for AIL, Acid Insoluble Lignin, and at the bottom for ASL, Acid Soluble Lignin.
\nExample of regression between wave lengths and lignin concentration in wood.
We can see from the regression coefficients in \nFigure 12\n that there is a significant difference between the spectra, indicating that the chemistry differs quite a lot. This as each wavelength corresponds to vibrations of a certain chemical bonding, like C-H, C-H2, C-O, C=O, etc. This example is taken from Skvaril Jan [16].
\nConfounding means that some effects cannot be studied independently of each other. This is very much the case in combustion processes, water treatment, process industries like pulp and paper etc.! This is why the factorial design of experiments make so much sense. In some cases, though there is no interaction between different variables, and then it might be OK to build linear models, but this is often more exceptions than the rule. There are a number of PLS methods. One popular version is PLS Regression which is presented by e.g. Svante et al. [17].
\nIt is interesting to determine both process and sensor faults. This can be performed in many different ways. You can listen to noise from an engine that indicates some fault. Or you measure that the temperature has become too high somewhere. Fault detection can be systemized by using different tools and BN, Bayesian Networks, is a tool suitable for identifying causality relations and probability for different type of faults simultaneously.
\nBayes was a priest in Scotland first discussing correlation versus causality. Correlation means that you can see how different variable are connected to each other, while causality means to take it a step further and also identify true dependence between a variable and a fault or similar. If we see that there is a correlation between homeopathic levels of a substance and effect on health, this can be a correlation but hardly that the homeopathic medicine is causing the good health. A lot of correlations are just random! With the Bayesian net you try to find the causality between different variables and a fault or similar and also quantify this. If we have a lot of experimental data we can use this to tune the BN, but if we do not have it but know from experience that there is a causality, we can make a reasonable guess of the importance in relation to other variables and use this for the BN. This gives an opportunity to make prediction models without “big data” and you can combine this input with real measurements in the plant.
\nApplications of BN for condition monitoring, root cause analysis (RCA) and decision support has been presented in e.g. Weidl G.,Madsen A L, Dahlquist E [18]; [19, 20] and adaptive RCA in Weidl et al. [21]. Weidl and Dahlquist [22] also has given a number of examples of RCA in pulp and paper industry applications like digesters and screens. In Weidl and Dahlquist [23] applications more generally for complex process operations are presented where object-oriented BN are utilized. In Widarsson [24] Bayesian Network for Decision Support on Soot Blowing Superheaters in a Biomass Fuelled Boiler was presented and in.
\nIf we have a number of BN variables U = {Ai} and parent variables pa(Ai) of Ai we can use the chain rule for Bayesian networks to give the probability for all variables Ai as the product of all conditional probability tables (CTP) P(SkIH1,H2,…Hn). Here Sk is the child node which can be observed status, measured values by some meter, a trend or similar) and Hi is the parent node (assumed causes or conditions causing a change in the child node state). The CPT can be trained by real measurements with conditions and related failures or created by using experience by operators or process experts. This is of specific interest when you want to include possible faults occurring very seldom, but severe when actually happening. Data might also be created for training by running a simulator with physical models and with different faults.
\nThe chain rule for all CTPs is as seen in Eq. 7.
\nAn example of a BN for a Root Cause Analysis function for a screen in e.g. pulp and paper industry can be seen in \nFigures 13\n and \n14\n.
\nA Bayesian model for RCA (root cause analysis) of a screen.
A principal drawing of a screen with sensors.
If we have identified that a variable should be within certain limits or we have made a model using SVM or PCA or similar, we can see if the measured set of variables is within the boarders for a class or group. Both these types of measures can be used for anomaly detection. This can be very useful to identify if the process goes out of normal operations even if you have not passed the limits for a single variable.
\nSvante et al. [25] have presented the tool PCA in an article already 1987. PCA is often in the same software package as PLS but has a different use. In the PCA we plot all measured data onto different planes to see how the variables distribute in the plane. From this we can see that variables close to each other are affecting a certain property in the same way, while those on the opposite side of the diagram are having also the opposite effect. If the variables are close to Origo, we can believe they have not much effect at all on the studied property.
\nThe score vector is a column of T. There will be one score vector for each single PC. Each experiment will have one value in the PC1 and one in the PC2. You plot all experiments in a coordinate system with PC1 and PC2. If we plot all experiments in a diagram with PC1 and PC2 we can get as in \nFigure 15\n.
\nScore plot (t). First sample no 1 at t = 0 and following no:s following time steps.
In \nFigure 15\n we have plotted the time series of measurements and can see that there is a development from left to right as time passes by, along PC1. This shows that something is happening by time. We can also make a loading (p) plot. The loading plot shows how much each variable contributes to each PC. Each PC can be seen as the linear combination of the original variables
\nThe loadings are the coefficients pji. Each variable can contribute to more than one PC. If we have more than two PCs, it can contribute to all PCs. In \nFigure 16\n we see the p-plot for a number of variables:
\nP-plot for eight variables in the PC1 – PC2 coordinate system.
From \nFigure 16\n we can see that X3 and X6 have small impact while X4 and X8 have stronger impact but reverse to each other. X1 and X2 are following each other closely.
\nIn \nFigure 17\n it can be seen that when the set of variables is within the circle the process is running OK, but when going outside you should take a look and try to get it inside the circle again. This is a bit towards diffuse control, like in the human body.
\nUsing the plot to control the process by keeping within a certain area of the PC1-PC2 space.
You can use the p-plot also to classify a number of faults. In \nFigure 18\n we see an example where vibrations, temperatures and electric power consumption was used to predict different type of faults. The faults were implemented at the lab and the variables measured. From this we could see that the variables were forming different patterns.
\nUse of plots to classify different faults.
The PLS is principally partial least squares or projection to latent structures. Principally you do an interactive PCA for both X and Y matrices.
\nThis can schematically be seen in \nFigure 19\n below.
\nThe principles for PLS (partial least square) regression.
Layout of a complete system where different level and functions are connected and integrated.
U gives starting values for T, and T back to U iteratively. Interdependency. When the difference between two iterations is below a certain value, we take this as the result.
\nThere are a number of versions of this. PLS2 general = all Y; PLS1 for each single Y; PCR also for each single Y, and no interactivity between Y and X (first X, then Y); PCR is often used by statisticians while PLS by application engineers normally.
\nThe result from the PLS regression will be a ploynom. If only linear: \n
In SVM we try to find the balancing point for different clusters and then try to distribute the different measured values as close as possible to one of these cluster balancing points. This is giving a similar type of clustering but is usually used for a big set of data where you want to find out how many clusters there might be. You can systematically test to have more or less clusters and see how the data fits from a statistical perspective into more or less clusters.
\nIn Narend S. Kumpati [26] Adaptive control using neural networks is presented. Since then MPC, both “fixed” and adaptive, have come to use in many applications in process industry. There is even a Journal of Adaptive Control and Signal Processing. In a recent number, April 2020, Merve et al. [27] discuss Improving transient performance of discrete-time model reference adaptive control architectures. This area is binding AI, modeling and control together.
\nIn \nFigure 20\n the structure implemented in the FUDIPO project (
In the second structure we have primarily open source programs like Red Node for configuration of the complete system, linking everything together. MatLab is replaced by Python and Simulink with OpenModelica, Dymola and these are then complemented by other simpler software for different functions. The idea is that you can test all functionalities together in the open source environment. If you have a smaller system you can configure and use this also for “the real case”. If you have a bigger system demand you probably go for commercial software to also get support for the functions, and perhaps also make a service contract with someone who can support sustaining the system, and upgrading on a frequent basis, as the production plant is developing.
\nFrom this overview we can see that there are many possibilities with use of AI-tools, but it also takes some effort to understand which tools are useful to solve specific problems.
The solutions must be robust. 100% of operational space must be covered in a reasonable way.
Diagnostics must detect real faults, but avoid detect “false faults”
\nAutonomous systems may be good, but you have to identify the boarders and limits and what are important functions to work with.
Need to define the problem to solve!
Optimization and adaptive systems and functions should include all important functions. To do so you also need to vary the important variables. You cannot train a system on constant values! Factorial design of “experiments” is then important.
Many new tools are being accessible, but you need to understand how they work! Do not guess.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 723523.
\n\n
Some basic concepts are necessary to define as Fluorescence, which is a form of luminescence, that is, it is a process of light emission, caused by an energy, in this case it is by ultraviolet rays and that said energy is absorbed in form of electromagnetic radiation to later be emitted in the form of wavelengths and thus can be captured by an image system.
And what is the Indocyanine green? (ICG). As it is a colorant that is soluble in water and has a spectral absorption of light of approximately 800 nanometers, this spectrum is capable of binding both oxygenated and reduced hemoglobin and has 5 pharmacological characteristics: one that is not metabolized by therefore it is considered almost inert by binding to plasma proteins. Two, which is eliminated by a concentration gradient, that is, passively. Three, it is eliminated by the hepatocyte into the bile canaliculi. Four, it does not suffer from enterohepatic circulation and fifth, that its use is clearly diagnostic and not curative since its approval by the FDA in 1960 when Fox IJ of Mayo Clinic [1], showed in a work the physical and metabolic properties of this substance and its use diagnosis in liver diseases, ophthalmological, cardiac, neurological, etc.
Colorectal Cancer is the 4th most frequent in the USA, more than 135,000 new cases are diagnosed per year, of which 95,500 are colon and almost 40,000 rectal, with an estimated and unfortunate mortality of more than 50,000 cases, that is, approximately 35% [2] . In Spain, despite the fact that a little more than 41,000 cases per year of colorectal cancer are diagnosed according to the Spanish society of medical oncology (SEOM), it constitutes the first cancer in incidence in that country, logically due to the demographic density - incidence relationship and with a mortality close to 25% [3].
Another concept we must handle is anastomotic leakage because as we all know the standard care in colon and rectal cancer to date is surgery, before or after neoadjuvant treatment. And what is an anastomotic leak?. Since a very simple concept is the one proposed in 1991 by the study group of surgical infections in the United Kingdom [4], where it comments that “it is the escape of luminal content from the surgical union between two hollow viscera”. Concept that seems very simple, but that generates a lot of controversy at least in the literature where they talk about the subject, because these works are not homogeneous many times at least in the diagnosis of this entity since there may be an anastomotic leak, for example radiological, It is that detected in imaging studies performed routinely, without the patient showing signs or clinical symptoms, but does not require changes in management. To give an example, it is the typical case of the patient who has been left with an ileostomy or protective colostomy and before closing or restoring it, imaging studies are performed and a leak is detected or the patient who is performed due to postoperative leak prevention protocols blood markers such as C-reactive protein, procalcitonin or other acute phase reactants that, despite the patient being asymptomatic, can lead to imaging studies. It can also be an anastomotic leak with a minor clinic where the patient presents intestinal or purulent discharge from the wound or drainage, associated with fever, leukocytes, presence of abscess. And they do not require surgical intervention at least initially, but lengthens the hospital stay, the use of antibiotics, the need for percutaneous drainage, endoscopic procedures, etc. And the anastomotic leak that already presents with greater symptoms, that is, with more spectacular symptoms due to a degree of severe disruption of the anastomosis and that does require surgical intervention.
And how frequent is an anastomotic leak in colorectal surgery? This will depend on the anastomosed segment. And according to this multicenter and prospective study carried out in Europe [5], the leak rate of an ileocolic anastomosis varies between 1 to 18%, of the colo-colonic between 2 to 13%, ileo-rectal between 3 to 11% and colorectal or coloanal between 5 to 21%, although on average the Spanish Rectal Cancer Project carried out in the main colorectal surgery units in Europe showed an average leakage rate for rectal anastomosis of 10% [6]. And well, the anastomotic leak is associated with a large increase in morbidity and mortality, therefore it is the most feared complication by every surgeon and any health system in the world due to expenses that generates that are calculated that they are approximately between 1.6 to 5 million Euros per year or 40,000 € approximately per patient [7].
And what are the risk factors for an anastomotic leak to occur? They are preoperative risk factors that generally depend on the patient and that are many but the most important seem to be obesity, age, sex, tobacco, alcohol, steroids, non-steroidal anti-inflammatory drugs, nutritional status, type of ASA, tumor size, the performance of chemo or radiotherapy previously and intraoperative factors that depend a lot on the surgeon and that perhaps are the ones that we can intervene or modify with some exceptions such as the distance from the anal margin, since the closer the greater the risk, but if we could modify, for example, the duration of the intervention, perioperative sepsis or need for transfusion, the performance of protective stomas that are known not to reduce the incidence of anastomotic leaks, but if the severity of their presence, the intestinal preparation that some studies say that there are no differences with their use, but others who speak that if especially when using them with antibiotics and especially orally, this for a reason perhaps from the gut microbiota. And another very important factor is the quality of the anastomosis that we perform, because as we all know it must be tension-free and adequately vascularized, regardless of whether it is handsewn or mechanical. In addition to predicting the risk of anastomotic leak, there are many scales in the literature, some that predict morbidity and mortality and indirectly the risk of leak, such as the ASA, APACHE, POSSUM and others more specific such as the Dekker Score or Colorectal Leak Score (CLS) [8], which is perhaps the most used that it consists of 11 items that score the patient between 0 and 41, with a high risk of AL being a score greater than 11; this with a sensitivity of 67% and Specificity of 89%; However, on the internet, very practical and easy scales and calculators are available, such as the
Now, how do we evaluate intraoperatively that our anastomosis is fine and that it will not leak? Well, there is a subjective assessment such as the visualization of the anastomosis, with the fingers we evaluate the caliber, the color of the serosa and the mucosa, which bleeds when cutting the intestine, palpating the pulses of the Riolano arch, etc. But unfortunately demonstrated by many works and corroborated by Karliczek in 2009 [11], the prediction of AL with these methods is very low and he recommends in his work to carry out some other tests to make a more objective assessment and here they enter by for example, the verification of donuts when we use mechanical suture, air leak test or with methylene blue as sometimes used by some bariatric surgeons and or the performance of intraoperative endoscopy. Regarding air leakage, in a systematic review and meta-analysis published in 2016 by a Chinese group [12], they showed that ALs are lower in patients who undergo the test vs. those who do not, but that it is not statistically significant and that when the air test is positive that this occurred according to the review of the multiple works on the subject between 1.5 to 24.7%, the AL is higher 11.4% vs. 4.2% in those that is negative. And this is the reason why it continues to be used because in the cases that are positive, some measure must be taken, be it reinforcement of the anastomosis, performance of protective ostomies or replacement thereof.
The performance of intraoperative endoscopy, this allows us to evaluate the air leak, the staple line, presence of bleeding or areas of ischemia. In fact, there is a classification in degrees proposed by Alessio Pigazzi et al. [13] of the University of Irving, California. Grade I is an anastomosis with the pink mucosa, well perfused through the entire staple line. Grade II there is ischemia or congestion in less than 30% on one side of the anastomosis and Grade III there is ischemia or congestion in more than 30% on one side of the anastomosis or any degree on both sides. In this work with 110 patients with rectal anastomosis who underwent endoscopic evaluation, 96 being Grade I, that is, normal, 10 were Grade II and 4 patients were Grade IIII. Of these 4, all were taken to Grade I, that is, the anastomosis was redone. And the percentage of leakage was 9.78% for the normal ones, that is grade I, that is 9 patients out of 96. Of 40% in Grade II, that is 4 patients out of 10 and 0% in grades III that they took to GI. What this study showed despite being with few patients is that Grade III patients have to have the anastomosis re-done, Grade II have a very high risk of AL, so some other measure would have to be taken and Grade I despite being normal they escape up to almost 10%; therefore, is it possible to have another method that reduces this risk of AL?
And the answer seems to be yes, and already in 2010, 50 years after the FDA approval of Indocyanine Green, a German group made the first publication on the use of green to prevent anastomotic leaks in colorectal surgery. In this work they included 402 patients divided into two groups. A group who underwent perfusion of the anastomosis with green between 2005 and 2008 and whose leak rate was 3.5% and a retrospective group between 1998 and 2003 who did not evaluate perfusion with green and whose rate of AL was 7.5%, that is, 4% more than the group with green. This work carried out by the disciples of Dr. Christian Tons was a dedication for him who died in 2008 before its publication, this because he is considered the pioneer of the use of this technology in colorectal surgery and inventor of the first system for this, the IC View® from Pulsion Medical Systems [14].
In these almost 10 years, interesting scientific publications on the subject have begun to appear and also private companies have improved the technology, for example a Canadian commercial company called Novadaq® appears, which is leading, already financed and supported several works in this regard with its system called PINPOINT ™ for laparoscopic surgery or the SPY Elite ™ for open surgery [15]. In fact, this company began to be part of Stryker in 2017. And thus also intuitive since 2016 its latest generation Da Vinci Robot Xi, the Firefly system™ for fluorescence use [16]. Companies like Medtronic®, Storz® among others have also entered the market with this technology.
The first prospective, multicenter study with the use of ICG in prospective colorectal surgery was called Pillar II published in 2015 [17]. Here the utility and feasibility of the use of indocyanine green in left colectomy and anterior laparoscopic rectal resections were evaluated using the PINPOINT™ technology from Novadaq®. Among 11 hospitals in the USA, 139 patients were included, 44% operated for diverticulitis, 25% for rectal cancer and 21% for colon cancer. The feasibility of using green was 99% with 1.4% AL and the interesting thing about the work is that the use of this technology allowed 11 patients, that is, 8% to change the area where the colon was cut due to poor perfusion in the site previously chosen by the surgeon before the placement of green, and specify that of these 11 patients when doing this, none had AL.
In 2017, the first systematic summary and metanalysis with what was published up to that date on the use of green to prevent AL in colorectal surgery was published by Espin et al. [18] in this publication after the exclusion of many methodologically weak studies, they include 5 non-randomized studies with 1302 patients of which 555 were operated using ICG and 747 without ICG. The overall rate of AL in this review was 7.4%, demonstrating that ICG reduces the risk of AL in colorectal cancer with a p = 0.06. And specifically, it was seen that in rectal cancer the leak rate in the group with ICG was 1.1% vs. 6.1% in the group without ICG. This with a p = 0.02. But it also shows that when analyzing the use of green in both malignant and benign diseases, there are no significant differences in the prevention of leakage with its use. The authors in this review conclude that the literature up to that point is very heterogeneous and that new randomized, randomized and multicenter studies should be carried out for what they propose the ICEBerg Trial [19], a study carried out to evaluate the use of ICG vs. not in colorectal surgery.
Morales Conde et al. published in 2019 a prospective, monocentric study [20], that included 192 patients who were divided into 4 groups. Group A consisted of 67 patients undergoing right hemicolectomy, group B 9 patients undergoing segmental resection of the splenic angle, Group C with 81 patients undergoing left hemicolectomy, and group D with 35 patients undergoing anterior rectal resection. There was a change in the area of colon section in 35 patients, that is, 18.2%, and these were distributed in 4 (6%) of Group A of right hemicolectomy 1 (11%) of group B of segmental resection of the splenic angle, 21 (25.9%) from group C for left hemicolectomy and 9 (25.7%) from group D for anterior resection. The leak rate was 2.6% (5 patients), but none of the AL have been those that were able to change the cut site with the evaluation of the ICG.
In January 2019, another systematic review and meta-analysis on anastomotic tests in colorectal surgery in the new millennium was published that included a total of 11 articles with 3844 patients and where direct analyzes were compared between the control group, that is, the one that was not did no intraoperative leak test (No IOLT) with which it was verified with ICG or with ALT (Air Leak Test) and with IOC (Intraoperative Colonoscopy). This meta-analysis concluded that AL are higher in the No IOLT group, that is, no test compared to green with a p = 0.0004 and also that they are higher when compared with ALT (Air Leak Test) and IOC (Intraoperative Colonoscopy), but these data were not statistically significant [21]. In September Wexner et al. [22] recommend the quadruple evaluation of colorectal anastomoses to achieve the greatest possible safety, doing it in the following way: First ICG to decide the level of the proximal colon cut, second air test to the rectal stump, that is, before doing the anastomosis, third confirmation of the donuts from the self-suturing machine when performing the anastomosis and fourth the intraoperative colonoscopy with white light and again with green to evaluate the perfusion of the mucosa. In this reading it is recommended that what should never be lacking is the green test, but that one test does not discriminate against another.
In 2020 the FLAG randomized trial [23], with 377 cases, 187 had ICG and 190 were in the non-ICG group and they demonstrated ICG did not decrease the rate of AL of high anastomoses (9–15 cm from the anal verge), at 1.3% vs. 4.6% in the non-ICG group (P = 0.37). In contrast, a decrease in AL rate was found for low (4–8 cm) colorectal anastomoses (14.4% in ICG vs. 25.7% in the non-ICG group; P = 0.04).
Currently, some large randomized studies are being carried out such as the PILLAR III [24] and two more which are in the recruitment phase [25, 26], that is expected to have soon any results about this. And on the other hand, they are trying to investigate and elucidate a question that many colorectal surgeons ask themselves. How green should green be? so that we can say that the evaluated tissue is well perfused. And this question is the one that many of the detractors of this technique ask themselves that perhaps creates uncertainty when they face a real-time image with green. And for this the experts in conjunction with the companies are trying to find a solution and for that at least Medtronic® with its new technology called Elevisión® [27], have included a system for quantifying green in percentages, where through colors and on a percentage scale that it goes from 0 to 250% we can quantitatively know the irrigation of each area of the colon (Figure 1). And this has already been working and published by plastic surgeons. They have shown when performing a skin flap, that when an area of the flap has more than 33% of the most perfused point, it can be ensured that 88% of cases that area will not be necrotic. And when that value is less than 25% in 90% of the cases it will be necrotic [28, 29]. This is being tried to evaluate and agree, that is, what percentage of perfusion we should have in the colon to decide that it is well vascularized.
Quantification of the vascularization of the colon.
Now indocyanine green only serves to assess anastomotic perfusion? And well, although perhaps if it is its most important function, it may have others like the ones we show in a video published by Vargas et al. [30], in the Spanish journal of surgery of a clinical case of upper rectum cancer where we use green not only for the evaluation of the anastomotic perfusion but also for marking the tumor and as a guide at the time of lymphadenectomy, these very important points to achieve an ideal oncological or radical surgery. The important difference with the little-published marking is that we have done the marking by rectoscopy 4 hours before surgery (Figure 2), diluting the green ampoule in 100 cc of serum and from there we have injected 0.3 cc to 2 cm at the submucosal level distal to the tumor in order to locate the lesion intraoperatively because it is very small (only 3 cm) and to mark the lymph nodes to be resected as a kind of sentinel lymph node (Figure 3). What is published in the literature in this regard are still clinical cases or videos, but there is some experience in the literature regarding lymphadenectomy, especially in right colon tumors with the intention of performing surgery with D3 lymphadenectomy or complete excision of the mesocolon as shown by the work on a clinical case of Complete excision of the mesocolon in a right hemicolectomy using the Firefly fluorescence system of the Da Vinci® robot [31]. Now the injection of green in published cases is performed intraoperative technique of subserosal ICG injection with a fine needle for sentinel lymph node (SLN) [16]. This technique is feasible in very large tumors that can be located without problems via laparoscopy or robotics or that have been previously marked in a conventional way with ink (an important difference with our technique). The studies published to date do not show any statistically significant difference in the number of lymph nodes dissected using marked-oriented lymphadenectomy in advanced tumors but in early colon tumors, that is, T1 or T2. These findings have been demonstrated by Asian groups that have the most experience in this, as shown in a work published in 2015 but using conventional ink marking [32] and this other by, which is the only one published to date, used indocyanine green as a marker of the tumor [33]. In middle-low rectal cancer local recurrence greatly affects the treatment efficiency and the survival outcomes for patients with rectal cancer. Lateral pelvic lymph node (LPLN) metastasis (LPNM) is an important factor for local recurrence after surgery in patients with middle-low rectal cancer, and approximately 8.6% to 21.0% of patients with rectal cancer have associated LPNM. As one of the effective treatment methods, laparoscopic LPLN dissection (LPND) can significantly reduce the local recurrence rate compared with simple total mesorectal excision (TME) surgery. In clinical applications, LPND is limited by various complications because the ureters and hypogastric nerves might be damaged without efficient guidance, and for this using ICG improve the dissection increasing the numbers of lymph nodes harvested and decreasing complications [34].
Location of the tumor marked prior to surgery with ICG.
Lymph node marking with ICG for lymphadenectomy.
There are also publications of its use in various situations, such as in the Japanese article of August 2019 by et al. [35] where this group devised a Kit that they called IRIS U Kit that allows them to transilluminate the urethra and prostate in transanal total mesorectal excision (TaTME) with the intention of avoiding one of the most feared complications of this technique, which is the injury of the urinary tract. As well as this, there are already published cases of its use, for example, in the transillumination of the ureters in very difficult cases from the surgical point of view, such as big tumors, complicated diverticulitis or pelvic surgery [36]. In 2017, a Belgian Group published a systematic review [37] of the use of green as a guide in the diagnosis and surgical treatment of hepatic or peritoneal metastases of colorectal origin. This work concluded that the use of green facilitates the detection and resection of hepatic and peritoneal metastases of colorectal origin.
Anastomotic leaks after colorectal surgery continue to be a serious public health problem; therefore the use of new therapies could minimize this problem.
With regard to standard tests for the prevention of ALs, they continue to be used for the structural evaluation of the anastomosis, but with the knowledge that their efficacy is often insufficient; for this reason the use of fluorescence allows us to evaluate anastomotic perfusion is becoming more and more important every day and gives us greater surgical safety for the benefit of the patient.
In addition, we must remember that the ICG is not only limited to the anastomotic perfusion, new functions begin to emerge, such as its use in tumor marking, lymphadenectomy, location of ureters, urethra, liver and peritoneal metastases, among other functions.
The authors declare no conflict of interest.
Anastomotic leaks Indocyanine green Spanish Society of Medical Oncology Food Drug Administration American Society of Anesthesiology Colorectal Leak Score Air Leak Test No intraoperative leak test Intraoperative Colonoscopy sentinel lymph node Lateral pelvic lymph node Lateral pelvic lymph node metastasis Laparoscopic lymph node dissection Total mesorectal excision Transanal total mesorectal excision
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