• DDPS Talk date: January 19, 2024
• Speaker: Jan Christoph (UC San Francisco, https://cardiacvision.ucsf.edu/people-jan-christoph)
• Description: Heart rhythm disorders, such as atrial or ventricular fibrillation, are caused by abnormal electrophysiological wave activity which propagates through the heart muscle and induces irregular contractions. Heart cells are electrically excitable, and they contract upon excitation. They can be described as nonlinear oscillators and the wave activity correspond to nonlinear waves of electrical excitation, which can produce complicated spatio-temporal patterns known to emerge in reaction-diffusion systems. Presently, this abnormal wave activity is still incompletely understood, as it lacks imaging technology that can penetrate the heart muscle tissue and resolve the three-dimensional electrophysiological dynamics within the heart walls. Consequently, diagnostics are limited, and it remains challenging to develop better therapies. In this talk, I will discuss how artificial intelligence (AI) can be used in combination with high-speed fluorescence and ultrasound imaging to overcome these limitations. I will show how it is possible to compute or predict the heart’s electrical dynamics from its mechanical deformation, and I will demonstrate how we train AI ex vivo with isolated hearts in order to be able to make the predictions.
• Bio: Jan Christoph is an assistant professor at Cardiology and Bioengineering in University of California, San Francisco. He also serves as head of Cardiac Vision Laboratory. Jan obtained PhD in Biophysics at University of Gottingen, Germany in 2014. He did his a postdoctoral study at Max Planck Institute for Dynamics and Self-Organization from 2014 to 2018 and served as a staff scientist at Department of Cardiology in University Medical Center Gottingen, Germany before he come to UCSF. He has earned NIH New Investigator Award DP2 in 2022.

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All right. Welcome everyone to the DDPS seminar.  Before we introduce our invited speaker,   let’s go over some rules and logistics.  First, please mute yourself during the   talk. But if you have questions, you’re  welcome to unmute and ask questions. Or  

You’d have to post your questions so that we can  address them in q&a session at the end. Second,   today’s GDPR seminar is open to external audience.  Therefore, no classified discussion is allowed.   Finally, the talk today will be recorded  and uploaded in our YouTube channel. Okay,  

Let me briefly introduce our speaker today.  It is an honor to host Yan Christopher,   who is an assistant professor at cardio cardiology  and bioengineering in University of California,   San Francisco, please close by from Livermore  where I am. He also serves as head of cardiac  

Vision laboratory in UCSF, and then obtained a  PhD in biophysics at University of Goettingen.   In Germany in 2014. He did his a postdoctoral  study at Max Planck Institute for Dynamics   and self organizations from 2014 to 2018, and  served as a staff scientist at Department of  

Cardio Cardiology in University of Medical Center  going on in Germany, or before he comes to came   to UCSF. He has on NIH new investigator  awards and TP two in 2022. Okay, today,   Yan will talk about predicting heart rhythm  disorders from spatial temporal imaging data  

Using artificial intelligence. Please  enjoy and expect a wonderful talk. Now,   let me ask a couple of questions. If you don’t  mind me, and just to get to know you better and   then make this seminar somewhat informal for first  question is, obviously you are passionate about  

Hurt or medical field in general, is is there any  moment in your life when you realize that? Wow,   this is it? This is the field I would like to  commit my career to do you have that money? So the question was, when  was that moment when I want

It? Yeah, yeah. Yeah. And if  you can describe that moment? Yeah. Yeah, I think, um, one thing that I need to  say and before is that I never wanted to become a   scientist, it was not not a lifelong dream of  mine. When I was younger, I never imagined to  

Be a professor or scientists later on in my  life. I think I did a PhD out of curiosity,   because I wanted to spend time on on working  on quantitative biology, I think there was   my interest somehow. And then spending six  or seven years, almost eight years on this  

One important publication that defined my career  that came out in 2018. In nature, even opened up,   I think the way for me to even consider becoming  a professor. So it was a pretty late decision. So   I was already way into my postdoc and published  an impactful paper and then realized, oh, wow,  

I can actually do this. If I want to, I can, I can  try and get a tenure track faculty position and,   and keep doing this for the rest of my life.  Maybe even. And I think before that, I didn’t have  

Necessarily the plan to do that. I see. It was  a thing. At that point, I was definitely hooked.   I was really intrigued by this type of research  that has had built up over the years. And then,  

You know, in that moment, it became clear. Okay,  I want to do that. That was roughly in 2018. Wow. Well, I didn’t know at some  point in your presentation today.   Maybe you can share. What was that? Paper? Yeah, I will have one slide about that  paper. And it’s awesome. It is  

Kind of the foundation for for the last,  the second half of my talk. This paper I see as well. Okay, the I have one more  question. If you don’t mind. Obviously,   you’re using artificial intelligence  for your research. When were you first   exposed to artificial intelligence and  decided to use that in your research?

So I think the first time I heard about  Convolutional Neural Networks was in the   cafeteria at Max Planck in 2012. And 13 You know,  when Alex net and all that came out and people   talked about it, but for many more years, I didn’t  get my fingers on it. Yeah. It was actually only  

During the pandemic, when our Institute’s shut  down, when I sat at home. And my student and I,   we both kept talking about how we wanted to  progress and make it or not improve certain   computational methods that we have developed  and talked about auto encoders in unit. And,  

You know, I just tried it out and it  worked right away. And it was amazing.   And I will have in my talk, I will have  a few slides about exactly that. Awesome. Awesome. Thank you. Thank you,  and I’ll state is yours. Okay,

Thank you, Sue, for the invitation and the  introduction. Again, my name is John Kristof.   I work at the Cardiovascular Research Institute.  I’m appointed in the Division of Cardiology here   at UCSF. My background is in physics, I obtained  a PhD in physics. And let me briefly introduce my  

Lab. And you will notice here that most people  in my lab also have a quantitative background,   either computer science, physics, or electrical  engineering. And the pictures here are kind of   weighted by how many contributions are how  important these lab members are, or were  

Over the past years. And you can notice here young  labor is a central figure in my lab. He was also a   PhD student and getting an A in Germany and came  down with me to set up the lab here at UCSF. And  

A lot of the work that I will talk about today  was actually done by him. Then we were also able   to recruit Trey last year, who has a background in  physics and computer science worked as a software   engineer and he is interested in computer vision.  So he has built important numerical methods for  

Us. And then on the right side, Daniel, he is  now at Caltech, he was an undergraduate student   who made very important work last year together  with Yun, and on the bottom left here tarnish   who has an interest in you know, everything deep  learning and in particular diffusion modeling and  

He he did the diffusion modeling work that I will  also show so, what what can we do as physicists,   mathematicians, or engineers in cardiology, and if  you are interested in this topic a bit further, I   can recommend this podcast that came out recently  in quantum magazine that’s that’s a really nice  

Magazine I I often read, and Steven Strogatz,  who’s an applied mathematician from Cornell,   he interviewed Flavio Fenn was a colleague of mine  from Georgia Tech, and he spent many years leads   a group there, and they research questions such  as How can we predict what the heart does next?  

And how can we intervene and apply defibrillation  pulses in order to stop heart rhythm disorders,   and they talk about that at length. And we do very  similar research with a slightly different focus,   we try to focus on imaging itself. And we  try to understand the interplay between  

Mechanics and electrophysiology in the heart.  So communities is small, but very persistent   and very active. And very interdisciplinary. We  have, you know, cardiologists, with an interest   in machine learning, we also have a background  in engineering. We have mathematicians, fight   mathematicians, engineers, physicists, and they  all have their different views and approaches.  

But we together we meet quite frequently, at least  once a year, this was, for instance, a meeting in   2018, which also I think helped me to make this  decision that I want to stay in academia and that  

I want to give it a try to keep pursuing these  these projects. And this this research topics that   I’m currently working on. It was at the PRDP at  Santa Barbara. And I would say that these people   like us who have a quantitative background,  are very small group in this huge arena of  

Cardiologist and biologists and physiologists  who research heart rhythm disorders or heart   disease in general. And there’s roughly an even  distribution between you know, mathematicians,   physicists, engineering computer scientists  how to how to say who dominates this field,   say, last year, we organized a meeting or mini  symposium at Siam conference, and this year again,  

We will meet at the same conference. And this  is also something that we we often participate   in or organize. And the people who come there  are regular people who who’ve done have come to   these meetings since many, many years they keep  showing up. So the heart is an electromechanical  

Pump. That is something that I need to introduce  first, the most important property of cardiac   muscle cells and you see here one on the left  side is that they are electrically excitable   they are the transmembrane potential undergo was  variations over time that serves that that’s a  

Way of communicating for these cells. And these  changes are referred to as action potentials.   You see there on the right side, three curves. The  first one, the green one is the action potential.   As soon as cardiomyocyte experiences such an  action potential, it opens intracellular storage  

For calcium and the calcium is then released  into the cell and the calcium kind of fuels   the contraction of the cell. So the contraction  follows the action potentials is elicited by the   action potential. Then, this electric excitation  overall on the global scale, the heart triggers  

And orchestrates the heartbeat, we have in  our heart, multiple centers, the sinoatrial   node and backup node. And in there are cells that  beat autonomously, roughly one time per second,   and then they shoot out electrical excitation  through a cable, and then through through a branch  

Of other cables into the main heart muscle tissue  that is shown here. And this heart muscle tissue   consists of roughly 5 billion cardiomyocytes. And  once this electrical excitation reaches the end   of these so called purkinje fibers, they exit  at these sites excite the first cardiomyocyte  

Or small group of cardiomyocytes, and they pass  on this excitation to the neighboring cells. And   so via diffusive process, this excitation then is  propagated through the entire cardiac muscle and   this excitation propagates through the muscle  tissue at a speed of one meter per second. So  

It’s relatively fast. Then atrial fibrillation  and ventricular fibrillation are the two most   severe forms of heart rhythm disorders. There are  many different flavors of heart rhythm disorders,   but those are the most prominent ones, because  they either affect many, many people or they are  

Highly deadly, so atrial fibrillation affects the  pre chambers of the heart, the atria, that can be   a chronic condition that you can have for many  weeks or months before you have your elective   procedure to get rid of atrial fibrillation. And  the atrial fibrillation itself is very problematic  

Because it can cause heart failure or induced  ventricular fibrillation, which then affects the   main chambers and is immediately life threatening,  however, then trigger fibrillation can also occur   on its own. Without atrial fibrillation, it  can occur spontaneously. And you often have,  

Sadly, these reports here that you can do, I  can update the slide every three, four months,   another celebrity dies from sudden cardiac  death, it is very common, and it affects really,   people at all ages, can sometimes affect people  who do sports, especially in professional sports.  

At a very young age, it can affect people with  genetic defects at a young age. But, of course,   it becomes more and more prevalent, the older  you become. Physicists describe these electrical   wave phenomena with partial differential  equations. And we’ll have a few slides about  

That. And here are some reviews about that and  which nicely summarize the work that has been   done in our field. In short, you can see here an  electrocardiogram at the top and that describes   a sudden onset of ventricular fibrillation, so  the most severe, most deadly form of heart rhythm  

Disorder. On the left side, you can see the QRS  complex here, which corresponds to a heartbeat,   the C corresponds to the atria contracting  this to the ventricles contracting and GC are   three heartbeats. Before all of a sudden, out of  nowhere, this ventricular fibrillation sets on.  

And we associate with this episode here three  computer simulations that describe the spatial   temporal dynamics of the electrical waves that  determine the heartbeat doing these three stages   here. So the normal heart rhythm is caused by a  plane wave that really originates down there with  

The Purkinje fibers inject the excitation into the  heart muscle, then this wave propagates upwards,   and needs to be re initiated by the sinus node.  And here are what happens here is that this wave   becomes perturbed and undergoes a transition into  this spiraling or rotating state and we refer to  

This wave of form here as a square wave scroll  because it’s it’s curled up like that. And this   square wave can even further degenerate into  spatial temporal chaos, which is only on the   right side. And these computer simulations  are supposed to illustrate what we think  

Happens inside of the heart. muscle during these  different stages, we can model cardiac cells in   that sense as relaxation oscillators or nonlinear  oscillators. And you see here an example of a   quite old mathematical model for such a relaxation  oscillator that Fitzhugh Nagumo model and in in  

Such a model you have two equations one stands  for the excitation one for the refractoriness   and the kind of compete with each other whenever  the excitation goes up the refer to nets also go excitation and in phase space you then have  this behavior here that most of the time the  

Cell is in the fixed point, but if you perturb it  slightly if the cell receives excitation from one   of the neighboring cells, then you perturb this  oscillator here over this separatrix and you see   an excursion through face space, which corresponds  over time to an action potential is a mathematical  

Modeling of of the electrical activity can in  principle be divided in either this synthetic   bottom up approach, where you measure all  ions in cells or ion channels and in their   contribution to these transplant their potential  and an ion fluxes to the cells on analytical top  

Down or phenomenological approach such as the  Fitzhugh Nagumo approach, where you kind of   mimic the behavior of action potentials using  these relaxation oscillators. And of course,   over the years, this was back then in the 50s.  Many many different models were developed and we  

Kind of distinguish them into either these ionic,  very detailed models, which are computationally   expensive, or phenomenological models,  which are cheap and, and easy to implement,   but also are less realistic, or any hybrid  version between these two extreme forms.  

And this is kind of the sweet spot. For instance,  defendant comma model is one model is used widely   and there are many other models which are, which  consists of fewer equations and fewer parameters,   but sufficiently many parameters so that you  can recapitulate the most important dynamics  

Of the heart. So, if you didn’t connect all  these oscillators in a tissue, you have them   nonlinear waves of electrical excitation,  which propagates through the tissue and here,   this is a cellular automaton. And you see if,  if you excite one cell passes on the excitation  

To neighboring cells, and eventually, this wave  dies out at the boundary, because it’s followed   by this refractory wave that prevents further re  excitation of the tissue. And this is important,   this is the most important property of our heart  that the excitation is supposed to occur once a  

Second and that it’s also supposed to die out so  that the heart can relax again. The big analogy is   for instance, fire front you have excitable tissue  that is maybe dry grass on the excitation wave  

Itself is a fire front and the refractory powders  the fuel has has burned and has gone into the fire   can turn around and re excite or re ignite the  forest. Now, in a continuous medium, we can nicely  

Simulate this with a PDE s. And in this case, this  is a special form of a reaction diffusion system   you can see here again, this is a diffusive term,  these are local reaction, local reaction terms   that describe the excitability of the tissue. So  again, you have a state and a threshold. And once  

You perturb this oscillator over the threshold,  you have this excursion the action potential and   then due to the diffusion, you have here this wave  that propagates outwards and then dies out at the   system boundaries. Now cardiologists they try to  measure these wave phenomena in patients, however,  

There are many limitations in terms of how  practical it is to access the tissue to measure   and obtain recordings from from patients. The gold  standard currently is to use on so called catheter   mapping. So catheters are inserted into a patient  this procedure is called minimally invasive,  

But nevertheless it is invasive. And then under  anesthesia, cardiologist required here electrical   activity from these tips of these catheters now  many different designs and shapes. But what it   is in the at the end of the day, it is a point by  point measurement. And it’s a lengthy measurement,  

It’s time consuming because they have to  reposition the catheter. And you have to   assume that there’s reason that this patient is in  a stable as soon as it is irregular and chaotic.   They cannot obtain reliable measurements. So it  is really only applicable in patients that have  

A stable, abnormal rhythm. Nevertheless, you can  obtain very nice maps from patients see a patient   that is an A procedure and has been tricky attack  Ikaria you can see here, two maps one was obtained  

On the on the epi card, the outside of the heart  and one was obtained on the undercard of the heart   and the inner surface. And these two recordings  were obtained kind of simultaneously and and   were synchronized in time. You see this kind of  rotating wave pattern and this is a wave pattern  

That shouldn’t be that it is abnormal, and that  causes irregular beats or irregular contractile   function. And it’s it’s circulating around this  area here where there’s presumably a scar in this   patient. So this patient had a myocardial infarct.  And then what can happen is that these waves get  

Caught there and they kind of circulate around  these infarcts. However, they can also be much,   much more complex rhythms. And you can see here an  excised Picard on the left side that was excised   at the Masters University in the Netherlands.  And they you can see very nicely how chaotic.  

This is hard contracts during ventricular  fibrillation. And on the right side here,   this is a rabbit hole that we have imaged  in our lab during ventricular fibrillation   that we induced electrically. Now we’ll slow down  this video for now, and I hope it plays smoothly,  

You can see now overlaid action potential waves  in pink, which correlate with this mechanical   contraction at the heart exibit trim and trigger  formulations. So here we have a measurement of   these chaotic leaf parents obtained on the  surface. Another example, how fast and how  

Irregular the contractions can become. And this is  a very extreme example of a technology regulating,   there’s almost no contractor activity and more.  This is why venture preparation is so dangerous,   there’s no blood flow any longer. So we can  in a laboratory setting excise hearts and keep  

Them alive for roughly one day. And do imaging  experiments with these hearts, we have fused   them with liquid called tyroid solution, which  is essentially water plus salts plus sugar and   oxygen to keep the pH level at a level where it’s  supposed to be. And then we apply something that  

Is called retrograde perfusion, we pump blood,  this solution yeah retrograding into the heart,   it closes the valves and it goes into the  coronary vessels and perfuses the heart and   therefore can be kept alive for many, many hours.  So this is our imaging setup that we have built  

Here at UCSF. You can see the centerpieces here  this imaging chamber, inside of the chambers,   this liquid and the intact heart. The heart  can also be seen here in 12. video images,   these images are acquired simultaneously at very  high speeds 500 images per second by these cameras  

That are here on this table. And on the left side,  you can see a commercial ultrasound system that   is also integrated into the immune system. And  its ultrasound system records three dimensional   volumetric images of the heart of this place where  you can see here, a rabbit heart beating in our  

Tank. This is the same rabbit heart and this is  the ultrasound transducer here at the bottom. It’s   a 2d matrix array transducer that produces between  25 and 100 volumes per second. Again, this is a   drawing here of of these different camera images,  these cameras, cameras are calibrated. And we were  

Able to reconstruct the entire surface of the  ventricles with 12 cameras that are synchronized   and calibrated. And then we cross register the  optical reconstructions that we can make with the   cameras with the ultrasound data so that we have  structural imaging data plus functional imaging  

Data that we acquire optically, because optically  we do not only image the surface of the art, but   we have recent dice and these resin dice are then  excited with this green light on the left side,   you can see here 48 LEDs are also integrated into  this imaging setup. And they illuminate the heart  

From all sides evenly and excite fluorescent dye  which then emits a particular wavelength one the   red, and this this initial light and carries  information that we can measure and from which   we can extract action potential waves. And this  year now is one such measurement during the normal  

Heartbeat sinus rhythm. You can see these are 3d  reconstructions with relatively high resolutions   to heart contracts. And you will also notice if  you watch closely, that there’s a slight decrease   in intensity, or in slow this video now Don,  again we have added voltage sensitive fluorescent  

Dye. And this dye indicates action  potential waves or voltage changes. I don’t know if you can see that on Zoom, you  may or may not see it, I can see it pretty   well on my screen, there’s a slight decrease  in I will now amplify this decrease. This is  

The routine processing step that we do we extract  the signal by simply amplifying it over time. And   you can see here the action potential wave front  in black saw this activation occurs in multiple   sites in the ventricles due to this Purkinje fiber  system that injects regexes excitation and several  

Sites. We can also measure them accordingly  mechanical strain, which you can see here is   the area change in red that is a decrease in area  change, and blue is of dilation or increase. So   that we are able to measure this is the result  of many many years of work. This technique is  

Called optical mapping and it is almost 50 years  old. In the 70s. The first measurements were done   with was voltage sensitive fluorescent dyes  and people demonstrated that it is possible   to measure actual potential waves. And then this  technique really had a had its heydays in the 90s,  

Where people using a single camera were able to  provide the first measurements of ventricular   fibrillation and these wave phenomena in hearts  and isolated hearts. However, they performed these   measurements with pharmacologically contraction,  inhibited hearts and in the past 10 years, I and  

Other people have contributed or developed either  with with which it is possible to track the heart   and extract the sickness from beating hearts. And  so there are I would say 99% of all publications   that were done many 1000s of publications were  done with these pharmacologically contraction  

Inhibited hearts. And since 2016 17, roughly,  there are now more and more publications coming   out where this compound called blebbistatin  is stepped out of the experiment. And we can   now study for the first time, mechanics  and electrics at the same time. And also,  

What is kind of rare in our field is that people  use multi camera systems such as our system in   order to reconstruct a 3d surface of the heart. So  right now, as far as I know, this measurement that  

I showed to you is the only one of its kind. This  is now a measurement of ventricular fibrillation,   you can see that the heart is moving very  slightly, almost not at all. And you can   appreciate he also these chaotic wave parents  that we can observe now on the across the surface  

Of the house, they are spiraling they’re rotating.  And that now begs the question, what what is this?   What what are these dynamics? What is cardiac  fibrillation? This is a very old question that   has fascinated many people for many, many years.  And in the 60s, chemists, physicists and chemists  

Who I also worked in gutting and in Germany, came  up with this hypothesis, okay, I know that in the   so called blues of simultaneously you chemical  reaction, I see these spiral waves and these   virus must be related to cardiac fibrillation.  Spyros are ubiquitous in nature. There are many,  

Many different examples and either biology  or in chemistry. This is an example why I   saw them here in the wild in California. And  there are many, many other examples where you   can observe spiral bass in nature. And these  are our reaction diffusion systems. Turns out,  

They have all very similar equations, different  compounds that become depleted or regenerated   and that creates these these patterns. So how can  these rotating parents be created? Or how do they   emerge in the heart in particular, they were very  early experiments roughly 100 years ago, where  

Somebody cut out a piece of a heart and stimulated  in such a way that they were able to see rotating   waves circulating in this in this ring of cardiac  muscle tissue. And that was for a very long time  

Than the central hypothesis, there must be the  circuits in the heart that sustain this persistent   activation. But since Valentin Krinsky We also  believe that this happens here in this tissue. So   if you activate cells in such a fashion here that  there’s an open end of the wave, that can emerge  

In the real heart. Or if you keep this part here  temporarily refractory activate this part and this   following happens. This wave is able to rotate  around its open end and this is a spiral wave and   and the central mechanism in the heart It drives  hardware disorders, tacky arrhythmias. This is a  

Cardiac cell culture where you can appreciate that  this wave pattern really exists in 2d at least.   And this is a recording made by Flavio Fenland,  you also look at Georgia Tech, they really see   here, the voltage and the calcium rotation of  wave that are stationary and then degenerate  

Into more complex wave patterns over time. These  wave patterns are surprised surprisingly robust,   they can be sustained and highly an isotropic and  very complex geometries, you can see despite the   in the atria, there’s varying fibers and complex  geometry, but this rotating wave can live on such  

A substrate. Depending on the parameters, and  depending on your genetic makeup, and so on and   so forth physiological conditions, these waves  can have all sorts of different shapes and as   illustrated here in this three variable model,  depending on these two parameters alone, you  

Can create various different dynamical regimes of  these waves, then the mechanisms how these waves   can break up is is is manifold, there are many  different mechanisms. But one is for instance,   that these waves can interact with themselves,  this leading edge here crashes into the tail  

Of its of its own tip arm and then can break up  this wave. And this is also shown here. They are   these breathing instabilities that can last and  further down the road cascade into chaos. This is   another illustration this wave propagates through  tissue that is damaged, the white tissue is as not  

Supporting this wave that will end it accordingly  it can lead to heterogeneity and breakup. So   heterogeneity in general can promote our revenues.  And now in 3d, it becomes a little bit more   complicated. But even in entirely homogenous media  without any heterogeneity in the substrate, you  

Can have a route into chaos. You can see here a  scroll wave and the blue line is a filament of the   scroll if that’s the center around which this wave  rotates. And due to certain instabilities, these   these filaments can interact with themselves and  break up and then cause such a complex turbulent  

Wave pattern, which is also the underlying  mechanism for this wave pattern be on the right   side. So now to the part where AI and data driven  modeling can help us to better understand or   diagnose problems and disorders. We have applied  various generic deep learning techniques, such as  

Unit, for instance, to solve certain problems  in our field. One application, for instance,   is that people are interested in localizing  these regions here around which these waves   spiral or rotate, because you can imagine that  if you would remove this point, then this, the  

Center here would stop shooting out these waves.  And accordingly, this part of the heart would go   maybe eventually back into silence. So getting  rid of these points of these facing polarities   is a way of liberating art. And therefore,  automatically tracking these points is important  

And it was already shown in the late 90s, that  you can automatically identify these points,   you embed this temporal signal using a Hilbert  transform. And then in these resulting face maps,   you can compute the gradient of the face and  whenever you compute a circular integral over  

The gradients, around such a face singularity, you  get a discontinuity. And these discontinuities can   then serve as a detection mechanism to track  automatically facing layers through or across   the tissue. However, in practice, it is not easy  to do that, even with high resolution data due  

To noise and other artifacts. It is sometimes  you end up with spurious face similarities or   measurements that are simply not robust. So  you can see here in a computer simulation,   this works really nicely. But if you imagine you  work with Kathy data mapping, and you have sparse  

Measurements, only here on these points or among  these points, then the underlying measurement is   far from the ground rules and accordingly the  trajectories of these facing block points that   can deviate quite significantly here shown  on the right side from from the grassroots.

So we thought this is the perfect problem for  units autoencoder or LSDM version of a unit to   process such data. We trained such a network  here or encoding decoding convolutional neural   network with sequence of video of such data. So  this see on the left side are voltage sensitive  

Measurements. And then on the right side,  we either target discrete points directly,   or we compute face maps and in this face maps then  face similar points. And we saw that this network   can do this easily with only five snapshots,  five measurements, from the activity, even  

Sparse measurements can provide you a face map. So  it can successfully cross predict these face maps   from electrical measurements. And they are not far  away from the ground truth. And they can do that   with less than 10% of the spatial information.  And so that showed us immediately how powerful  

New networks can be for certain applications in  our field. And you can come compare that previous   success saw measurement with maybe this example  here. Once you’ve seen this energy on the right   side, it will also be much easier for you to  anticipate what this sparse measurement of that  

Image might be. And then what the network here  does is it has seen so many examples of these   dynamics that it can easily recover the underlying  dynamics from it. The overall prediction accuracy,   of course, goes down, there’s sparser and the more  noisy the data gets. But overall, we would still  

Be able to identify hear these facing lock  points. And for these rotation of parents,   across the surface of of tissue, we’ve then  applied it to our optical mapping recordings,   you can see a ventricular fibrillation and a  Picard. And we can train this network either  

On this data or on simulation data and then  instantly compute these facing loved ones. If   we were to compute these fashionable points for  from our recordings, we would need a very long,   much, much longer recording, at least maybe one  second was he over here, only a few milliseconds  

Are sufficient to compute these points. Most  interest, interestingly to us was that we were   able to train it on simulation data as shown on  the left side, and then apply it to experimental   data as shown on the right side. Even though this  data here are these dynamics that are shown here  

Are three dimensional dynamics. And they are,  what we see here is the surface wave pattern of a   three dimensional wave pattern that evolves within  the heart muscle over here on in contrast to the   simulations that we performed are really only two  these that completely different dynamics kind of,  

And of course, these computer models also not  not fitted to this real wave pattern here. But   nevertheless, it’s sufficient for the network  to perform relatively well. So you can see here   that if we train on simulation data and apply to  simulation data, we have a very high accuracy.  

And we can train on pick data and drive data,  meaning that we used isolated hearts from either   pig or rabbit still get a very high accuracy.  And if we only train on simulation and applied   to pick a rabbits, we still get a decent Angular  accuracy. The next problem that we then tried to  

Address with the following, we can image currently  with our present eyes, the 3d wave pattern, or the   projection of this wave pattern on the surface of  the heart, but these dyes do not really penetrate.   They do penetrate into the heart muscle, but  the light coming out of that muscle cannot reach  

The surface because the hardest to thick, and  therefore we don’t really know what’s going on   underneath the hard surface. And we do not have  measurements of ventricular fibrillation in 3d,   we have computer simulations, but not real data.  And we tested now in these generic toy models  

Scenarios, how well, convolutional neural network  would be able to extrapolate the three dimensional   wave pattern from two dimensional surface  measurements, you can see on the left side,   a 3d Scroll wave pattern that shoots out waves  towards the surface on the right side, you see,  

Whatever we can see on the surface. So we’re kind  of pretending this is our experimental setting,   and then trained a neural network to predict  from 2d surface measurements. So this is the   surface layer of this bike peeled off and fed  into the neural network. And we used five time  

Steps of five of these snapshots. And the target  then was the full 3d parent. And this year is a   reconstruction so you can see that works pretty  well. When we look at it from above you see,   this super superficial layers, they are all  reconstructed pretty well. But then if we zoom  

In and look at it in more detail, we see that the  construction accuracy decreases with time. I saw   the surface layers here they are sharp and crisp  and also accurate. But the deeper you go, the more  

It fizzles out and becomes less accurate. We use  diffusion models in the same way, training them to   predict either from only the surface top surface  or from the bottom surface or from both surfaces,   the three dimensional wave pattern and saw  that they perform similarly to a simple unit  

Architecture. However, if you provide them with  more data, they can perform much better than   unit. So we did a mistake kind of we we tried to  reproduce the same results that we obtained with   the unit and with unit we saw that as saturation,  if you provide unit more than five frames, let’s  

Say 10 frames 20 3050, the the network doesn’t  become better at it. And we then also stopped   with the diffusion model was five friends because  we thought it didn’t get any better with the unit   model. But here, Stan and I were able to show  that if you actually use more data and provide  

More data to the diffusion model, and with more  data, I mean, you know, these five samples that we   extracted were five snapshots of one rotation of  such a spy wave, forcing you to take into account  

How fast do these waves propagate to the surface,  and so on and so forth. And here, if you have   much, much more data that goes maybe beyond one  period of the spiral wave, then you can actually  

Decrease this error quite a bit. Nevertheless, you  can see that the deeper you go, the greater the   uncertainty and Arabic columns. And therefore  this is maybe not the best approach to try to   extrapolate these complicated chaotic dynamics  from surface observations alone. And therefore,  

Another approach is needed. And this is something  that I would discuss now in the second part of the   talk. Before I jump into that, I wanted to mention  that I told him he in 1903 came up with this   invention of the electrocardiogram and since then,  the electrocardiogram has had tremendous success  

In cardiology, everyone uses it, it’s very cheap,  it’s very effective. And you can immediately even   at home yourself can assess the state of your  heart, you can say, okay, my heart is beating   normally or all something is something is wrong,  I need to see a doctor. And it’s very cheap. So  

Therefore, I think people have never really dare  to come up with alternatives to this. The problem   was the electrocardiogram and all electrical  measurements is what I just showed to you, you can   not access the entire heart, and you cannot really  visualize what’s going on beneath the surface of  

The heart. And this focus on the electrocardiogram  has maybe kind of blended us and prevented us   from from looking at what’s already there, and the  heart beats the heart contracts, and it’s visible,   you can use an ultrasound machine, we can use MRI,  and we see the contractions of the heart, and we  

Can analyze them. And so therefore, we could  now ask the question, can we actually calculate   the electrophysiology or the action potential wave  parents that trigger the contractions of the heart   from the motion of that, and this is, you know,  illustrated in these three idealized ventricular,  

By ventricular electromechanical simulations,  you can see on the left side, this plane wave   here induces a very distinct, contractile pattern  that is distinct from the contractor pattern that   is induced by to rotating waves or by five or  more rotating waves. So it should be possible  

To compute something like that. But we didn’t have  the measurement data that could actually give us   this this certainty or this experimental evidence  that would support this hypothesis. And here,   in our setup, we have no such data that motivates  this even further, you can see here, this wave  

That propagates across the ventricles of a rabid  heart, and this weight induces a contraction that   is highly correlated with the action potential  where it’s not that everything contracts at once.   It is really that the contractor activity sets on  and and follows the action potential. And then the  

Two questions that we had initially and we still  have, and I’m trying to address this, is this   sufficient information to compute electrical  activation, if you looked at this mesh here,   is that enough? And is this mapping  between electronics and mechanics unique?

These three images here show you how closely  correlated that actually is the action potential   wave here propagating from the left to the right.  And users contractor activity over there, because   the contracts over there which was shown here and  the strain rate in which tissue is being pulled  

Towards the wave, and that tissue dilates as a  concept plants and this is a very characteristic   phenomenon that we observe over and over now  in our experiments. And this weight frontier   between dilating strain and contractile strain is  following the action potential wavefront. There’s  

A small delay that is typical for cardiac tissue  and it propagates in the same direction. So,   there is really experimental evidence that  justifies this approach. And there are more   observations that we made in the past. So here  you can see waves with your this is a recording  

That we made with the phone, mechanical waves  propagate through the heart of the solid was   treated with cardioplegic solution. And therefore,  the activity was pretty slow down and what you   can see the space this now is the paper that  I mentioned in the beginning, I studied this  

Mechanical deformation pattern in the ventricular  was in computer simulations and then also made   recordings measuring hear voltage calcium and  strain and you see here a clockwise rotating   pattern and all of these three quantities. So down  here, we I was able to compute phase singularities  

That indicate the rotational centers of these  waves for voltage, calcium and strain. And there   are there are we published in two papers that  one is a physics based approach one is a deep   learning based approach in which we try to compute  now electrical waves from mechanical deformation.  

And I will briefly talk about this year, mainly  because I wanted to highlight how much better deep   learning works actually. So the first approach is  a data simulation approach. We say system one is   the system that we want to measure. System two is  a virtual replication of that system, we introduce  

Sensors in the system that we want to measure and  controllers in the virtual replication of that   system and drive the system with the measurement  data that we have available eventually from system   one. So we can see here to come excitable media  excitable systems, system one exists system two,  

And there’s a coupling term here and this coupling  term is really only difference between the states   of these oscillators over here versus here. And  because we do sometimes explain that much better   than 1000 words, you can see that here, this  computer simulation is coupled to the psychiatry  

Measurement over here. And just constantly  receiving input from this from these sensors   over here by by the controllers that are placed in  this domain. And you see that this simulation code   evolves with the cyclotron. And we adapted this  principle and and modified it a little bit. We  

Have we know that based on our measurements, these  electrical waves and use also mechanical waves,   therefore it might be possible to do exactly  this, slightly modified instead of having in   your control term, a comparison between the  two electrical states, you can now compare  

Either an electrical and mechanical state or the  mechanical state of system one, the mechanical   state of system two, and modify the electrics in  such a way that the mechanics of the second system   match the mechanics of the first system. So that’s  shown here we have sensors in our drive system  

Are the first system that we want to measure  which measure mechanics strain, for instance,   strain rate, and they modulate the controllers  and the electrics of the second system. So here   we have a spiral wave that induces mechanical  contractions, red is contraction, glues dilation,  

We added some noise to it and then observed  that and induced electrical excitation in these   locations here, wherever contraction occurred  was a negative electromechanical delay. And   you can see that over time, this system becomes  synchronized with the first system and therefore  

We have a reconstruction of the dynamics in the  first system based on a mechanical measurement.   And then we were relatively happy that this also  works for very complex wave parents. So you can   see here comparison of the reconstructed wave  pattern from mechanics with the original wave  

Parent to apology is very similar. However,  there were quite significant differences too.   So we were happy about an 80% reconstruction  accuracy. But all of that was kind of killed   with deep learning because it worked right away  much better using simply an autoencoder for this  

Problem. So we trained an autoencoder and a unit  with pairs of mechanical deformation patterns   with electrical excitation patterns that cause  six deformation patterns. You see a spiral wave   pattern that induces together with multifiber  anisotropy this anisotropic spiral wave like  

Mechanical deformation pattern, the Folker wave  pattern, a more complex wave pattern and we use   20,000 samples of such pairs to then estimate  to electrical waves from mechanics with unseen   data. So the network architecture again was a  simple encoder decoder, we analyze displacements,  

X and y displacements in 2d which could either be  with ref with respect to an undeformed, mechanical   state or any arbitrary mechanical state, or  the previous mechanical state of the system,   and saw that this works pretty well, after a  short period of training. And after a few epochs,  

This is an example of 3d dynamics, very, very  turbulent dynamics. These dynamics induce tiny   mechanical deformations here, which were analyzed  by the network. And this is the reconstruction.   It’s visually indistinguishable from the original  dynamics. So, the complexity of the wave parents  

Really no limitation. And you can see here on the  right side, those are wattics filaments that were   computed either from the original wave parent or  from the reconstructed wave parents in black and   gray and perfectly overlap. So now the question  is, how is this applicable in patients can we use  

This to reconstruct electrical activity in  a patient who is there in in the clinic and   doing such a procedure here you can see, this  heart is beating abnormally, this patient has   ventricular tachycardia. And at the center is  the tip of a catheter. So this person performs  

This procedure here of mapping the patient, and  spends many, many minutes maybe a full hour to   obtain a 2d map of the electrical activity. But  since we are measuring this at the same time,   this ultrasound recording, we could instantly  provide this activation map if we are able to  

Compute it from the mechanics. So we perform  computer simulations, again, idealized by our   trickier computer simulations, which retain  muscle fiber architecture that is necessary in   electromechanical simulations. This massive fiber  architecture determines how the heart contracts,   but also how the waves propagate. Then one issue  was that we needed roughly at least 10,000,  

Or maybe ideally 50,000 training samples. How do  you get that many training samples and computer   simulations that are usually traditionally very  expensive. So we use sphinxes, which is smooth   particle hydrodynamics. framework, because it  provided us sufficient speeds, and we were able to  

Compute one episode here in less than 10 minutes  and could therefore over the course of a few days,   simulate enough training samples. And then this  problem becomes the following. Here we have three   dimensional point cloud of three dimensional  motion vectors, which describe the movement,  

The formation of the ventricles, the target is  a static voltage wave pattern. Again, we have   many many different examples of these pairs, and  the unit that we then use as a sparse res unit,   we use this Minkowski engine here to process  unstructured grid data and convert it into a  

Format that this unit understands. The inputs  are five frames, describing five states of the   mechanical information state of the heart,  that could in principle be extracted from   ultrasound recordings, MRI recordings, and the  target is then the electrical morphology of the   wave pattern. In the computer simulations,  we varied for different electrical models,  

Which are produced very distinct electrical  wave parents with four constitutive laws   for the mechanics. And then randomized initial  conditions model parameters, the geometries of   the tissues can either induce focal or reentrant  base, you can see here, the different anatomical   geometries that also have an influence on the  fiber architecture, and created 1000 different  

Geometries, plus five architectures and then  varied our initial conditions. So we for instance,   stimulated the heart at the bottom at the front  or the back in random positions, or induce   these different spiraling wave parents also in  random positions. And you can see here how these  

Different electrical models produce very different  qualitatively different way quantitatively   different wave patterns. Again, this these are  four examples. This is maybe a more realistic simulation that would be more comparable to  what’s what’s happening in a patient who has   a BT episode, and this is a more idealized  computer simulation. We also in space,  

Vary the model parameters accounting for spatial  heterogeneity, and overall varied randomized More   than 15 I think parameters and also included  scar tissue or heterogeneity. So here in red,   these parts of the tissue did not contract or did  not conduct. And then we were happy to see that  

This works, we can actually train such a network.  This is the ground truth electrical wave pattern   that induced this mechanical deformation pattern,  they are shown on the left, this was the input   to the network. And this is the prediction that  works for focal wave patterns, we can compute now,  

These activation maps here from these a sequence  of predictions of electrical wave patterns. This   is an activation map that was directly computed  from the sequence of electrical snapshots. And   then from this mechanical deformation computer,  this sequence down here and this activation map,  

And it’s very similar. And you can now compute  from the mechanical information of the heart   these electrical activation maps, which are  important for cardiologist because sometimes   they’re interested in where in these ectopic beats  these additional undesired beats come from. It  

Works for reentrant wave activity, also pretty  well. And these are the different accuracies   that we achieved, how much more time do I have?  Do I need to run through the remaining slides? Or how many how many more? Slides? 11? No. And I might run out of time.

Yeah, maybe you can wrap up. Okay.  I’d like to write a write up next.   Five minutes. next five minutes. Yeah. Okay, good. So this is an example where the heart  includes also scar tissue. And the prediction   nevertheless, works quite well. This is very  important, because most patients actually do have  

Myocardial infarct and accordingly, heterogeneity,  and scars. And if this method wouldn’t work in the   presence of scars, and it would be useless,  probably. So now, how do we translate that to   the clinic, we showed in computer simulations  that this works, but that can also doesn’t  

Mean that it needs to work with patients, we  have tried to apply the network that was only   trained on simulation data on such data on the  right side, and that obviously did not work. And   our approach now is to generate training data  in our experimental setup with isolated parts,  

And then see how well that could perform maybe on  the patient data or fine tune model subsequently,   further down the road with with all of  these different types of data. So this   is the experimental data that we have is really  high quality, electromechanical data of parts,  

We know us stimulate the hearts in such a way  that we have many, many different stimulation   sites and the corresponding mechanical  deformation pattern. This is just the   optical recording the red vectors indicating  mechanical information, but we also have,   of course, transmitter with mechanical data  from the ultrasound. And this is shown here,  

This is raw ultrasound data segmentation that  deforms based on the 3d motion tracking where we   perform, there’s a corresponding target than  on the surface, at least of the electrical   activity. And we are currently in the process  of fully automating these these experiments,  

In order to be able to generate 50,000 training  samples, or many, many 1000s of training samples.   So that means that we need to be able to go  into these recordings, pick certain frame   and extract the frames, reconstruct it in 3d,  cross the interest of these two recordings,  

And extract here the corresponding data and fuse  the data together. We’ve seen in other examples   that in terms of generalization, we can train  the sorry, we can train the model and simulation   domain well, and leave out one of the electrical  models and it still works pretty well. We’ve  

Applied it to significantly different geometries.  It also works in those we have borrowed data from   from collaborators who use finite element modeling  instead of SPH modeling that we use to train   the model and it also works efficiently when I  think that if we improve our of our methodology,  

It should be possible to reconstruct overall  excitation waves from mechanical deformation. Now,   the big question is, how do we get that to work in  our ex vivo imaging setup? And let me jump through   the nebulous slides here we showed that for  instance, in these two dimensional cell cultures,  

We can apply a model that was trained only on  simulation data on these experimental measurements   and get we constructions that make us hopeful  that this could actually work in practice. As an   outlook, of course, we would like to use this data  not only for predicting one thing from another,  

But also maybe to evolve and obtain a data  driven model of of the heart based on these dis   experimental data that we’re able to generate  now in our setup. So we’ve used the fusion   modeling and saw that fusion modeling can be used  to evolve project dynamics, we can generate shapes  

And waves that look like ventricles and reentrant  circuits. And I’m sure that we will also be able   to generate beating hearts, maybe even driven  by the data that we have now in our experimental   setup. So that adds now a third pillar to our  set of tools that we have the conventional  

Computer simulations. And now maybe, hopefully  soon, also, data driven modeling of curricula   for mechanics. So and I hope I didn’t exceed too  much. Thank you very much for your attention. Very nice. Very nice. Thank you so much for  the interesting talk. Ian. enjoyed it a  

Lot. Let’s have a q&a sessions. So Well, I  first want to introduce you to rob Robert   Blake at Lawrence Livermore. Rob, are you  still there? Yeah, I’m still here. Oh,   cool. So Rob has been working on the  computational model for cardiovascular   system. We have some computational  tools. Rob, do you want to introduce?

Yeah. Hi, Yan. I worked with Natalia for a long,  long time and wrote. So we have cardioid here that   can do a whole bunch of cardiac simulation stuff  you might be interested in. I also have melody  

That lets you take anything off cell ml, and  quickly generate code for it to run in chased   or whatever simulator you want. And I have a  really cool data set that you’ll want to get   access to. We did a whole bunch of simulations of  just tricky colors, and then recorded pseudo ECGs.  

And that was able to train a neural network to  go from the ECG to transmural maps on the Hga 16. Nice. Okay, yeah, we should definitely talk. Yeah. Awesome. All right. Let’s have a q&a  sessions. If you have any questions, yeah,  

Please don’t hesitate, just unmute yourself  and ask questions. I can I can start. So,   you know, you said that the measurement  can be only done on the on the surface,   right. And in order to fill the gap, you relying  on the computational model, but every patient has  

A different shape of the heart? Probably. How do  you deal with that? I mean, it’s building those   computational model. One of them will take  some time. And if you have a patient with a   different shape of the part, do you quickly do  you parameterize, the heart computation model,  

So that quickly change the shape of the  heart and run the run the heart model? Good question, I think I don’t know. I would  assume that from imaging data would have the   shape of the heart. And the question would  also be How sensitive is the solution to the  

Shape of the patient? Is it possible to use a  generic shape that represents most patients,   so that adapts slightly to the  imaging data? I’m not sure how,   how the anatomy would influence  potential solutions, those imaging data is going to give  you the shape of the internal  

Structure of the heart as well for each patient. Yeah, yeah, sure. We don’t have MRI data or  generally have MRI data or ultrasound data.   Even though ultrasound has a pretty low spatial  resolution, it’s possible to to extract at least  

The global shape of the ventricles from it with  the Atreides it’s a bit more tricky, but that’s   definitely possible you wouldn’t be able to  extract you know, final structures is especially   on the endo card. And it’s also sometimes  not easy to delineate the organ boundaries,  

But overall, we can definitely see differences in  in adult anatomy across patients and ultrasound. One of the techniques you you showed was, you  know, only the using the sun Stata. And well,   I mean, of course, do you use the computation,  3d computational model and then generate the  

Data and train the unit, for example. And then  once the unit is trained, you just, you know,   get the measurement in sparse way, you had a  particular shape of the measurements and the   location in the space on the surface.  One was the uniform is distributed,  

And the other one was the sun. How should I say,  you know, the straight line to the center? Yeah, I think you mean the Kathina mapping data, right,   that lets us there was a study that couldn’t  go back. Yeah, if you can go back. See.

This slide. Basically, my question is,  how how do you? Right? Like that sucks about last zoom in this the star shape  at the bottom right? The right one? Yeah, exactly. How do you choose that  location is it’s somewhat flexible to   choose those locations. So all of the measurements

In this is completely determined by the  manufacturer of that catheter. So this study   here, by by Ronnie at eye, she there I think,  either chose generic representations of wood,   like this geometers are similar to these  catheters, or they are directly somehow  

Created from the classical, I don’t know. But  there are either these Penta re catheters,   or these lots of catheters, and then also basket  catheters, or just different types of catheters   that are on the market. Some of them have up to  64 I think electrodes, the basket catheters, not  

All of them measure something at the same time,  but they can sense which ones contribute to the   measurement. And there are often many different  episodes that that recorded the same time. So   that’s where it comes from. And in our study, we  just used something that looks like a star. Got

It? And I think in another  point of your presentation,   you talked about the training the unit,  and then use the training unit to you know,   get the information about the  insight, not just the surface,   I mean, the measurement, the standards on  the surface, but also the internal. Yeah,

Yeah, this year. Yeah. Right. So this is, we  pretend that this is a piece of the ventricular   wall. It’s, of course, heavily over simplified.  But we were simply interested is from our from a   dynamic systems perspective, is it possible to  reconstruct very chaotic wave parents in 3d in  

3d from only surface measurements, which is  a situation which we have in our lab, we can   currently really only measure the outer surface  eppicard. But in principle, you can also measure   from the inside the undercard at the same time.  So you have two cameras, for instance, facing each  

Other and in between is the hard wall. And in that  scenario, you have two measurements, like here on   the slide. And then whatever happens within the  hardball, the question was, can we recover that   from only these two surface measurements?  On what we what we’ve learned in these two  

Studies here Standard Oil and and labor the die  from 2020 we it is possible to some extent, in this scenario like a one step your network  the neural network is trained after that   is trained for the inference stage,  do you assume that the whole surface  

Image is available as an input or only the  sparse data on the surface is available? Here we assume that the entire services  available because the scenario that we   tried to recapitulate was optical mapping. So  optical measurement, we added some noise to it  

And saw it also works with noise, no problem,  but we didn’t try out a sparse measurement.   So that would be the next step to move to  more realistic geometries and add sparsity Okay, great. I mean, we have some technology  of you know, you know, enabling that actually,  

You know, once you train the like auto  encoder or you net and then only we get   the sparse data on the surface and then try to  reconstruct the whole 3d No output data. Maybe   I can introduce to you after the talk. Yeah,  okay. Well, that’s my question. I don’t want  

To take whole time of the q&a sessions.  Is there any questions from audience over billion questions, but it’ll go weeds. Only one or two allowed? How much? How much luck have you had with face  singularities? Every time I’ve tried to track face  

Singularities in cardiac tissue? Like, it’s super  messy? To do? Absolutely. Yeah, we just gave up   and started with like, just tracking wave fronts  and measuring them as like a 40 surface instead.   Yeah. But yeah, like, under so much. And depending  on like, little tiny things are very sensitive to  

Air, and they kind of go whoo, wobbly all over  the place, and then disappear and reappear,   like continuity and fade singularity  has always been really difficult for us. Yeah, absolutely. I agree. So there might  protect ourselves that influenced that.  

So the noise and motion artifacts and optical  recordings, at least they can cause, you know,   Basinger’s to jump or disappear or something, you  have spurious very similar results are not mere,   that are just a result of the filtering. So we, we  have a protocol, I can send it to you if you want,  

That works relatively well when the signal  quality is good enough. So you can process video   data in a way that you focus on the wavefront,  rather than the wave itself. Both way works,   and you have to slightly smooth the data. And  then you remove outliers, from the normalized  

Data. So what you want to do is you want to  normalize each time series, to amplify the waves,   and then use the Hilbert transform or whatever you  need in order to embed the signal and compute the  

Face map from it. And then what is very important  is to smooth the face maps using a complex filter.   So you convert the face maps into a 2d vector  field with with a normalized amplitudes. Like   a complex number, and then filter that. And  with that technique we had, were quite like,  

It’s pretty robust. Of course, it doesn’t prevent  you from detecting face singularities that are,   you know, further down further upstream  in the processing pipeline created there,   or just simply the fact that you’re looking at a  projection of a 3d wave pattern. And these some  

Of these spirals and meander really strongly they  they have a linear core rather than a point around   which they rotate. And that can also cause issues.  And there’s some work by a group in Belgium that   came out recently where they look at that in  more detail. But it can get very messy. Yes.

Have you ever seen an arrhythmia without a face  singularity? Either linear core or point core? I know data from Flavio Fenton where he has shown  that I think, have I seen that in my experiments?

I don’t think so. Okay, because we I’ve been we’ve  been like we saw it all the time and stimulation,   it would happen, especially around scar  structures. And like, the whole face   singularity stuff just really kind of broke down  because we’re like, can’t find and we have to  

Do integrals. And we’re like half the heart.  We can’t find the in the face singularities. Yeah, the linear core is really an issue. And  that has also raised concerns with this concept   of facing law even makes sense. So the people in  Belgium, Hans Dirks, and his people, they publish  

Something last year thing where they expand this  concept of a face singularity into different   lines. And it gets also really complicated  highlighting that it is a complicated topic,   more complicated than at least just points  looking at points. I think it’s, it’s a nice  

Concept too, too, too, to look at, but I would not  overemphasize it. To describe fibrillation, it’s   in the end, it was supposed to reduce complexity,  if you look at a three dimensional wave pattern   that changes quickly in time. So for the wave  pattern, it can become very, you lose track of it.  

It’s just complicated and difficult to understand.  And therefore I thought back then and 2000s,   it was thought to help people to understand what’s  going on and that way it helps because you can   count the number of waves you can determine the  density of these waves. You can see how waves  

Interact with each other these filaments when they  touch each other and break up. That’s that’s a   nice concept. But other than that, it’s I think we  also need other to was to look at corroboration. When I see that you you’re using  unit or autoencoder type of approach,  

That is nice because it gives you some  reduced latent space dimensions and,   you know, bring the data size effectively  reduced to the smaller dimensions and but   have you tried to actually interpret that  any physical meaning on that latent space,  

The reduced dimension later in the middle of the  unit or the middle spacing in the auto encoder? Do you mean if you’ve ever used visualization  tools of what’s going on in the latent space or physical? Yeah, physical principle later, I mean,  your underlying physics, they say electrical  

Mechanical systems themselves, you know, I saw you  present his some partial differential equations   associated with it. And, you know, of course,  the data is, you know, if you use the simulation,   that data will be really high dimensional.  So after the auto encoder, it is reduced,  

And it’s, it’s quite unknown, what physical  meaning those latent space has. Maybe you can   put some meaning to it, physical meaning  to it, associated with those electrical,   mechanical, electric, electric mechanical  system. You have? Have you tried that? No,

We, that we we try to kind of verbally, you know,  talk about what what, what happens in the latent   space, maybe here, in particular with these  facing polarities, which is a simple, I think,   a much simpler problem where you only have a  scalar valued field that you transform into a  

Complex field. You have these two numbers that  define the phase angle? They are, I would say,   the latent space, what is it?  It’s that conversion, you know,   that you do with the hero transform somehow,  locally, this is much more local, I think,  

In the case of the electromechanics, you have long  reaching elastic effects. So, global motion of I   don’t know how it translates different modes of  the contraction of the of the deformation of the   heart that are in the latent space somewhere. I  mean, it’s pretty amazing when you look at these  

Simulations here that you can convert something  like this vector field on the left into a scalar,   varied, filled with complicated geometry,  relatively complicated geometry. It’s amazing and very interesting. Very interesting. Yeah. What happens to us? Right? Well, you know, our group, we tried to,  there’s a framework we developed called elastic  

Latent space dynamics, identification, meaning  that so once once you project those 3d motions,   vector field into the latent space through the  auto encoder, and you get some dynamic signal   in the middle of latent space, and we don’t  know, what’s the governing equations for that  

Trajectory data, so we try to associate that  with a some sort of differential equations,   and then try to understand what that differential  equations, what kind of meaning it has. So yeah,   maybe I can introduce that to you as  well. Okay, so I have a to do list.

Sounds great. Yeah. I would  love to talk about that. Awesome. Awesome. All right. Any  other questions from audience? Well, it’s now let’s, let’s thank  our speaker yarn for the wonderful   talk and interesting talk. I learned  a lot and hopefully we can, you know,  

Further stimuli stimulator. The collaboration  between Lawrence Livermore and UCSF. Yeah, would be great. I was very happy when  I found out about this seminar. So it   was recommended to me by Michael Gregory. Awesome. Awesome. Thank you.  Thank you. Thanks. All right. Transcribed by https://otter.ai

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