Friday, October 9, 2009

Steven Chu, Biological Physicist

Readers of the 4th edition of Intermediate Physics for Medicine and Biology may wish to see examples of physicists who have contributed to biology. One excellent example is Steven Chu, who until recently was professor of physics and professor of molecular and cellular biology at the University of California, Berkeley. Chu describes his biological physics research on his Berkeley website:
We apply single molecule techniques such as fluorescence resonance energy transfer, atomic force microscopy and optical tweezers, we study enzyme activity, and protein and RNA folding at the single bio-molecule level. Systems being studied include how the ribosome reads m-RNA and manufactures proteins, how vesicles fuse into the cell wall at the synapse of neurons, how cells adhere to each other via adhesive molecules, and how RNA molecules fold into active enzymes.
If you want to hear Chu talk about his biological physics research, watch this video on YouTube.

 Steven Chu asks What Can Physics Say About Life?
https://www.youtube.com/watch?v=lUR3WgVh-Hc
Some of his best known biological physics papers, published while on the faculty at Stanford, are:
Steven Chu exemplifies how physicists can contribute to our understanding of biology.


....Oh, did I forget to mention something? Chu is best known for his work on the “development of methods to cool and trap atoms with laser light,” for which he shared the Nobel Prize in Physics in 1997. He is currently Secretary of Energy in the Obama administration, and is leading the US effort to move away from fossil fuels and toward alternative energy sources, thereby combating global warming.

Who says we don’t have wonderful role models anymore?

Friday, October 2, 2009

Are Static Magnetic Fields Dangerous?

Are static magnetic fields dangerous? This question has recently taken on added importance because a European directive is limiting a worker’s exposure to the strong static magnetic field in a magnetic resonance imager, thereby impeding research with MRI. A recent article by Denis Le Bihan on medicalphysicsweb.org asserts that
those limits could end up preventing the technique from being used—just when European scientists are starting to lead the world in ultra-high-field (UHF) MRI magnet research. The initially proposed limits will immediately put the brakes on progress and, moreover, be a big blow to companies that make MRI scanners and magnets, such as Siemens, Philips, Bruker and Magnex. These firms could end up being unable to meet the growing global demand for clinical UHF MRI scanners, the high fields from which could boost the potential of MRI for healthcare and biomedical sciences, particularly for neurological applications.
Voodoo Science, by Robert Park, superimposed on Intermediate Physics for Medicine and Biology.
Voodoo Science,
by Robert Park.
Physicist Bob Park, the author of Voodoo Science and the weekly newsletter What’s New, writes
MAGNETIC FIELDS: THE PRECAUTIONARY PRINCIPLE IN ACTION. According to Denis Le Bihan at the CEA-Saclay Centre, a European directive to prevent workers from being exposed to high magnetic fields could severely impact research into Ultrahigh-Field MRI which shows great promise particularly in neurological applications. It is particularly frustrating that limits on static magnetic fields resulted from the paranoia surrounding EMF, which was associated with everything from power lines to cell phones, Wi-Fi, Bluetooth, and other wireless devices. As I pointed out in an editorial in the Journal of the National Cancer Institute eight years ago, “there will always be some who will argue that the issue has not been completely settled. In science, few things ever are.”
Are these limits justified? Based on my knowledge of biomagnetism, I think not. There are few known mechanisms by which a static magnetic field can have a significant biological impact, except in unusual cases such as a person with a ferromagnetic medical implant, or in some animals (such as magnetotactic bacteria) that are believed to sense magnetic fields, presumably by the presence of ferromagnetic or superparamagnetic nanoparticles (magnetosomes). Russ Hobbie and I discuss the possible effects of weak magnetic fields in Chapter 9 of the 4th edition of Intermediate Physics for Medicine and Biology.

Denis Le Bihan is a leader in the field of MRI, known for his development of diffusion weighted imaging. He is director of NeuroSpin, a French institute aimed at developing and using ultra high field Magnetic Resonance to understand the brain. I knew Denis when we were both working at the National Institutes of Health in the 1990s. He was a close collaborator with my friend Peter Basser, and together they developed diffusion tensor imaging. (Incidentally, one of their early papers on this topic just received its 1000th citation in the citation index!) Let us hope that Le Bihan’s important research is not interrupted unnecessarily by misguided government regulations.

Friday, September 25, 2009

Cochlear Implants

Russ Hobbie and I discuss the ear and hearing in Chapter 13 of the 4th edition of Intermediate Physics for Medicine and Biology. Last Wednesday, Russ attended a colloquium at the University of Minnesota titled “Bionic Hearing: The Science and the Experience,” presented by Ian Shipsey of Purdue University. The talk was about cochlear implants, at topic we mention briefly in Section 7.10 on Electrical Stimulation. You can download the entire powerpoint presentation from the colloquium. Shipsey’s story is itself inspirational. On his website he writes “I had cochlea implant surgery in November 2002 at the Riley Hospital for Children in Indianapolis, IN. The surgeon was Professor Richard Miyamoto. The device was activated in late December. I am now able to hear my daughter for the first time and my wife for the first in 12 years.

In order to understand cochlear implants, you need to understand how the ear works. For a short lesson, you should watch an absolutely incredible video on YouTube. This animation is a wonderful example of what can happen when science education meets modern technology, and it was selected by Science Magazine as the first place winner in its 2003 Science and Engineering Visualization Challenge. Don’t miss it; especially you Beethoven fans!

Auditory Transduction.
You can learn more about cochlear implants by viewing a video of a lecture by Richard Miyamoto titled “Cochear Implants: Past, Present, and Future,” which you can download from a website about cochlear implants maintained by the National Institute of Deafness and Other Communication Disorders, one of the National Institutes of Health. More information is available on a Food and Drug Administration webpage. Also interesting is a National Public Radio report about cochlear implants.

When I worked at NIH in the 1990s, I used to attend the Neural Prosthesis Program workshops held in Bethesda every fall. I recall listening to the researchers each year report on how they were developing these incredible devices to restore hearing. From those workshops, I gained a great appreciation for cochlear implants, and I have come to view them as a prototypical example—along with the cardiac pacemaker—of how physics and engineering can contribute to medicine.

Friday, September 18, 2009

More on "Is Computed Tomography Safe?"

The December 7, 2007 entry to this blog was titled “Is Computed Tomography Safe?” As is often the case with such a difficult question, the answer is yes and no. No—there are risks associated with any exposure to ionizing radiation, so no procedure is entirely safe. Yes—in most cases the risks are small enough that the benefits outweigh the risks. In order to answer this question more precisely, a large scale study with nearly one million patients was conducted over three years. The conclusions were reported in the August 27 issue of the New England Journal of Medicine. The abstract of Fazel et al.’s paper “Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures” (NEJM, Volume 361, Pages 849–857, 2009) is reproduced below.
Background: The growing use of imaging procedures in the United States has raised concerns about exposure to low-dose ionizing radiation in the general population.

Methods: We identified 952,420 nonelderly adults (between 18 and 64 years of age) in five health care markets across the United States between January 1, 2005, and December 31, 2007. Utilization data were used to estimate cumulative effective doses of radiation from imaging procedures and to calculate population-based rates of exposure, with annual effective doses defined as low (less than 3 mSv), high (greater than 20 to 50 mSv), or very high (greater than 50 mSv).

Results: During the study period, 655,613 enrollees (68.8%) underwent at least one imaging procedure associated with radiation exposure. The mean (±SD) cumulative effective dose from imaging procedures was 2.4±6.0 mSv per enrollee per year; however, a wide distribution was noted, with a median effective dose of 0.1 mSv per enrollee per year (interquartile range, 0.0 to 1.7). Overall, moderate effective doses of radiation were incurred in 193.8 enrollees per 1000 per year, whereas high and very high doses were incurred in 18.6 and 1.9 enrollees per 1000 per year, respectively. In general, cumulative effective doses of radiation from imaging procedures increased with advancing age and were higher in women than in men. Computed tomographic and nuclear imaging accounted for 75.4% of the cumulative effective dose, with 81.8% of the total administered in outpatient settings.

Conclusions: Imaging procedures are an important source of exposure to ionizing radiation in the United States and can result in high cumulative effective doses of radiation."
To help put this study in context, the NEJM published an accompanying editorial by Michael Lauer (“Elements of Danger—The Case of Medical Imaging,” Volume 361, Pages 841–843). Lauer writes that
Because the use of ionizing radiation carries “an element of danger in every . . . procedure,” we need to adopt a new paradigm for our approach to imaging. Instead of investing so many resources in performing so many procedures, we should take a step back and design and execute desperately needed large-scale, randomized trials to figure out which procedures yield net benefits. This approach would require leadership and courage on the part of our profession, our opinion leaders, and the research enterprise, but were we to insist that all, nearly all, procedures be studied in well-designed trials, we could answer many critical clinical questions within a short time. Because we will continue to be uncertain of the magnitude of harm, an accurate understanding of the magnitude of benefit is a moral imperative.
In Chapter 16 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the risk of radiation. While we do not provide a final answer regarding the safety of CT, we do outline many of the important issues one must examine in order to make an informed decision. The safety of computed tomography and other diagnostic imaging procedures will continue to be a crucial question of interest to readers of Intermediate Physics for Medicine and Biology. I will try to keep you posted as new information becomes available.

P.S. Thanks to Russ Hobbie for calling my attention to this paper. He reads the New England Journal of Medicine more than I do.

Friday, September 11, 2009

A New Homework Problem

While in Minneapolis last week, attending the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society, I had the pleasure of co-chairing a session with Professor Michael Joy of the University of Toronto. Joy has done some fascinating work on measuring current and conductivity in biological tissue using magnetic resonance imaging. His research inspired me to write a new homework problem for Chapter 8 of the 4th edition of Intermediate Physics for Medicine and Biology.
Problem 21.5 The differential form of Ampere’s law, derived in Problem 21, provides a relationship between the current density J and the magnetic field B that allows you to measure biological current with magnetic resonance imaging [see, for example, Scott, G. C., M. L. G. Joy, R. L. Armstrong, and R. M. Henkelman (1991) “Measurement of Nonuniform Current Density by Magnetic Resonance,” IEEE Transactions on Medical Imaging, Volume 10, Pages 362–374]. Suppose you use MRI and find the distribution of magnetic field to be

Bx = C (y z2 – y x2)
By = C (x z2 – x y2)
Bz = C 4 x y z

where C is a constant with the units of T/m3. Determine the current density. Assume the current varies slowly enough that the displacement current can be neglected.
To solve this problem, you need the result of Problem 21 in Chapter 8, which asks the reader to derive the differential form of Ampere’s law from the integral form given in the book by Eq. 8.11. If I were teaching a class from the book, I would assign both Problems 21 and 21.5, and expect the student to solve them both. But for readers of this blog, I will tell you the answer to Problem 21 (ignoring displacement current), so you will have the relationship needed to solve the new Problem 21.5: curl B = μ0 J. The curl is introduced in Section 8.6. If you don’t have the 4th edition of Intermediate Physics for Medicine and Biology handy, take a look in a math handbook for information about how to calculate the curl (or see Schey’s book Div, Grad, Curl, and All That).

The story of how you measure B using MRI is interesting, but a bit too complicated to describe in detail here. In brief, a magnetic resonance imaging device has a strong static magnetic field about which nuclear spins (such as those of hydrogen) precess. The magnetic field produced by the current density modifies the static magnetic field, causing a phase shift in this precession. This phase shift is detected, and the magnetic field can be deduced from it. Technically, this method allows one to determine the component of the magnetic field that is parallel to the static field. Obtaining the other components requires rotating the object and repeating the procedure. See Chapter 18 for more about MRI.

Send me an email (roth@oakland.edu) if you would like the answer to the new Problem 21.5.

Enjoy.

Friday, September 4, 2009

31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society

I’m posting this blog from Minneapolis, Minnesota, where I am attending the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society. The theme of the conference is “Engineering the Future of Biomedicine,” and there are many fascinating talks and posters that would interest readers of the 4th edition of Intermediate Physics for Medicine and Biology. Conference chair Bin He and his colleagues have put together a great meeting.

My friend Ranjith Wijesinghe and I have a poster later today about the “Effect of Peripheral Nerve Action Currents on Magnetic Resonance Imaging.” We analyzed if the magnetic field of action currents can be used to generate an artifact in an MRI, allowing direct imaging of biocurrents in the brain. There has been a lot of interest, and many publications, on this topic recently, but we conclude that the magnetic fields are just too small to have a measureable effect.

Last night, I got to hear Earl Bakken give a talk on “The History of Short-Term and Long-Term Pacing.” Bakken is a giant in the history of artificial pacemakers, and is the founder of Medtronic Corportion based in Minneapolis. He talked about the early years when Medtronic was a small electronics laboratory in a garage. He recommended a 10-minute video on YouTube, which he said told his story well. He also quoted one of my favorite books, Machines in our Hearts, a wonderful history of pacemakers and defibrillators. Tonight a social is being held at the Bakken Museum, “the only museum of its kind in the country, [where you can] learn about the history of electricity and magnetism and how it relates to medicine.” For a guy like me, this is great stuff.

Earl Bakken; Ready, Fire, Aim!

So far, the presentations are fascinating and inspirational. I must admit, the students who attend these conferences always stay the same age as I grow older. I don’t think these meetings used to be this exhausting for me. As that old Garth Brooks song says, “the competition’s getting younger.” They are also getting more diverse. The speaker who welcomed us to the Bakken talk said that in just a few years, Americans will be a minority within the IEEE Engineering in Medicine and Biology Society. This is not difficult to believe, after seeing researchers from so many countries attending this year.

As I survey all the research presented at this meeting, I am proud that so much of the underlying science is described in Intermediate Physics for Medicine and Biology. I am more convinced than ever that Russ Hobbie and I have written a book that will be of great value to future biomedical engineers.

Friday, August 28, 2009

Resource Letter MPRT-1: Medical Physics in Radiation Therapy

When Russ Hobbie and I were preparing the 4th edition of Intermediate Physics for Medicine and Biology, we tried to update our book with the most recent references. But, inevitably, as time passes the book becomes increasingly out-of-date. How does one keep up with the literature? This blog is meant to help our readers stay current, but sometimes more drastic measures are required. Fortunately, the American Journal of Physics publishes “Resource Letters,” in which the author reviews important sources (mainly textbooks and research articles) on a particular topic. In the September 2009 issue of AJP, Steven Ratliff of Saint Cloud State University published “Resource Letter MPRT-1: Medical Physics in Radiation Therapy” (Volume 77, Pages 774–782, 2009). The abstract is reproduced below.
This resource letter provides a guide to the literature on medical physics in the field of radiation therapy. Journal articles, books, and websites are cited for the following topics: radiological physics, particle accelerators, radiation dose measurements, protocols for radiation dose measurements, radiation shielding and radiation protection, neutron, proton, and heavy-ion therapies, imaging for radiation therapy, brachytherapy, quality assurance, treatment planning, dose calculations, and intensity-modulated and image-guided therapy.
I highly recommend this Resource Letter for anyone interested in radiation therapy. Particularly useful is Ratliff’s concluding section “Recommended Path Through the Literature.”
The best single reference for a newcomer to the field is Goitein (Ref. 14). It is clear, up to date, readable, complete, and gives a good explanation of what medical physicists do. For a person who does not want to enter the field but is just curious or needs to get some information and does not want to spend any money, a good place to start is the free on-line book by Podgorsak (Ref. 153). Van Dyk (Ref. 17) is a good place to start for those who want a clinical emphasis. The book by Turner (Ref. 91) has good problems (some with answers) and covers many aspects of the subject.

For those wanting to make a career of Medical Physics, a small but good starting library would consist of Goitein (Ref. 14), Hendee et al. (Ref. 30), Johns and Cunningham (Ref. 15), Khan (Ref. 16), Podgorsak (Ref. 153), Turner (Ref. 91), and van Dyk (Ref. 17). Khan is more useful once you have learned the material. If you have more money, you could add Attix (Ref. 19) and Podgorsak’s book on radiation physics (Ref. 26). Cember and Johnson (Ref. 92) is a good addition if you are interested in the health-physics aspects of radiotherapy.

If you were restricted to one book and wanted to learn as much as possible, then the handbook of Mayles et al. (Ref. 18) is worthy of serious consideration.
The references Ratliff cites in his conclusion (less than 10% of the 183 publications included in the entire Resource Letter) are listed below.
14. Radiation Oncology—A Physicist's Eye View, Michael Goitein (Springer Science+Business Media, LLC, New York, 2008).

15. The Physics of Radiology, Harold Elford Johns and John Robert Cunningham, 4th ed. (Charles C. Thomas, Springfield, Illinois, 1983).

16. The Physics of Radiation Therapy, Faiz M. Khan, 3rd ed. (Lippincott Williams and Wilkins, Philadelphia, PA, 2003).

17. The Modern Technology of Radiation Oncology—A Compendium for Medical Physicists and Radiation Oncologists, Vols. 1 and 2, edited by Jacob Van Dyk (Medical Physics, Madison, WI, 1999 and 2005).

18. Handbook of Radiotherapy Physics—Theory and Practice, edited by P. Mayles, A. Nahum, and J. C. Rosenwald (Taylor & Francis, New York, 2007).

19. Introduction to Radiological Physics and Radiation Dosimetry, Frank Herbert Attix (Wiley-VCH, Weinheim, Germany, 1986).

26. Radiation Physics for Medical Physicists, E. B. Podgorsak (Springer-Verlag, New York, 2006).

30. Radiation Therapy Physics, William R. Hendee, Geoffrey S. Ibbott, and Eric G. Hendee, 3rd ed. (Wiley, Hoboken, NJ, 2005).

91. Atoms, Radiation, and Radiation Protection, James E. Turner, 2nd ed. (Wiley, New York, 1995).

92. Introduction to Health Physics, Herman Cember and Thomas E. Johnson, 4th ed. (McGraw-Hill Medical, New York, 2009).

153. Radiation Oncology Physics: A Handbook for Teachers and Students, edited by E. B. Podgorsak (International Atomic Energy Agency, Vienna, 2005). (www-naweb.iaea.org/nahu/dmrp/pdf_files/ToC.pdf)
By the way, if you look in the acknowledgments of Ratliff’s publication you will find the ubiquitous Russ Hobbie among those thanked for their helpful suggestions.

Friday, August 21, 2009

The ECG Dance

In Chapter 7 of the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I describe the electrocardiogram. I always thought that the best way to teach the ECG was an online cardiac rhythm simulator. But now, thanks to a tip from my former student Debbie Janks, I have found an even better way to teach the ECG. Check out this video on youtube. I will have to try this myself next time I teach Biological Physics.

 Living Arrhythmias with John Grammer.
https://www.youtube.com/embed/deigcmtDV74

Friday, August 14, 2009

The Bell Curve

I was browsing through the 4th edition of Intermediate Physics for Medicine and Biology the other day (I do this sometimes; don’t ask why), and I noticed the footnote at the bottom of page 566 in Appendix H: The Binomial Probability Distribution, which states
See also A. Gawande, The bell curve. The New Yorker, December 6, 2004, pp. 82–91.
I thought to myself, “that must be one of the changes Russ Hobbie made when we were preparing the 4th edition, because I don’t remember ever reading the article.” Well, if Russ recommends it, then I want to read it, so I found the article on the web. It turns out to be a lovely, well-written piece about cystic fibrosis (CF), modern medicine, self-evaluation, and striving for excellence. The excerpt below is the one Russ probably had in mind when he added the citation of the article to our book. It describes a discussion between a teenage CF patient, Janelle, her physician Dr. Warwick, and the article’s author Atul Gawande, who is a surgeon and was observing Janelle’s interview as part of an effort to improve cystic fibrosis care. In the quote below, Janelle’s doctor is speaking.
“Let’s look at the numbers,” he said to me, ignoring Janelle. He went to a little blackboard he had on the wall. It appeared to be well used. “A person’s daily risk of getting a bad lung illness with CF is 0.5 per cent.” He wrote the number down. Janelle rolled her eyes. She began tapping her foot. “The daily risk of getting a bad lung illness with CF plus treatment is 0.05 per cent,” he went on, and he wrote that number down. “So when you experiment you’re looking at the difference between a 99.95-per-cent chance of staying well and a 99.5-per-cent chance of staying well. Seems hardly any difference, right? On any given day, you have basically a one-hundred-per-cent chance of being well. But”—he paused and took a step toward me—“it is a big difference.” He chalked out the calculations. “Sum it up over a year, and it is the difference between an eighty-three-per-cent chance of making it through 2004 without getting sick and only a sixteen-per-cent chance.
He turned to Janelle. “How do you stay well all your life? How do you become a geriatric patient?” he asked her. Her foot finally stopped tapping. “I can’t promise you anything. I can only tell you the odds.”
In this short speech was the core of Warwick’s world view. He believed that excellence came from seeing, on a daily basis, the difference between being 99.5-per-cent successful and being 99.95-per-cent successful. Many activities are like that, of course: catching fly balls, manufacturing microchips, delivering overnight packages. Medicine’s only distinction is that lives are lost in those slim margins.
The article describes how one CF center began measuring its own success against the top programs in the country, and their efforts to improve. Gawande concludes
The hardest question for anyone who takes responsibility for what he or she does is, What if I turn out to be average? If we took all the surgeons at my level of experience, compared our results, and found that I am one of the worst, the answer would be easy: I’d turn in my scalpel. But what if I were a C? Working as I do in a city that’s mobbed with surgeons, how could I justify putting patients under the knife? I could tell myself, Someone’s got to be average. If the bell curve is a fact, then so is the reality that most doctors are going to be average. There is no shame in being one of them, right?
Except, of course, there is. Somehow, what troubles people isn’t so much being average as settling for it. Everyone knows that averageness is, for most of us, our fate. And in certain matters—looks, money, tennis—we would do well to accept this. But in your surgeon, your child’s pediatrician, your police department, your local high school? When the stakes are our lives and the lives of our children, we expect averageness to be resisted. And so I push to make myself the best. If I’m not the best already, I believe wholeheartedly that I will be. And you expect that of me, too. Whatever the next round of numbers may say.

Friday, August 7, 2009

Technetium Shortage....Again

Readers of this blog (are there any?) may recall two earlier entries on December 14, 2007 and the May 23, 2008, when I discussed a shortage of technetium for medical imaging. It seems that this problem just won’t go away. According to a recent article in the New York Times, we are once again experiencing a global shortage of technetium, caused by the shutdown of nuclear reactors in Canada and the Netherlands. I fear that although the current shortage may be temporary, disruptions of the supply of technetium will reoccur with increasing frequency as nuclear power plants age. A reactor dedicated to technetium production in the United States would go a long way toward solving the problem, but would be expensive.

Russ Hobbie and I discussed technetium in the 4th edition of Intermediate Physics for Medicine and Biology. Technetium-99m—the key isotope of technetium for medical imaging—is a decay product of molybdenum-99, which in turn is a nuclear fragment that is produced during the fission of uranium. It is widely used in part because its 140 keV gamma emission and its 6 hour half life are particularly suited to nuclear medicine diagnostic procedures. 99mTc is often combined with other molecules to make radiopharmaceuticals, such as 99mTc-sestamibi and 99mTc-tetrofosmin, that can have very specific effects as tracers. For more about the discovery of technetium, see the March 13, 2009 entry of this blog.