Friday, August 26, 2016

Everything's Up To Date in Kansas City

A photograph of Union Station in Kansas City, Missouri.
Union Station.
I posted the last two entries in this blog while on a trip to Kansas City to visit my parents. I didn’t grow up in the Kansas City area, but I did graduate from Shawnee Mission South High School in Overland Park Kansas, and I was a physics major at the University of Kansas in Lawrence. My dad is a native of Kansas City Missouri, while my mom moved to Kansas City Kansas when young and attended Wyandotte High School.

A photograph of the Kauffman Center for the Performing Arts, in Kansas City, Missouri.
Kauffman Center
for the Performing Arts.

We had a great visit, including a ride on Kansas City’s new streetcar, which travels a route along Main Street from Union Station, past the Power and Light District, within a few blocks of the Kauffman Center, to the River Market. We also had a great pork sandwich at Pigwich in the East Bottoms. Kansas City is booming.

A photograph of Liberty Memorial and the National World War I Museum in Kansas City, Missouri.
Liberty Memorial.
Is there any connection between Kansas City and medical physics? Yes, there is. Rockhurst University, a liberal arts college located a mile west of where my dad grew up on Swope Parkway, offers an undergraduate program in the physics of medicine, which is similar to the medical physics major we offer at Oakland University. I thought the readers of Intermediate Physics for Medicine and Biology might like to see how another school besides Oakland structures its undergraduate medical physics curriculum.

From their Physics of Medicine website:
POM Program Overview: To suit your interests and career goals the POM Program has three program choices:
  • Medical Physics Major - Major Track designed for students wishing to enter graduate school in Medical Physics
  • Physics of Medicine (POM) Pre-Professional Major - Major Track designed for students wishing to enter a Medical/Healthcare Graduate Program
  • Physics of Medicine (POM) Minor— Minor designed to complement pre-healthcare or pre-medicine program
Advantages to students of the POM Program are:
  1. Deeper understanding of physics principles and their applicability to a medical or health field career.
  2. Stronger post-graduate application to competitive health field programs.
  3. Undergraduate research opportunities – potential for capstone area or future graduate work. 
  4. Value to students of interdisciplinary study, allowing them to tie together coursework in science/math with professional goals. 
All Physics of Medicine Coursework is designed to complement the Scientific Foundations for Future Physicians Report, Report of the AAMC-HHMI Committee (2009).
Some courses specific to the program are:
PH 3200 Physics of the Body I: This course expands on the physics principles developed in introductory physics courses through an in-depth study of mechanics, fluids and thermodynamics as they are applied to the human body. Areas of study include the following: biomechanics (torque, force, motion and lever systems of the body; application of vector analysis of human movement to video), thermodynamics and heat transfer (food intake and mechanical efficiency) and the pulmonary system (pressure, volume and compliance relationships). Guest speakers from the medical community will be invited. [This course appears to cover the material in Chapters 1-3 in IPMB]

PH 3210 Physics of the Body II: This course is a continuation of Physics of the Body I with a concentration on the cardiovascular system, electricity and wave motion. Areas of study include the following: cardiovascular system (heart as a force pump, blood flow and pressure), electricity in the body (action potentials, resistance-capacitance circuit of nerve impulse propagation, EEG, EKG, EMG), and sound (hearing, voice production, sound transfer and impedance, ultrasound – transmission and reflection). In addition, students complete a guided, in-depth, individual investigation on a topic pertinent to Physics of the Body. Guest speakers from the medical community will be invited. [Approximately Chapters 6, 7, and 13 in IPMB. PH 3200 and 3210 together are similar to Oakland University’s PHY 325, Biological Physics]

PH 3240 Physics of Medical Imaging: This course focuses on an introduction to areas of modern physics required for an understanding of contemporary medical diagnostic and treatment procedures. Topics include a focus on the physics underlying modern medical imaging instruments: the EM Spectrum, X-Ray, CT, Gamma Camera, SPECT, PET, MRI and hybrid instrumentation. In this course, students learn about the physics involved in how these diagnostic and therapeutic instruments work as well as the numerous physics and patient factors that contribute to the choice of instrument for diagnosis. There will be field trips to local hospitals and medical imaging facilities and invited guest speakers. [Chapters 15-18 in IPMB; similar to OU’s PHY 326, Medical Physics]

PH 4400 Optics: This course covers both the geometric and physical properties of optical principles including optics of the eye, lasers, fiber optics, and use of endoscopy in medicine. Students will complete a final optics research project in which they relate content learned to an area of optics research. [Chapter 14 in IPMB. We have no comparable course at OU. We offer a standard optics class, but with no biomedical emphasis. This class intrigues me.]

PH 4900 Statistics for the Health Sciences: This course introduces the basic principles and methods of health statistics. Emphasis is on fundamental concepts and techniques of descriptive and inferential statistics with applications in health care, medicine and public health. Core content includes research design, statistical reasoning and methods. Emphasis will be on basic descriptive and inferential methods and practical applications. Data analysis tools will include descriptive statistics and graphing, confidence intervals, basic rules of probability, hypothesis testing for means and proportions, and regression analysis. Students will use specialized statistical software to conduct data analysis of health related data sets. [Nothing exactly like this in IPMB. At OU, we require all medical physics majors to take a statistics class, taught by the Department of Mathematics and Statistics.]

PH 4900 Research in Physics of Medicine: Independent student research on coursework from Physics of Medicine Program. Students will choose topic from Physics of Medicine Program coursework to investigate further and prepare for presentation submission. This course will serve as a capstone course for Medical Physics and Physics of Medicine Pre-Professional Majors. [I am a big supporter of undergraduate research. At OU, medical physics majors can satisfy their capstone requirement by either research or our seminar class.]

MT 3260 Mathematical Modeling in Medicine: Students will build mathematical models and use these models to answer questions in various areas of medicine. Topics may include: Epidemic modeling, genetics, drug treatment, bacterial population modeling, and neural systems/networks. [IPMB is focused on mathematical modeling. I teach PHY 325 and 326 as workshops on mathematical modeling in biology and medicine.]
The Rockhurst physics of medicine minor looks like an idea I am tempted to steal. Their requirements are:
To complete the Physics of Medicine Minor:
Prerequisites: one year of introductory/general physics and Calculus I (complete in first two years)
Upper Division Courses: complete 4 upper-division POM courses (12
  • PH 3200: Physics of the Body I (3 Hours, Offered Fall Semester Odd years) 
  • PH 3210: Physics of the Body II (3 Hours, Offered Spring Semester even years)
Choose 2 from the following:
  • PH 3240: Physics of Medical Imaging (3 Hours, Offered Spring Semester Odd Years) 
  • PH 4400: Optics (3 hours, Offered Fall Semester Even Years) 
  • MT 3260: Mathematical Modeling in Medicine (3 Hours, Offered Fall Semester Even years)
  • PH 4900: Statistics for the Health Sciences (3 Hours, Offered Spring semesters)
An OU version might be Biological Physics (PHY 325) and Medical Physics (PHY 326), plus their prerequisites: two semesters of introductory physics and two semesters of calculus.

A photograph of the Nelson Art Gallery in Kansas City, Missouri
The Nelson Art Gallery.
I enjoy my trips to Kansas City because there is a lot to do and see there, from the Nelson Art Gallery to Crown Center to the Liberty Memorial and the National World War I Museum. I remember in high school attending shows at the Starlight Theater in Swope Park, and watching many Kansas City Royals baseball games at Kauffman Stadium (where I saw George Brett play in the World Series!). The Truman Library is in nearby Independence Missouri.

A photograph of the Country Club Plaza in Kansas City, Missouri.
The Country Club Plaza.
I didn’t expect to find a hub of medical physics education in Kansas City, but there it is. In addition to the Rockhurst program, the Kansas University Medical Center has a CAMPEP-accredited clinical medical physics residency (while driving on I-35, I could see cranes putting up a new KU Med Center building), and the Stowers Institute, less than a mile north of Rockhurst and just east of the Country Club Plaza, has a strong biomedical research program. As the song says, Everything's Up To Date in Kansas City.

A photograph of thousands of people in Kansas City celebrating the 2015 Royals World Series Championship.
Kansas City celebrating the 2015 Royals World Series Championship.

Friday, August 19, 2016

How to Explain Why Unequal Anisotropy Ratios is Important Using Pictures but No Mathematics

Ten years ago, at the IEEE Engineering in Medicine and Biology Society Annual Conference in New York City, I presented a paper titled “How to Explain Why Unequal Anisotropy Ratios is Important Using Pictures but No Mathematics.” Although it was only a four-page conference proceeding, it remains one of my favorite papers.
I. Introduction 

The bidomain model describes the electrical properties of cardiac tissue. The term “bidomain” arises because the model accounts for two (“bi”) spaces (“domains”): intracellular and extracellular. Both spaces are anisotropic; the electrical conductivity depends on the direction relative to the myocardial fibers. Moreover, the intracellular space is more anisotropic than the extracellular space, a condition referred to in the literature as “unequal anisotropy ratios.” This condition has important consequences for the electrical behavior of the heart.

Many papers describe the implications of unequal anisotropy ratios. The mathematical derivations and numerical calculations in these reports emphasize the consequences of unequal anisotropy ratios, but they often fail to explain physically why these consequences occur. For example, Sepulveda et al. discovered that during unipolar stimulation, depolarization occurs under the cathode but hyperpolarization exists adjacent to it along the fiber direction. The hyperpolarized regions affect the mechanism of excitation, the shape of the strength-interval curve, and the induction of reentry. Yet, when I am asked why the hyperpolarization appears, I find it difficult to give an intuitive, nonmathematical answer.

In this paper, I try to answer the “why” questions that arise from the bidomain model. I present no new results, but many old results are clarified. My hope is that the reader will develop the intuition necessary to understand qualitatively how cardiac tissue behaves, without having to resort to lengthy mathematical derivations or numerical calculations.
Parts of this article have worked their way into Intermediate Physics for Medicine and Biology. For instance, the article explains how a wave front propagating through cardiac tissue creates a magnetic field. This analysis is reproduced as Problem 19 in Chapter 8 on biomagnetism.

Problem 50 in Chapter 7 examines the transmembrane potential induced in cardiac tissue when an electric shock is applied in the presence of an insulating obstacle. I love how this example highlights the importance of unequal anisotropy ratios.
Consider an insulating cylinder in an otherwise uniform tissue with straight fibers (Fig. 7). An electric field is applied from left to right. Far from the insulator, the current is in the x-direction and is distributed equally between the intracellular and extracellular spaces. As current approaches the insulator, it turns left to circle around the obstacle. The current then is flowing approximately perpendicular to the fibers, so most of the current will be extracellular. As the current turns right to flow once again in the x-direction, it will be parallel to the fibers and will again be distributed more or less equally between the two spaces. As current leaves and then reenters the intracellular space, it causes depolarization and then hyperpolarization. The transmembrane potential distribution surrounding the insulator is even in y and odd in x. The result is the complex pattern of polarization surrounding an insulator in cardiac tissue during electrical stimulation.
A figure from “How to explain why unequal anisotropy ratios is important using pictures but no mathematics,” showing how polarization is caused by an insulating obstacle.
Fig. 7. Distribution: Polarization caused by an insulating obstacle.
This figure explains the results observed in [18].
The role of theoretical analysis in biology and medicine is to make predictions that can be tested experimentally. My former PhD advisor John Wikswo and his team used optical mapping to measure the transmembrane potential around an obstacle during a shock. Their results are shown in the picture below. The bottom line: the prediction and the experiment are consistent. Physics works!

Optical mapping to measure the transmembrane potential around an obstacle during a shock, from: Woods et al. "Virtual Electrode Effects Around an Artificial Heterogeneity During Field Stimulation of Cardiac Tissue" (Heart Rhythm, 3:751-752, 2006).
Optical mapping to measure the transmembrane potential around an obstacle during a shock,
from: Woods et al. (Heart Rhythm, 3:751-752, 2006).
One graduate student, Marcella Woods, was involved in both of the projects I mentioned. She performed the theoretical analysis of the magnetic field produced by wave fronts in cardiac muscle under my direction when I was on the faculty of Vanderbilt University. After I left, she worked with Wikswo and carried out the experiments shown above.

Friday, August 12, 2016

Have We Reached the Athletic Limits of the Human Body?

The Olympics are in full swing this week, giving us in the United States a brief respite from our nasty presidential campaign. As you might guess, I view the Olympics through the lens of biological physics. One question that physics can help answer is: Have we reached the athletic limits of the human body? Can sprinters run faster and faster, or have we reached the physical and physiological limit? Can pole vaulters vault higher? Can long jumpers jump longer? Can swimmers swim quicker? An article in last week’s Scientific American by Bret Stetka tries to answer these questions.
At this month’s summer Olympic Games in Rio, the world's fastest man, Usain Bolt—a six-foot-five Jamaican with six gold medals and the sinewy stride of a gazelle—will try to beat his own world record of 9.58 seconds in the 100-meter dash. If he does, some scientists believe he may close the record books for good. Whereas myriad training techniques and technologies continue to push the boundaries of athletics, and although strength, speed and other physical traits have steadily improved since humans began cataloguing such things, the slowing pace at which sporting records are now broken has researchers speculating that perhaps we’re approaching our collective physiological limit—that athletic achievement is hitting a biological brick wall.
The article cites a 2008 paper by Mark Denny, the author of Air and Water, a book often cited in Intermediate Physics for Medicine and Biology. Denny suggests that there are limits, and we are closing in on them.
Are there absolute limits to the speed at which animals can run? If so, how close are present-day individuals to these limits? I approach these questions by using three statistical models and data from competitive races to estimate maximum running speeds for greyhounds, thoroughbred horses and elite human athletes. In each case, an absolute speed limit is definable, and the current record approaches that predicted maximum. While all such extrapolations must be used cautiously, these data suggest that there are limits to the ability of either natural or artificial selection to produce ever faster dogs, horses and humans. Quantification of the limits to running speed may aid in formulating and testing models of locomotion.
Yet Denny was not overly cautious in his paper. He predicted minimum times for many races, including the 100 m dash. Stetka writes
Bolt hopes to beat the researcher’s [that is, Denny’s] fastest predicted 100-meter dash time of 9.48 seconds. Unfortunately, according to Denny, the now notably older sprinter may have missed his chance. The sprinter was a chasm ahead of the pack in a semifinals race at the 2008 Beijing Olympics when he slowed up before crossing the finish line. “I think had he kept going at full speed he would’ve set an all-time, unbeatable world record,” Denny speculates.
Then Stetka quotes Denny as saying
“When I published my paper, the feedback I got was that this was going to destroy the Olympics,” he recollects. “That’s like saying the 1962 Brazilian soccer team was the best ever so no one’s ever going to watch the World Cup again. But if Bolt can run the 100 in 9.47 seconds and beat my prediction, then hats off to him. I think there’s always going to be the lure of ‘maybe someone’s going to do better.’”
I plan to watch the Olympics and see if humans can run faster than ever before. I’m a big fan of Mark Denny, but I’ll be routing for Bolt (or Gatlin) to beat Denny's prediction.


P.S. A long frustrated sigh goes to Michael Phelps and the other USA swimmers engaged in “cupping” therapy pseudoscience. Oh, where is Bob Park when we need him! Ignore the quackery and gibberish and focus on the swimming.

Friday, August 5, 2016

Zapping Their Brains at Home

A screenshot of Zapping Their Brains at Home, by Anna Wexler.
“Zapping Their Brains at Home,”
by Anna Wexler.
A couple weeks ago, Anna Wexler published an article in the New York Times titled “Zapping Their Brains at Home.”
Earlier this month, in the journal Annals of Neurology, four neuroscientists published an open letter to practitioners of do-it-yourself brain stimulation. These are people who stimulate their own brains with low levels of electricity, largely for purposes like improved memory or learning ability. The letter, which was signed by 39 other researchers, outlined what is known and unknown about the safety of such noninvasive brain stimulation, and asked users to give careful consideration to the risks.
I worked on brain stimulation when at the National Institutes of Health, and Russ Hobbie and I analyze neural stimulation in Intermediate Physics for Medicine and Biology. So what is my reaction to these do-it-yourselfers? My first thought was “Yikes…this sounds like trouble!” But the more I think about it, the less worried I am.

We are talking about transcranial direct current stimulation, which uses weak currents applied to the scalp. I have always been surprised that such tiny currents have any effect at all; see my editorial “What Does the Ratio of Injected Current to Electrode Area Not Tell Us About tDCS?” (Clinical Neurophysiology, Volume 120, Pages 1037–1038, 2009). My advice to the do-it-yourselfers is not so much “be careful” but rather “don’t get your hopes up.”

Of the four coauthors on the letter in Annals of Neurology, the only one I know is Alvaro Pascual-Leone, who I worked with while at NIH and who we cite several times in IPMB. Below I list the main points raised in the letter:
  • Stimulation affects more of the brain than a user may think 
  • Stimulation interacts with ongoing brain activity, so what a user does during tDCS changes its effects 
  • Enhancement of some cognitive abilities may come at the cost of others 
  • Changes in brain activity (intended or not) may last longer than a user may think 
  • Small differences in tDCS parameters can have a big effect 
  • tDCS effects are highly variable across different people 
  • The risk/benefit ratio is different for treating diseases versus enhancing function
What do I think of do-it-yourselfers in general? I have mixed feelings. Heaven help us if they start fooling around with heart defibrillators, which could be suicidal. For transcranial magnetic stimulation, I think the biggest risk would be the construction of a device that sends kiloamps of current through a coil. I have always thought that TMS is more dangerous for the physician (who often holds the coil) than for the patient. Moreover, the induced current in the brain is larger for TMS than for tDCS. I would be wary of do-it-yourself magnetic stimulation. But for D.I.Y.ers using relatively low-level electrical current applied to the scalp, if someone educates themself on the technique and follows reasonable safety recommendations, then I don’t see it as a problem.

Wexler ends her letter
The open letter this month is about safety. But it also a recognition that these D.I.Y. practitioners are here to stay, at least for the time being. While the letter does not condone, neither does it condemn. It sticks to the facts and eschews paternalistic tones in favor of measured ones. The letter is the first instance I’m aware of in which scientists have directly addressed these D.I.Y. users. Though not quite an olive branch, it is a commendable step forward, one that demonstrates an awareness of a community of scientifically involved citizens.
If you want to read more by Wexler, look here and here.

My final, and admittedly self-serving, advice to the D.I.Y.ers: go buy a copy of Intermediate Physics for Medicine and Biology, so you can learn the scientific principles behind this and other techniques.