5th week in Plastics

This past week I was able to see quite a few interesting cases. Monday morning I listened to a lecture on hand trauma and then watched and residents discussed how to approach specific cases. This lecture turned out to be very useful because we had a hand trauma case this week. A garbage man was unlucky enough to get his hand caught in the garbage compactor. He was brought into the OR in the hopes of salvaging his index finger which had been almost completely crushed. The surgeons removed the debris from the finger (including the crushed bone) and tried to piece back together what they could. A microscope was used to attach nerves, veins, and arteries that had been severed. With all the effort, the surgeons were still very skeptical that the finger would be able to survive because there appeared to be no blood flow in the tip of the finger.

In addition to plastics cases, I also attended a couple Neuro cases. This was very interesting to watch. The surgeons entered the brain through the nasal cavity, removing the septum in order to have a clear view of the interior. Although miniaturized, the tools were the same basic tools used during many of the plastics cases. The patient had a pituitary tumor which was removed through the nasal cavity with a device that worked by simply pinching off a small portion at a time. Once the tumor had been excised, the septum was reconstructed from tissue taken from the abdomen of the patient.

On Friday, I decided to see something other than surgical intervention to help patients. I went on rounds in the NICU with Mike and Dr. Frayer. I found that in the NICU the doctors are very concerned with the overall patient . In my experience thus far, many surgeons are there to treat one main problem, which may even be the root of a lot of other problems, but in the NICU, the health of the patient overall seems much more important. The main discussion of each patient was that of overall function. With all the advancements in medicine to date, it is amazing to me how important simple bodily functions matter. Calorie intake, weight gain or loss, peeing, pooping, and all the basic functions of living are of utmost importance in the NICU. Spending one day to complete rounds in the NICU was a very worthwhile experience.

Additionally, I want to discuss one case that I have been able to see progress through my time here. When I first arrived, the patient was in the hospital awaiting surgery. He had previously had surgery on his neck to stabilize some of his vertebrae and hardware was used to complete the surgery. You can see the hardware in the first image (metal on either side of the spine). An infection set in at the site of the surgery, and the patient was transfered to Plastics. I didn't realize prior to my time here that Plastic Surgeons work a lot on wound care and thus often receive patients from other services once infections are found. In this case, Dr. Spector took the patient to the OR to irrigate and debride the wound. He then closed the wound in layers to provide more stability to the wound. To do this each layer must be separated from the above tissue and then closed over. You can see in the second image how this was completed. Additionally, Jackson Pratt (white plastic in wound) drains were left in the patient to allow for drainage of fluids from the wound site. This prevents pockets of fluid for forming underneath which must then be remove with a needle. An image of just the drain is also shown (from: http://courses.vetmed.wsu.edu). The drains are cut to fit in the wound bed and then a small hole is made away from the incision and the drain is threaded through the hole. Once there is no longer large amount of fluid being drained, the JP is simply removed by pulling it through the insertion site. The ability to observe the fluid as it drains from the site is helpful because it can be an early indication of infection. Since the surgery the patient has been able to return home and the wound is nearly completely closed with minimal problems.

Of PC Flow and Moving Woes

Ok, I'll admit it. I'm not in New York City. Earlier this week I returned to Ithaca to catch up on the latest cow tipping action, and to move out of my apartment. Three days later, my entire life is in a series of carefully sealed and labeled boxes, my movers still haven't shown up ("Today! We promise. We promised yesterday? Well we mean it this time!"), and I'm sitting on a living room box typing a BME blog entry on my cell phone. That has to count for something, right?

Any ways, back to my project. We haven't fully worked out the automatic segmentation yet, as Noel is still tweaking a few things, but from the look of it, the comparisons between the Phase Contrast derived measurements and the manually segmented magnitude images are intriguing. It appears that while they have a somewhat high correlation (0.95 or greater), one always seems higher than another.

From these early results, it is easy to see that the two forms of "ground truth" may not even agree! How, then, can we ever judge the accuracy of te automatic segmention algorithm? Perhaps it will be similar to the PC flow analysis, but not the magnitude based measurement. And if so, is this more accurate than i it was the other way around?

An interesting question that, for me in any case, remains unsolved. Looks like this phone doesn't seem to get along with PubMed. Alas...

Neurological Surgery

Deep Brain Stimulation for Parkinson’s treatment

One particularly interesting surgery I was able to observe this week was a deep brain stimulation procedure to treat a Parkinson's patient. Parkinson’s disease results from a lack of dopamine being produced in the substantia nigra, and results in four possible symptoms – tremor of a limb, slowness of movement, rigidity, and poor balance. The patient I observed seemed to exhibit all of these symptoms, with bilateral tremors and rigidity in her arms and legs.

Since no treatment is currently able to prevent or slow the progression of Parkinson’s disease, all treatments aim to treat the symptoms to make life easier. The current options include medication, surgical lesioning, or deep brain stimulation. One common medication is L-dopa, which is converted into dopamine in the brain. Surgical lesioning involves removal of part of the brain that is abnormally active, such as the globus pallidus (pallidotomy). Deep brain stimulation (DBS) can involve the thalamus, subthalamic nucleus, or globus pallidus, all of which are important in the pathway for movement control. It is thought that DBS helps by pacing abnormally firing cells in these regions.

Dopaminergic pathways. Left side is for a normal brain, and right side is for a Parkinson's patient. Red arrows indicate an inhibitory effect and blue arrows indicate an excitatory effect. http://en.wikipedia.org

Prior to the surgery, Dr. Kaplitt had determined the location of the subthalamic nucleus in the brain by taking an MRI, and had mapped the stereotactic coordinates of this structure. He drilled two holes in the skull and inserted electrodes in the locations indicated by the coordinates. Electrical activity was recorded for a depth range of approximately 20 mm using a 7 micron electrode tip. Using the recordings, the doctors were able to distinguish approximate borders between different areas in the brain - thalamus, subthalamic nucleus (STN), and substantia nigra. It was clearly visible that certain cells in the STN corresponded temporally with the tremors exhibited by the patient. Dr. Kaplitt inserted stimulating electrodes and applied a voltage across these and observed the physiological response of the patient. In certain locations, the applied stimulus was able to visibly decrease tremor and reduce rigidity in the patient's arms and hands. Two days after this procedure, the patient would have a permanent system implanted, much like the one shown in the figure below. The doctor suggested that the deep brain stimulation system in combination with medications would be able to better control the patient's symptoms in the future.

Deep brain stimulator. www.epda.eu.com

The use of focused ultrasound for theraputics in medicine

This is my last week here at Weill, and over the immersion thus far I have gotten to see many, many... many different types of surgeries and medical-clinical procedures. With my little blue note book and cell-phone camera I have been taking notes and jotting down ideas.

At first I was going to focus my research project on neurological drug delivery using ultrasound. This was related very closely to my Ph.D. research and fit with my mentor Dr. Riina, but after seeing all that was available to be here at the hospital and the willingness of clinicians to work with me, I have been able to broaden my view and study.

I also admit that after seeing laproscopic bladder and prostate surgeries, and the tools the doctors use I was inspired to think up some new applications of ultrasound in the treatment of diseases.

BACKGROUND

Acoustical techniques have been used in a variety of situations to enhance medical treatments. For example, high intensity focused ultrasound (HIFU) has been used to ablate and liquefy tissues, and past and current studies are being conducted to assess the use of HIFU as a more complete surgical tool for minimally invasive therapy. Focused ultrasound is beginning to be assessed as a feasible way to deliver drugs to neurological tissues via selective disruption and permeablization of the blood brain barrier (BBB). Drugs that once could not cross the BBB because of molecular weight and hydrodynamic radius are now able to permeate into the neurological tissue with the application of ultrasound. Ultrasound has also been used in other applications such as gene therapy and drug activation, and for further information on therapeutic ultrasound one can read the Nature Drug Discovery Article "Healing sound: the use of ultrasound in drug delivery and other therapeutic applications.

The above image shows the enhancing effects of ultrasound on non-invasive drug delivery into tissue. Shown in yellow is the drug perfusion by diffusion mechanisms alone, shown in green is the enhanced delivery of drug with ultrasound The image x-axis is distance into the tissue and y-axis is the amount of drug potentially delivered.

POTENTIAL USES OF THERAPEUTIC ULTRASOUND

My experience from watching surgeries, talking with clinicians, and reviewing literature on PubMed, has created many potential uses for enhanced drug delivery using ultrasound in the clinical setting.

1. Neurosurgery:

a.) After tumor removal drugs are delivered locally, or the space is filled with a gliadel BCNU wafer. The application of ultrasound may potentially enhance drug diffusion from the locally delivered chemotherapy, thus increasing the chemo's effectiveness.

b.) In trying to fix neural aneurysms the most common techniques are either to pinch it off, or filling it with a coil. The use of ultrasound may be able to activate a locally delivered filling agent, or it may be used to target drugs to reduce the growth and shrink the aneurysm.

Things that must be considered to apply this technique are the following: getting the acoustic energy to the specific location, not damaging the tissue in its pathway and developing a re-usable minimally invasive mechanism.

Possible solutions are:

I. To produce an array that attaches to the head and is able to target the specific location (Like the acoustic version of the gamma knife). Existing mapping technology with MRI/image guided procedures could be used to simplify development

II. Use a high-power catheter based acoustic probe e.g. intravenous ultrasound, that may be guided to the place of interest. This however requires the development of new piezoelectric materials, that can produce large acoustic outputs with small surface area.

The above image is a potential acoustic therapeutic helmet.

2. Prostate Surgery:

Removal of the prostate may be

A stapler device

It’s a good opportunity to see different type of medical devices in the OR. I thought a needle was a must when closing a wound, but I was wrong. A surgical stapler makes the anastomosis easy and fast.

A Transverse Anastomosis stapler (TA) is such a device that closes the bowel lumen while the dissection and excision of the specimen are in progress. The underneath picture is a sample of TA.



It’s very easy to use this devise. Basically, the doctor first puts the jaw of stapler gun at the right position. Of course this is the most important step. Fully squeeze the handle to load the staples, and fully squeeze the handle again to fire the staples. I think even myself can conduct these three steps as long as I know where to put the jaw.


Actually, the jaw is the magic part. It contains one double staggered row of titanium staples. After the staples are fired, the hook up area will look like this.


There are also some other features of this stapler gun. The staple unit can be replaced. It can be reloaded 7 times for a total of 8 firings. Safety Lockout prevents an unloaded or improper loaded stapler gun to be used. For me, it is really amazing to see how the mechanics can be applied to facilitate the surgical operation.

Calcium Score: Part 1

Everyone has heard of atherosclerosis; it is the term for the cardiovascular disease that is the outcome of atherogenesis (the accumulation of plaque in the arteries). An atheromatous plaque forms due to atheroma or the accumulation of lipoproteins (cholesterol) and connective tissue inside the arterial wall. Shear stress and other factors that thin the arterial wall can sometimes cause the wall containing the ‘vulnerable’ plaques (or soft plaques) to rupture. If the rupture clogs the coronary arteries, this can result in ischemia or even a heart attack (infarction of cardiac tissue).

With age, if the soft plaques do not rupture, the layer between them and the vessel wall near the lumen can undergo microcalcification, and in general, create calcium deposits in the arterial wall. As a result, the amount of calcium in the coronary arteries is an established number for identifying the severity of coronary artery disease. The number is commonly referred to as ones calcium score and anyone who gets a CTA (CT angiography) done can obtain their calcium score from their physician. However, one should be cautious since the distribution of the calcium in the coronary arteries (whether the calcium is diffused or focused) also plays an important role. Furthermore, the number does account for the number of soft plaques or vulnerable plaques, which in fact pose a greater risk since they have the potential to rupture. Evidently, there is no index out there that quantifies the vulnerability of plaques since they are difficult to identify using most imaging modalities or software. In fact, the software that I’ve been using only quantifies calcium in the coronary arteries.

In particular, I’ve been using software developed by GE called Smart Score (figure) to assign patients a calcium score. That is, I’ve been highlighting the calcium in the arteries using CTA and differentiating the calcium for the left anterior descending artery (LAD), left circumflex (LCX), and the right coronary arteries (RCA). Doing this is pretty straight-forward. I just click on a button labeled LAD if I want to highlight the calcium deposits in the LAD, RCA for calcium deposits in the right coronary artery, and LCX for deposits in the left circumflex. The software automatically segments the calcium deposits within the region I highlight using a simple thresholding algorithm. When I do this for all of the transverse slices of the heart, I record 8 numbers. One number corresponds to the overall volumetric score or the total volume of calcium in the coronary arteries, and three other numbers for the volume in the LAD, LCX and RCA. Similarly, an older and more commonly used number for calcium scoring, known as the agatson number, is recorded. The agatson number, unlike the volumetric score, scales the area of segmented calcium in each slice by the average Hounsfield value/ brightness of the segmented region. I believe this older method was developed to account for partial volume effect in CT images. In fact, even though the volumetric score is more accurate, the agatson score is still used due to legacy. I guess it doesn’t really matter. I have looked at both numbers for 200+ patients, and I can say that they don’t differ by a concerning amount.


I guess some of you might be wondering why I’m collecting this data in the first place. I’ll discuss the details of that later this week.

Automatic Segmentation: Some Ideas

During the last meeting, I was asked if I had any ideas on how to approach the problem of automatically segmenting the different features of the heart. While I currently lack the background to speak definitively about the "low level" technical details of creating such an algorithm, I have several usability ideas that pertain to how the program will eventually be used by the clinician. I believe that, while the accuracy of the algorithm is certainly an extremely aspect of the program's design, the interface itself must be intuitive enough to be used easily while conforming to the user's expectations in operation and implementation. In many ways, the interface itself is just as important as the algorithm behind it.

1. Users like control
Currently, the algorithm developed by Noel Codella is highly automated, but in doing so, takes much of the control away from the user. To operate the program, the user must simply identify the left ventricle in one slice of the cine MRI with a single click. The algorithm handles the rest. But to an experienced clinician who is used to performing all of the tasks manually, this degree of automation is a little disconcerting. I believe adding an option for the user to "tweak" the algorithm's segmentation decisions would lessen this sense of detatchment. While it is debatable whether a computer or a human can provide the best segmentation decisions, giving the option to perform manual corrections would make the user far more comfortable in using the program.

2. Users like feedback
As much as everyone loves to hate the little status bars the creep across the screen while we perform tasks on the computer, they are essential. I never really realized this until I saw the automatic segmenter in action. The program, while relatively fast, requires up to 30 to 45 seconds to fully complete segmentation after the initial user input. Unfortunately, there is no visual indication concerning the program's progress during this time. In every trial thus far, the program has finished successfully every single time it has been run, so it would seem that a status bar would serve little purpose other than to provide a little visual entertainment for the user. In reality, I've found that this has been one of the major complaints about the program's current implementation. Users like feedback about what the computer is doing!

These are all pretty minor suggestions that have little to nothing to do with the algorithm itself, but I feel changes such as these would make the program far more user friendly and will make it more likely for the program to be used in an actual clinical setting in the future.