Weeks 6 & 7: Great experience

I've decided to post the manuscript of the uncut version of my immersion presentation, as I will not be able to present this in Ithaca.

Well, here it is:

[This photo was taken at the Fourth of July Fireworks in South Street Seaport, at the bottom tip of the Manhattan Island.]

My Immersion assignment was with my mentor, Dr. Jonathan Weinsaft, in the Cardiology Department. As the primary focus of my immersion experience, I consulted Jonathan to have my immersion experience revolve around noninvasive aspects of the cardiovascular system.

Here is what I learned from the first few weeks of my immersion program:

When patients visit the Cardiology department complaining of chest pain, one of the first scans done is the Echocardiography. This is a standard procedure that uses ultrasound, in which the technologist acquires different 2D ultrasonic images, ranging from Triscupid valve Apical 4 and 2-Chambers. I was told that there are about 70 or more Echos done every day at the NYP.

Of particular note is the transesophageal ECHO, which gave out much nicer ultrasound images compared to standard ECHO. The above photo you see is that of the transesophageal probe, which is about a meter long, and that which a patient sedated for a couple of hours had to swallow.

I also got to see several CATH Labs, in which I observed the insertion of catheters for performing x-ray angiography. There are about 20 of these each day.

Nuclear stress tests are associated with SPECT imaging, and they are used to examine myocardial perfusion. Most of what I saw were the three different kinds of stress tests;
Treadmill, Adenosine, and Dobutamine

I followed Jonathan in the Clinical ICUs, and learned a lot about the importance of spending time examining the cases of each patient. As this is the intensive care unit, the patients are among those who have the most critical cardiac conditions. While I got to ask many questions to the fellows, residents, and medical students about the various instruments, terminologies, and tasks that are done in the ICU, it was also tough to see some patients pass away during the week that I followed Jonathan in the rounds.

Here is a slide that I pulled off from Google; it shows a CT angiography, in which we see a clear extension of the coronary artery in this specific case. In addition to seeing Jonathan examine these on the workstation, I got to learn from one of the fellows how to read CTs. This was a very interesting experience, as CT reading seems to be more of an art, than a systematic task that can be automated by a computer.

Finally, I got to do a bit of Magnetic Resonance Imaging. This is a photo from a scanner on 70th Street. Shawn, a fellow Immersion student, is in the scanner and was my first human volunteer for MRI scanning. At one point during Shawn's brain scan, as I was getting used to the different scanning parameters on the computer control screen, I completely forgot to press the scan button for quite a while. Shawn was unknowingly in the scanner for over 20 minutes without anything happening, and experienced a long and tiring scan due to the ineffective performance of a novice scan technician. (sorry Shawn) However, we did get some cool images.

I’d like to now describe my project, which revolves around the Cinematic (CINE) imaging of the left ventricle.

First, the left ventricle is perhaps the most important of the four chambers in the cardiac system, as it is the primary chamber that pumps the blood to the body. From what I have experienced, most of the coronary angiography, stress perfusion/myocardial performance, and diagnostic imaging focuses on the examination of this chamber.

CINE imaging refers to the cinematic imaging, and cine-CMR (SSFP) provides high spatial resolution imaging and is widely accepted as a diagnostic standard for assessment of left ventricular systolic function and chamber volumes.

In order to use this as an effective tool, the workstations are equipped with a software called ReportCARD, which has a manual tracing feature, which is widely applied for quantification of cine-CMR. This software is used to segment the left ventricle chamber and myocardium at systole and diastole. However, there are limitations to manual tracings.

The major Limitations of Manual Tracing are: that it is time consuming. That reproducibility is variable. That it eliminates data; because of time constraints, only end-systolic and end-diastolic volumes are quantified, so all other cardiac phases are ELIMINATED.

I watched Jonathan perform time trials of these tracings for an upcoming paper, and he took on average about 5 to 7 minutes, and sometimes 10 minutes for each case.

The big question we asked is Can we do better? And the answer is Yes.

The LV METRIC segmenter is a program developed by Mr. Noel Codella of WCMC, and it is an automated system that can quickly segment the CINE images saved as SA FIESTA on the workstations, and acquire volumetric data in a lot less than 5 minutes per case. Citing the performance of the segmenter from Mr. Codella’s paper, we know that this tool demonstrates robust performance in getting an accurate volumetric data of the chamber. Our project will take advantage of the segmenter's ability to perform full volumetric assessment. This opens up new possibilities of not only examining the LV chamber contraction (i.e. systole, ejection fraction) but also the patterns of LV chamber relaxation (i.e. diastole).

Now let us talk about diastole. Is diastolic function important? Yes, for
- prognosis
- treatment
- etiology of heart failure

Q. How do we typically assess diastolic function?
A. MUGA, which stands for Multiple Uptake Gated Acquisition, is an Nuclear study that measures the derivative of pressure; dP/dt. We can also use Echo and look at mitral inflow patterns. The MRI has been used for assessment of diastolic function as well; for example with tagging.

The problem with tagging is, it requires additional dedicated imaging (adding to exam time, more breath-holds, inability to analyze large datasets), and the computational analysis of change in myocardial thickness by tagging is nontrivial, as it needs to thoroughly account for spatial and temporal geometry.

Let me explain a little more about the Left Ventricle Diastole. With a full volume curve, we can make the following plot, as in the above. We can then identify the diastole region to the peak of the filling curve. One parameter we are interested is the volume change over time; ie. taking the derivative. Now let's zoom in to the derivative of the diastole region.


In the derivative of the diastole region, we observe that the following is analogous to the Mitral Inflow pattern obtained from Echo. In a healthy case, (above) we can observe the E-wave being larger than the A-wave.


In the following diseased case, we see some abnormality, where the E and the A wave profiles look clearly different. We note that our full-volume assessment is able to generate the same curves as the Mitral Inflow patterns.

Here's an illustrative example of why our study is important. Let us consider the following cases:

Consider two cases with TPFR is the “time to peak filling rate”, and is measured from the end of systole to the time of peak filling; in other words, to the moment with the largest slope value.

Notice that for each of the two cases, the TPFR is quite different; but the traditional ejection fraction method would identify these cases to be both healthy.
For the PFR, the peak filling rate taken by the maximum value of the derivative curve, we notice a substantial difference between the two volumetric curves. This would be a likely misdetection case had we used the Ejection Fraction method to diagnose the cardiac condition.

In order to analyze this data, my project was to develop a software that efficiently sorted, filtered out any private information, and would allow easy analysis of all the cases to be examined for an upcoming study. In MATLAB environment, I developed a Graphical User Interface called LV Analyzer.
Here is what the block panel of the Graphical User Interface LV Analyzer looks like. This runs on MATLAB, and feeds in the raw data from the workstation, processes and sorts the data accordingly, displays the features necessary for the study, and saves it as an output file that can be opened by a spreadsheet program, like Excel.

I will continue to develop the LV-Analyzer after the Summer Immersion program, and plan on using the software to analyze data for an upcoming study.

I'd like to finish my presentations by thanking the following people who have made my immersion experience truly a great one.

That's All She Wrote

Well, after taking time to mull over my final week at Weill, I can finally offer some parting thoughts on my immersion experience. Incredible. The opportunity that we were presented with is so unique and so beneficial that I can still hardly believe what I just spent the past 7 weeks doing. As a chemical engineer by training, all of my medicinal knowledge has been fairly limited to almost a decade’s worth of time as an EMS worker on an ambulance corp. I knew, while useful in small, contained scenario’s, this knowledge wasn’t passable to transform myself into a biomedical engineer. I find it impossible to be a successful biomedical engineer if there is a complete disconnect between one’s studies and one’s field.

What I’ve truly come to realize is that this 7 week crash course in medicine has exponentially increased my knowledge in my newly adopted field. The awareness of new terminology, treatments, and the field of medicine in general has come so far from my first week to my final weeks that I can hardly believe it. I also have had enough OR time to make any first or second year medical student jealous. It is still as mind boggling to me about the things surgeons can do in the OR as it was 6 weeks ago. This is why I find one of the final cases I was able to observe seems an appropriate way to end my blog posts.

On my final day I was privy to really see the advances in biomedical technology and how it is one of the largest driving forces shaping the medical field. The case I’m speaking about was that of a patient who had previously had an extensive hemangioma tumor removed from their brain. This type of tumor, while benign, can grow and cause severe problems (as one can imagine) if not treated. This patient had undergone surgery some time ago to remove part of the tumor and, due to its extensiveness, had to have part of their skull removed at the time. This missing portion of the skull was replaced by a mesh frame which sadly got infected shortly thereafter and had to be removed. For the past number of months the patient lived normally expect with a giant depression where their skin met their brain without any hard protective barrier. It was at this juncture in the patient’s care that I met them and watched as the original neurosurgeon reopened the skull to try to resect more of the tumor and then fit them with a new biomedical device. What was truly amazing here was how much the technology had already improved in such a short period of time. This meant that instead of a mesh cage molded to fit the patient’s head shape during surgery, a polymer made of Poly(methyl methacrylate) would be custom built beforehand using a rapid prototyper to make the 3d replica. This device was then anchored into the patient’s remaining skull and Dr. Spector made some very precise incisions to move the skin over to cover the new device. After watching this surgery and imaging the improvement in this patient’s quality of because such a device exists really brought the whole experience full circle.

In the end summer immersion had its ups and downs, its ridiculously long days (more than I would like to count), but when all is said and done it was an experience I wouldn’t trade for anything. Good luck to all the incoming 1^st year PhDs, I hope you find the same fulfillment with your immersion experience at Weill as I did, because your time there is really what you choose to make out of it.

End of this story but the beginning of many more

While Summer Immersion term is over, my project most definitely is not. Over the past few weeks I’ve been spending less and less time in the OR and the clinic and more time behind a computer learning statistical methods and doing statistical analysis. My project has been to use a database created by medical research assistants to determine if there is a correlation between the rate of complications after radical cystectomy and the type of cystectomy being performed (robotic vs. open). The crazy thing is that in all my weeks at Weill I had yet to see an open cystectomy. It seems that Dr. Scherr is somewhat defined for his ability and proficiency with robotic cystectomies. Just yesterday I had my first opportunity to see an open cystectomy, so I popped into the OR to see what my analysis was really evaluating. The surgery definitely seemed more difficult without the magnification of the robotic camera, but the reality is that many surgeons still prefer to perform this surgery open because they are more proficient behind the table rather than at a robotic console. The specific case Dr. Scherr was performing was an open cystectomy because the patient had had a partial nephrectomy before and they knew there would be scar tissue to deal with that they were unaccustomed to with the robot.

I say that my research project is definitely not over for a couple of reasons. First, I will continue to analyze and tweak our model over the next few days to see if I can improve the model fit. We had to use multinomial logistic regression to analyze the data because we are looking at a binary outcome (complication or no complication). Additionally many of our predictor values are ordinal or nominal rather than scalar. The five variables we choose to evaluate (we being a few residents and I) are body mass index (BMI), age, Charlson score, ASA score (American Society of Anesthesiologists score) and the type of cystectomy (robotic or open). I first looked for a basic correlation between the type of cystectomy and occurrence of complications using crosstabulation and Pearson chi-squared tests. This showed that there is a significant correlation between the two, but we needed to ensure that was not just an artifact of other factors. For example we needed to prove that it is not just the younger, leaner, healthier patients that are undergoing robotic cystectomies. To show this more rigorously I needed to use multivariate regression but with these nominal and categorical variables. In the end I think I developed accurate models, but only more time and more critical evaluation by the residents will tell. Secondly this project is far from over because our analysis is limited by the fact that we only have around 200 patients. At first I thought this was more than sufficient, but as I continued to do my analysis and needed to categorize these cases the sub-grouping became ever smaller making statistical analysis very difficult. So this evaluation will just be the foundation that they can build upon in years to come as they continue to have a more robust database of cases.

Finally I just want to remark on the miracle of life. Last Friday Jen and I had a wonderful opportunity to observe a C-section. Not only were the patients gracious at having additional people in the room but the surgeon was also keen to teach us. Before we ever entered the OR he had us read-up on why this patient was having a C-section. This woman had a bicornuate bicollis uterus (which is to say she had a septum in her uterus dividing it in two). A C-section was required and might need to be performed along the length of the uterus rather than at the base because her two uteri are narrower than a standard woman’s uterus. In this case though, they were able to get the baby out of the base of pregnant uterus and could even show us the amazing capability of the uterus to expand with a baby since this woman had one pregnant and one non-pregnant uterus. So not only had we walked in to see a C-section, but we also walked in on a high risk pregnancy that had come to full term with a healthy baby. Additionally this was the first child for these parents and they didn’t know the baby’s sex, so it was a very exciting OR!

Yeah!! The Last Week of Summer Immersion

Wrapping up the data I have collected until now and catching the last chance to visit the OR I haven't been before, these two things are basically what I have been doing in the last week. Even though I knew that I won't be able to finish the great plan of website within six weeks a long time ago, even though I knew that there are numerous small miracles and drama happening somewhere in this hospital I wouldn't be able to learn, even though I still have tons of questions and ideas in my mind about the PC measurement, I had to face to fact that: the last week of this summer immersion program is coming to an end.

In retrospect, six weeks is really too short for me to get enough insight into the hospital. This morning when I watched the whole process of C-section for the first time and maybe the last time in my life, the strong contradiction between the bloody scene and the super happy expression on the face of the mother was still a great shock to me. As an undergraduate in biology, I would never be be touched by a bloody experiment and hardly moved by an affecting drama. Because of that, I underestimated the power of the inevitable combination of the two in hospital before I could realize it. Though for many times I reminded myself not be too involved in personal emotion about one single case, I know it is actually very hard. How could one find a simple righteous principle in the mergence area of natural and social science? How could the hybrid of research institution and social facilities be easily judged on right and wrong?

Knowing this, I am very happy that this program could offer me this chance to have a little touch to the knowledge of this super complicated system during the short six weeks under such circumstances. Perhaps many years later, most of the medical terms I learned at this moment would be gradually erased from my memory. Nevertheless, there are definitely some scenes, some people and some words I once came across in this summer would remind me from time to time many different aspects I used to neglect when studying healthcare in the lab. They will also remind me what kind of things I should pay attention to besides the improvement of technology in my career as a bioengineer.

Knowing this, I am not regretful that I have only been here for six weeks. Actually, on the other hand, I found myself can be helpful to someone in hospital right in the last week. When the assistant of doctor came over to me in panic asking about some net questions, when the medical student also came over to ask me some math conceptions in references, I finally felt that I little "nobody" BME PhD could also do "something" here!