Friday, July 4, 2014

Our Job is to Find Stupid and Get Rid of It

This week I have been on vacation, including a trip to Kansas City to see relatives and a visit to the Grand Canyon. So, I don’t have much time for updating this blog. My work on the 5th edition of Intermediate Physics for Medicine and Biology has slowed to a crawl, and I need to get back to it next week.

This week I will simply suggest you watch and listen to the inspiring Boston University 2014 commencement address by my friend Kevin Kit Parker.


My favorite quote from the address is the title of this blog entry. Parker is with the Harvard School of Engineering and Applied Sciences. Academically speaking, he and I are brothers; we share a common PhD advisor, John Wikswo of Vanderbilt University. Parker obtained his PhD about ten years after I received mine, and I met him when I was on the faculty at Vanderbilt for a few years in the late 1990s.

Parker is known both for his science, and for being a scientist/soldier. You can learn more about his experiences in an interview that aired on the TV show 60 Minutes.

Friday, June 27, 2014

Microscopes

The microscope is one of the most widely used instruments in science. Microscopy is a huge subject, and I am definitely not an expert. Russ Hobbie and I talk about the microscope only briefly in the 4th edition of Intermediate Physics for Medicine and Biology. In Chapter 14 (Atoms and Light) we give a series of homework problems about lenses. Problem 43 considers the case of an object placed just outside the focal point of a converging lens. The resulting image is real, inverted and magnified (a slide projector, for those of you old enough to remember such things). In Problem 44, the object is just inside the focal point of the lens. The image is virtual, upright, and magnified (a magnifying glass). Then in Problem 45 we put these two lenses together, first a slide projector casting an intermediate image, then a magnifying glass to view that image; a compound microscope. Our discussion is useful, but very simple.

Nowadays, microscopes are extremely complicated, and can do all sorts of wonderful things. Our simple example is nearly obsolete, because almost no one looks through the second lens (the eyepiece) to view the image anymore. Rather, the image produced by the first lens (the objective) is recorded digitally, and one looks at it on a computer screen. I could spend the rest of this blog entry describing the complexities of microscopes, but I want to go in another direction. Can a student build a simple yet modern microscope?

They can, and it makes a marvelous upper-level physics laboratory project. The proof is given by Jennifer Ross of the University of Massachusetts Amherst. In a preprint at her website, Ross describes a microscope project for undergraduates. The abstract reads:
Optics is an important subfield of physics required for instrument design and used in a variety of other disciplines, including materials science, physics, and life sciences such as developmental biology and cell biology. It is important to educate students from a variety of disciplines and backgrounds in the basics of optics in order to train the next generation of interdisciplinary researchers and instrumentalists who will push the boundaries of discovery. In this paper, we present an experimental system developed to teach students in the basics of geometric optics, including ray and wave optics. The students learn these concepts through designing, building, and testing a home-built light microscope made from component parts. We describe the experimental equipment and basic measurements students can perform to learn principles, technique, accuracy, and resolution of measurement. Students find the magnification and test the resolution of the microscope system they build. The system is open and versatile to allow advanced building projects, such as epi-fluorescence, total internal reflection fluorescence, and optical trapping. We have used this equipment in an optics course, an advanced laboratory course, and graduate-level training modules.
This fascinating paper then goes on to describe many aspects of microscope design.
The light source was a white light emitting diode (LED)… We chose inexpensive but small and powerful CMOS cameras to capture images with a USB link to a student’s laptop….The condenser designs of students are the most variable and interesting part of the microscope design. Students in prior years have used one, two, or three lenses to create evenly illuminated light on the sample plane…After creating the condenser, students next have to use an objective to create an image onto the CMOS camera chip.
The equipment is not terribly expensive compared to buying a microscope, but it’s not cheap: each microscope costs about $3000 to build, which means for a team of three students the cost is $1000 per person. But the leaning is tremendous, and Ross suggests that you can scavenge used parts to reduce the cost.

But perhaps even this student-built $3000 microscope is too complicated and expensive for you. Can we go simpler and cheaper? Yes! Consider “foldscope.” The website of foldscope’s inventors says (my italics)
We are a research team at PrakashLab at Stanford University, focused on democratizing science by developing scientific tools that can scale up to match problems in global health and science education. Here we describe Foldscope, a new approach for mass manufacturing of optical microscopes that are printed-and-folded from a single flat sheet of paper, akin to Origami….Although it costs less than a dollar in parts, it can provide over 2,000X magnification with sub-micron resolution (800 nm), weighs less than two nickels (8.8 g), is small enough to fit in a pocket (70 × 20 × 2 mm3), requires no external power, and can survive being dropped from a 3-story building or stepped on by a person. Its minimalistic, scalable design is inherently application-specific instead of general-purpose gearing towards applications in global health, field based citizen science and K12-science education.
Details are described in a preprint available at http://arxiv.org/abs/1403.1211. Also, listen to Manu Prakash give a TED talk about foldscope. The goal is to provide “a microscope for every child.” I think Prakash and his team means EVERY child (as in every single child in the whole wide world).

Friday, June 20, 2014

The Airy Disk

I hate to find errors in the 4th edition of Intermediate Physics for Medicine and Biology. When we do find any, Russ Hobbie and I let our readers know through an errata, published on the book’s website. Last week, I found another error, and it’s a particularly annoying one. First, let me tell you the error, and then I’ll fill in the backstory.

In the errata, you will now find this entry:
Page 338: In Chapter 12, Problem 10. The final equation, a Bessel function integral, should be
An integral relationship among Bessel functions.
Error found 6-10-14.
In the 4th edition, we left out the leading factor of “u” on the right-hand-side. Why does this bother me so much? In part, because Problem 10 is about a famous and important calculation. Chapter 12 is about imaging, and Problem 10 asks the reader to calculate the two-dimensional Fourier transform of the “top hat,” function equal to 1 for r less than a (a circular disk), and zero otherwise. This Fourier transform is, to within a constant factor, equal to J1(u)/u, where J1 is a Bessel function and u = ka, with k being the magnitude of the spatial frequency. This function is known as the “Airy pattern” or “Airy disk.” The picture below shows what the Airy disk looks like when plotted versus spatial frequencies kx and ky:

A plot of the Airy disk.
The Airy disk.

A picture of the square of this function is shown in Fig. 12.1 of IPMB. If you make a smaller, so the “top hat” is narrower, then in frequency space the Airy disk spreads out. Conversely, if you make a larger, so the “top hat” is wider, then in frequency space the Airy disk is more localized. The Bessel function oscillates, passing through zero many times. Qualitatively, J1(u)/u looks similar to the more familiar sinc function, sin(ka)/ka. (The sinc function appears in the Fourier transform of a rectangular “top hat” function).

The Airy disk plays a particularly important role in diffraction, a topic only marginally discussed in IPMB. Interestingly, diffraction isn’t important enough in our book even to make the index. We do mention it briefly in Chapter 13
One property of waves is that diffraction limits our ability to produce an image. Only objects larger than or approximately equal to the wavelength can be imaged effectively. This property is what limits light microscopes (using electromagnetic waves to form an image) to resolutions equal to about the wavelength of visible light, 500 nm.
We don’t talk at all about Fourier optics in IPMB. When light passes through an aperture, the image formed by Fraunhofer diffraction is the Fourier transform of the aperture function. So, for instance, when light passes through the objective lens of a microscope (or some other aperture in the optical path), the aperture function is the top hat function: all the light passes through at radii less than the radius of the lens, and no light passes through at larger radii. So the image formed by the lens of a point object (to the extent that the assumptions underlying Fraunhofer diffraction apply) is the Airy disk. Instead of a point image, you get a little blur.

Suppose you are trying to image two point objects. After diffraction, the image is two Airy disks. Can you resolve them as two separate objects? It depends on the extent of the overlap of the little blurs. Typically one uses the Rayleigh criterion to answer this question. If the two Airy disks are separated by at least the distance from the center of one Airy disk to its first zero, then the two objects are considered resolved. This is, admittedly, an arbitrary definition, but is entirely reasonable and provides a quantitative meaning to the vague term “resolved.” Thus, the imaging resolution of a microscope is determined by the zeros of the J1 Bessel function, which I find pretty neat. (I love Bessel functions).

So, you see, when I realized our homework problem had a typo and it meant the student would calculate the Airy disk incorrectly, my heart sunk. To any students who got fooled by this problem, I apologize. Mea culpa. It makes me all the more determined to keep errors out of the upcoming 5th edition, which Russ and I are working on feverishly.

On the lighter side, when I run into scientists I am not familiar with, I often look them up in Asimov’s Biographical Encyclopedia of Science and Technology. When I looked up George Biddell Airy (1801–1892), Astronomer Royal of the Greenwich Observatory, I was shocked. Asimov writes “he was a conceited, envious, small-minded man and ran the observatory like a petty tyrant.” Oh Myyy!

Friday, June 13, 2014

Physics Research & Education: The Complex Intersection of Biology and Physics

This morning, I am heading home after a productive week at a Gordon Research Conference about “Physics Research and Education: The Complex Intersection of Biology and Physics.” I wish I could tell you more about it, but Gordon Conferences have this policy…
To encourage open communication, each member of a Conference agrees that any information presented at a Gordon Research Conference, whether in a formal talk, poster session, or discussion, is a private communication from the individual making the contribution and is presented with the restriction that such information is not for public use….
So, there is little I can say, other than to point you to the meeting schedule published on the GRC website. I suspect that future blog entries will be influenced by what I learned this week, but I will only write about items that have also been published elsewhere.

 I can say a bit about Gordon Conferences in general. The GRC website states
The Gordon Research Conferences were initiated by Dr. Neil E. Gordon, of the Johns Hopkins University, who recognized in the late 1920s the difficulty in establishing good, direct communication between scientists, whether working in the same subject area or in interdisciplinary research. The Gordon Research Conferences promote discussions and the free exchange of ideas at the research frontiers of the biological, chemical and physical sciences. Scientists with common professional interests come together for a full week of intense discussion and examination of the most advanced aspects of their field. These Conferences provide a valuable means of disseminating information and ideas in a way that cannot be achieved through the usual channels of communication—publications and presentations at large scientific meetings.
Before this, the only Gordon Conference I ever attended was one at which I was the trailing spouse. My wife studied the interaction of lasers with tissue in graduate school, and she attended a Gordon Conference on that topic in the 1980s; I tagged along. I don’t remember that conference being as intense as this one, but maybe that’s because I’m getting older.

The conference was at Mount Holyoke College, a small liberal arts college in South Hadley, Massachusetts, about 90 minutes west of Boston. It is a lovely venue, and we were treated well. I hadn’t lived in a dormitory since college, but I managed to get used to it.

For those of you interested in education at the intersection of physics and biology—a topic of interest for readers of the 4th edition of Intermediate Physics for Medicine and Biology—I suggest you take a look at the recent special issue of the American Journal of Physics about “Research and Education at the Crossroads of Biology and Physics,” discussed in this blog before. In addition, see the website set up based on the “Conference on Introductory Physics for the Life Sciences,” held March 14–16, 2014 in Arlington, Virginia. I’ve also discussed the movement to improve introductory physics classes for students in the life sciences previously in this blog here, here, here, and here.

Now, I need to run so I can catch my plane….

Friday, June 6, 2014

Plant Physics

Perhaps the 4th edition of Intermediate Physics for Medicine and Biology should have a different title. It really should be Intermediate Physics for Medicine and Zoology. Russ Hobbie and I talk a lot about the physics of animals, but not much about plants. There is little botany in our book. This is not completely true. Homework Problem 34 in Chapter 1 (Mechanics) analyzes the ascent of sap in trees, and we briefly mention photosynthesis in Chapter 3 (Systems of Many Particles). I suppose our discussion of Robert Brown’s observation of the random motion of pollen particles counts as botany, but just barely. Chapter 8 (Biomagnetism) is surprisingly rich in plant examples, with both magnetotactic and biomagnetic signals from algae. But on the whole, our book talks about the physics of animals, and especially humans. I mean, really, who cares about plants?

Plant Physics, by Karl Niklas and Hans-Christof Spatz.
Plant Physics, by
Karl Niklas and Hans-Christof Spatz.
Guess what? Some people care very much about plants! Karl Niklas and Hanns-Christof Spatz have written a book titled Plant Physics. What is it about? In many ways, it is IPMB redone with only plant examples. Their preface states
This book has two interweaving themes—one that emphasizes plant biology and another that emphasizes physics. For this reason, we have called it Plant Physics. The basic thesis of our book is simple: plants cannot be fully understood without examining how physical forces and processes influence their growth, development, reproduction, and evolution….This book explores…many…insights that emerge when plants are studied with the aid of physics, mathematics, engineering, and chemistry. Much of this exploration dwells on the discipline known as solid mechanics because this has been the focus of much botanical research. However, Plant Physics is not a book about plant solid mechanics. It treats a wider range of phenomena that traditionally fall under the purview of physics, including fluid mechanics, electrophysiology, and optics. It also outlines the physics of physiological processes such as photosynthesis, phloem loading, and stomatal opening and closing.
The chapter titles in Plant Physics overlap with topics in IPMB, such as Chapter 4 (The Mechanical Behavior of Materials), Chapter 6 (Fluid Mechanics), and Chapter 7 (Plant Electrophysiology). I found the mathematical level of the book to be somewhat lower than IPMB, and probably closer to Denny’s Air and Water. (Interestingly, they did not cite Air and Water in their Section 2.3, Living in Water Versus Air, but they do cite another of Denny’s books, Biology and the Mechanics of the Wave-Swept Environment.) The differences between air and water plays a key role in plant life: “It is very possible that the colonization of land by plant life was propelled by the benefits of exchanging a blue and often turbid liquid for an essentially transparent mixture of gasses.” The book discusses diffusion, the Reynold’s number, chemical potential, Poiseuille flow, and light absorption. Chapter 3 is devoted to Plant Water Relations, and contains an example that serves as a model for how physics can play a role in biology. The opening and closing of stomata (“guard cells”) in leaves involves diffusion, osmotic pressure, feedback, mechanics, and optics. Fluid flow through both the xylem (transporting water from the roots to the leaves) and phloem (transporting photosynthetically produced molecules from the leaves to the rest of the plant) are discussed. Biomechanics plays a larger role in Plant Physics than in IPMB, and at the start of Chapter 4 the authors explain why.
The major premise of this book is that organisms cannot violate the fundamental laws of physics. A corollary to this premise is that organisms have evolved and adapted to mechanical forces in a manner consistent with the limits set by the mechanical properties of the materials out of which they are constructed…We see no better expression of these assertions that when we examine how the physical properties of different plant materials influence the mechanical behavior of plants.
Russ and I discuss Poisson’s ratio in a homework problem in Chapter 1. Niklas and Spatz give a nice example of how a large Poisson’s ratio can arise when a cylindrical cell has inextensible fibers in its cell wall that follow a spiral pattern. 
Values [of the Poisson’s ratio] can be very different [from isotropic materials] for composite biological materials such as most tissues, for which Poisson’s ratios greater than 1.0 can be found. A calculation presented in box 4.2 shows that in a sclerenchyma cell, in which practically inextensible cellulose microfibers provide the strengthening material in the cell wall, the Poisson’s ratio strongly depends on the microfibrillar angle; that is, the angle between fibers and the longitudinal axis of the cell.
Given my interest in bioelectric phenomena, I was especially curious about the chapter on Plant Electrophysiology (Chapter 7). The authors derive the Nernst-Planck equation, and the Goldman equation for the transmembrane potential. Interestingly, plants contain potassium and calcium ion channels, but no sodium channels. Many plants have cells that fire action potentials, but the role of the sodium channel for excitation is replaced by a calcium-dependent chloride channel. These are slowly propagating waves; Niklas and Spatz report conduction velocities of less than 0.1 m/s, compared to propagation in a large myelinated human axon, which can reach up to 100 m/s. Patch clamp recordings are more difficult in plant than in animal cells (plants have a cell wall in addition to a cell membrane). Particularly interesting to me were the gravisensitive currents in Lepidium sativum roots. The distribution of current is determined by the orientation of the root in a gravitational field.

Botanists need physics just as much as zoologists do. Plants are just one more path leading from physics to biology.

For those wanting to learn more, my colleague at Oakland University, Steffan Puwal, plans to offer a course in Plant Physics in the winter 2015 semester.

Friday, May 30, 2014

Pierre Auger and Lise Meitner

Last week in this blog, I discussed Auger electrons and their role in determining the radiation dose to biological tissue. This week, I would like to examine a bit of history behind the discovery of Auger electrons.

Auger electrons are named for Pierre Auger (1899–1993), a French physicist. Lars Persson discusses Auger’s life and work in a short biographical article (Acta Oncologica, Volume 35, Pages 785–787, 1996)
From the onset of his scientific work in 1922 Pierre Auger took an interest in the cloud chamber method discovered by Wilson and applied it to studying the photoelectric effect produced by x-rays on gas atoms. The Wilson method provided him with the most direct means of obtaining detailed information on the photoelectrons produced, since their trajectories could be followed when leaving the atom that had absorbed the quantum of radiation. He filled the chamber with hydrogen, which has a very low x-ray absorption coefficient, and a small proportion of highly absorbent and chemically neutral heavy gases, such as krypton and xenon. Auger observed some reabsorption in the gas, but most often found that the expected electron trajectory started from the positive ion itself. Numerous experiments enabled Auger to show that the phenomenon is frequent and amounts to non-radiactive transitions among the electrons of atoms ionized in depth. This phenomenon was named the auger effect, and the corresponding electrons auger electrons. His discovery was published in the French scientific journal Comptes Rendus as a note titled “On secondary beta-rays produced in a gas by x-rays” (1925; 180: 65–8). He was awarded several scientific prizes and was also a nominee for the Nobel Prize in physics which however, he never received. He was a member of the French Academy of Science. Pierre Auger was certainly one of the great men who created the 20th century in science.
Lise Meitner: A Life in Physics, by Ruth Lewin Sime, with Intermediate Physics for Medicine and Biology.
Lise Meitner:
A Life in Physics,
by Ruth Lewin Sime.
What is most interesting to me about the discovery of Auger electrons is that Auger may have been scooped by one of my favorite physicists, Lise Meitner (1878–1968). I didn’t think I would have the opportunity to discuss Meitner in a blog about physics in medicine and biology, and her name never appears in the 4th edition of Intermediate Physics for Medicine and Biology. But the discovery of Auger electrons gives me an excuse to tell you about her. In the book Lise Meitner: A Life in Physics, Ruth Lewin Sime writes about Meitner’s research on UX1 (now known to be the isotope thorium-234)
According to Meitner, the primary process was simply the emission of a decay electron from the nucleus. In UX1 she believed there was no nuclear gamma radiation at all. Instead the decay electron directly ejected a K shell electron, an L electron dropped into the vacancy, and the resultant Kα radiation was mostly reabsorbed to eject L, M, or N electrons from their orbits, all in the same atom. The possibility of multiple transitions without the emission of radiation had been discussed theoretically; Meitner was the first to observe and describe such radiationless transitions. Two years later, Pierre Auger detected the short heavy tracks of the ejected secondary electrons in a cloud chamber, and the effect was named for him. It has been suggested that the “Auger effect” might well have been the “Meitner effect” or at least the “Meitner-Auger effect” had she described it with greater fanfare, but in 1923 it was only part of a thirteen-page article whose main thrust was the beta spectrum of UX1 and the mechanism of its decay.
On the other hand, for an argument in support of Auger’s priority, see Duparc, O. H. (2009) “Pierre Auger – Lise Meitner: Comparative Contributions to the Auger Effect,” International Journal of Materials Research Volume 100, Pages 1162–1166.

The Making of the Atomic Bomb, by Richard Rhodes, superimposed on Intermediate Physics for Medicine and Biology.
The Making of the Atomic Bomb,
by Richard Rhodes.
Meitner is best know for her work on nuclear fission, described so eloquently by Richard Rhodes in his masterpiece The Making of the Atomic Bomb. Meitner was an Austrian physicist of Jewish descent working in Germany with Otto Hahn. After the Anschluss, Hitler planned to expel Jewish scientists from their academic positions, but also forbade their emigration. With the help of her Dutch colleague Dirk Coster (who is mentioned in IPMB because of Coster-Kronig transitions), she slipped out of Berlin in July 1938. Rhodes writes
Meitner left with Coster by train on Saturday morning. Nine years later she remembered the grim passage as if she had traveled alone: “I took a train for Holland on the pretext that I wanted to spend a week’s vacation. At the Dutch border, I got the scare of my life when a Nazi military patrol of five men going through the coaches picked up my Austrian passport, which had expired long ago. I got so frightened, my heart almost stopped beating. I knew that the Nazis had just declared open season on Jews, that the hunt was on. For ten minutes I sat there and waited, ten minutes that seemed like so many hours. Then one of the Nazi officials returned and handed me back the passport without a word. Two minutes later I descended on Dutch territory, where I was met by some of my Holland colleagues.”
Even better reading is Rhodes’s description of Meitner’s fateful December 1938 walk in the woods with her nephew Otto Frisch, during which they sat down on a log, worked out the mechanism of nuclear fission, and correctly interpreted Hahn’s experimental data. Go buy his book and enjoy the story. Also, you can listen to Ruth Lewin Sime talk about Meitner’s life and work here.

Listen to Ruth Lwein talk about Lise Meitner’s life.

Friday, May 23, 2014

The Amazing World of Auger Electrons

When analyzing how ionizing radiation interacts with biological tissue, one important issue is the role of Auger electrons. In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I introduce Auger electrons in Chapter 15 (Interaction of Photons and Charged Particles with Matter). An X-ray or charged particle ionizes an atom, leaving a hole in the electron shell.
The hole in the shell can be filled by two competing processes: a radiative transition, in which a photon is emitted as an electron falls into the hole from a higher level, or a nonradiative or radiationless transition, such as the emission of an Auger electron from a higher level as a second electron falls from a higher level to fill the hole.
We consider Auger electrons again in Chapter 17 (Nuclear Physics and Nuclear Medicine). In some cases, a cascade of relatively low energy electrons are produced by one ionizing event.
The Auger cascade means that several of these electrons are emitted per transition. If a radionuclide is in a compound that is bound to DNA, the effect of several electrons released in the same place is to cause as much damage per unit dose as high-LET [linear energy transfer] radiation….Many electrons (up to 25) can be emitted for one nuclear transformation, depending on the decay scheme [Howell (1992)]. The electron energies vary from a few eV to a few tens of keV. Corresponding electron ranges are from less than 1 nm to 15 μm. The diameter of the DNA double helix is about 2 nm…When it [the radionuclide emitting Auger electrons] is bound to the DNA, survival curves are much steeper, as with the α particles in Fig. 15.32 (RBE [relative biological effectiveness] ≈ 8)
The Amazing World of Auger Electrons, by  Amin Kassis (International Journal of Radiation Biology, 80: 789-803), superimposed on the cover of Intermediate Physics for Medicine and Biology.
“The Amazing World
of Auger Electrons.”
In IPMB, Russ and I cite a paper by Amin Kassis with the wonderful title “The Amazing World of Auger Electrons” (International Journal of Radiation Biology, Volume 80, Pages 789–803). Kassis begins
In 1925, a 26-year-old French physicist named Pierre Victor Auger published a paper describing a new phenomenon that later became known as the Auger effect (Auger 1925). He reported that the irradiation of a cloud chamber with low-energy, X-ray photons results in the production of multiple electron tracts and concluded that this event is a consequence of the ejection of inner-shell electrons from the irradiated atoms, the creation of primary electron vacancies within these atoms, a complex series of vacancy cascades composed of both radiative and nonradiative transitions, and the ejection of very low-energy electrons from these atoms. In later studies, it was recognized that such low-energy electrons are also ejected by many radionuclides that decay by electron capture (EC) and/or internal conversion (IC). Both of these processes introduce primary vacancies in the inner electronic shells of the daughter atoms which are rapidly filled up by a cascade of electron transitions that move the vacancy towards the outermost shell. Each inner-shell electron transition results in the emission of either a characteristic atomic X-ray photon or low-energy and short-range monoenergetic electrons (collectively known as Auger electrons, in honor of their discoverer).
Typically an atom undergoing EC and/or IC emits several electrons with energies ranging from a few eV to approximately 100 keV. Consequently, the range of Auger electrons in water is from a fraction of a nanometer to several hundreds of micrometers (table 1). The ejection of these electrons leaves the decaying atoms transiently with a high positive charge and leads to the deposition of highly localized energy around the decay site. The dissipation of the potential energy associated with the high positive charge and its neutralization may, in principle, also act concomitantly and be responsible for any observed biological effects. Finally, it is important to note that unlike energetic electrons, whose linear energy transfer (LET) is low (~0.2 keV/mm) along most of their rather long linear path (up to one cm in tissue), i.e. ionizations occur sparingly, the LET of Auger electrons rises dramatically to ~26 keV/mm (figure 1) especially at very low energies (35–550 eV) (Cole 1969) with the ionizations clustered within several cubic nanometers around the point of decay. From a radiobiological prospective, it is important to recall that the biological functions of mammalian cells depend on both the genomic sequences of double- stranded DNA and the proteins that form the nucleoprotein complex, i.e. chromatin, and to note that the organization of this polymer involves many structural level compactions (nucleosome, 30-nm chromatin fiber, chromonema fiber, etc.) [see Fig. 16.33 in IPMB] whose dimensions are all within the range of these high-LET (8–26 keV/mm), low-energy low-energy (less than 1.6 keV), short-range (less than 130 nm) electrons.
An example of an isotope that emits a cascade of Auger electrons is iodine-125. It has a half-life of 59 days, and decays to an excited state of tellurium-125. The atom deexcites by various mechanisms, including up to 21 Auger electrons with energies of 50 to 500 eV each. Kassis says
Among all the radionuclides that decay by EC and/or IC, the Auger electron emitter investigated most extensively is iodine-125. Because these processes lead to the emission of electrons with very low energies, early studies examined the radiotoxicity of iodine-125 in mammalian cells when the radioelement was incorporated into nuclear DNA consequent to in vitro incubations of mammalian cells with the thymidine analog 5-[125I]iodo-2’-deoxyuridine (125IdUrd). These studies demonstrated that the decay of DNA-incorporated 125I is highly toxic to mammalian cells.
I find it useful to compare 125I with 131I, another iodine radioisotope used in nuclear medicine. 131I undergoes beta decay, followed by emission of a gamma ray. Both the high energy electron from beta decay (up to 606 keV) and the gamma ray (364 keV) can travel millimeters in tissue, passing through many cells. In contrast, 125I releases its cascade of Auger electrons, resulting in extensive damage over a very small distance.

Civil War buffs might compare these two isotopes to the artillery ammunition of the 1860s. 131I is like a cannon firing shot (solid cannon balls), whereas 125I is like firing canister. If you are trying to take out an enemy battery 1000 yards away, you need shot. But if you are trying to repulse an enemy infantry charge that is only 10 yards away, you use canister or, better, double canister. 131I is shot, and 125I is double canister.

Friday, May 16, 2014

Paul Callaghan (1947-2012)

Principles of Nuclear Magnetic Resonance Microscopy, by Pual Callaghan, superimposed on Intermediate Physics for Medicine and Biology.
Principles of Nuclear
Magnetic Resonance Microscopy,
by Pual Callaghan.
Russ Hobbie and I are hard at work on the 5th edition of Intermediate Physics for Medicine and Biology, which has me browsing through many books—some new and some old classics—looking for appropriate texts to cite. The one I’m looking at now is Paul Callaghan’s Principles of Nuclear Magnetic Resonance Microscopy (Oxford University Press, 1991). Callaghan was the PhD mentor of my good friend and Oakland University colleague Yang Xia. You probably won’t be surprised to know that, like Callaghan, Xia is a MRI microscopy expert. He uses the technique to study the ultrastructure of cartilage at a resolution of tens of microns. Xia assigns Callaghan’s book when he teaches Oakland’s graduate MRI class.

Callaghan gives a brief history of MRI on the first page of his book.
Until the discovery of X-rays by Roentgen in 1895 our ability to view the spatial organization of matter depended on the use of visible light with our eyes being used as primary detectors. Unaided, the human eye is a remarkable instrument, capable of resolving separations of 0.1 mm on an object placed at the near point of vision and, with bifocal vision, obtaining a depth resolution of around 0.3 mm. However, because of the strong absorption and reflection of light by most solid materials, our vision is restricted to inspecting the appearance of surfaces. “X-ray vision” gave us the capacity, for the first time, to see inside intact biological, mineral, and synthetic materials and observe structural features.

The early X-ray photographs gave a planar representation of absorption arising from elements right across the object. In 1972 the first X-ray CT scanner was developed with reconstructive tomography being used to produce a two-dimensional absorption image from a thin axial layer.1 The mathematical methods used in such image reconstruction were originally employed in radio astronomy by Bracewell2 in 1956 and later developed for optical and X-ray applications by Cormack3 in 1963. A key element in the growth of tomographic techniques has been the availability of high speed digital computers. These machines have permitted not only the rapid computation of the image from primary data but have also made possible a wide variety of subsequent display and processing operations. The principles of reconstructive tomography have been applied widely in the use of other radiations. In 1973, Lauterbur4 reported the first reconstruction of a proton spin density map using nuclear magnetic resonance (NMR), and in the same year Mansfield and Grannell5 independently demonstrated the Fourier relationship between the spin density and the NMR signal acquired in the presence of a magnetic field gradient. Since that time the field has advanced rapidly to the point where magnetic resonance imaging (MRI) is now a routine, if expensive, complement to X-ray tomography in many major hospitals. Like X-ray tomography, conventional MRI has a spatial resolution coarser than that of the unaided human eye with volume elements of order (1 mm)3 or larger. Unlike X-ray CT however, where resolution is limited by the beam collimation, MRI can in principle achieve a resolution considerably finer than 0.1 mm and, where the resolved volume elements are smaller than (0.1 mm)3, this method of imaging may be termed microscopic.

1. Hounsfield, G. N. (1973). British Patent No. 1283915 (1972) and Br. J. Radiol. 46, 1016.

2. Bracewell, R. N. (1956). Austr. J. Phys. 9, 109–217.

3. Cormack, A. M. (1963). J. Appl. Phys. 34, 2722–7.

4. Lauterbur, P. C. (1973). Nature 242, 190.

5. Mansfield, P. and Grannell, P. K. (1973). J. Phys. C 6, L422.
Callaghan was an excellent teacher, and he prepared a series of videos about MRI. You can watch them for free here. They really are “must see” videos for people wanting to understand nuclear magnetic resonance. He was a professor at Massey University in Wellington, New Zealand. In 2011 he was named New Zealander of the Year, and you can hear him talk about scientific innovation in New Zealand here.

Callaghan died about two years ago. You can see his obituary here, here and here. Finally, here you can listen to an audio recording of Yang Xia speaking about his mentor at the Professor Sir Paul Callaghan Symposium in February 2013.

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Friday, May 9, 2014

Celebrating the 60th Anniversary of the IEEE TBME

The cover of the journal IEEE Transactions on Biomedical Engineering.
IEEE Transactions on
Biomedical Engineering.
One journal that I have published in several times is the IEEE Transactions on Biomedical Engineering. The May issue of IEEE TBME celebrates the journal’s 60th anniversary. Bin He, editor-in-chief, writes in his introductory editorial
THE IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING (TBME) is celebrating 60 years of publishing biomedical engineering advances. TBME was one of the first journals devoted to biomedical engineering. Thanks to IEEE, all of the TBME papers since January 1964 have been archived and are available to the public. In this special issue, celebrating TBME’s 60th anniversary, we have invited 20 leading groups in biomedical engineering research to contribute review articles. Each article reviews state of the art and trends in an area of biomedical engineering research in which the authors have made important original contributions. Due to limited space, it is not our intention to cover all areas of biomedical engineering research in this special issue, but instead to provide coverage of major subfields within the discipline of biomedical engineering, including biomedical imaging, neuroengineering, cardiovascular engineering, cellular and tissue engineering, biomedical sensors and instrumentation, biomedical signal processing, medical robotics, bioinformatics, and computational biology. These review articles are witness to the development of the field of biomedical engineering, and also reflect the role that TBME has played in advancing the field of biomedical engineering over the past 60 years…
These comprehensive and timely reviews reflect the breadth and depth of biomedical engineering and its impact to engineering, biology, medicine, and the larger society. These reviews aim to serve the readers in gaining insights and an understanding of particular areas in biomedical engineering. Many articles also share perspectives from the authors on future trends in the field. While the intention of this special issue was not to cover all research programs in biomedical engineering, these 20 articles represent a collection of state-of-the-art reviews that highlight exciting and significant research in the field of biomedical engineering and will serve TBME readers and the biomedical engineering community in years to come.
Biomedical Engineering can be thought of as an applied version of medical and biological physics, and many of the topics Russ Hobbie and I discuss in the 4th edition of Intermediate Physics for Medicine and Biology are important to biomedical engineers. We cite nineteen IEEE TBME papers in IPMB:
Tucker, R. D., and O. H. Schmitt (1978) “Tests for Human Perception of 60 Hz Moderate Strength Magnetic Fields,” IEEE Trans. Biomed. Eng. Volume 25, Pages 509–518.

Wiley, J. D., and J. G. Webster (1982) “Analysis and Control of the Current Distribution under Circular Dispersive Electrodes,” IEEE Trans. Biomed. Eng. Volume 29, Pages 381–385. 

Cohen, D., I. Nemoto, L. Kaufman, and S. Arai (1984) “Ferrimagnetic Particles in the Lung Part II: The Relaxation Process,” IEEE Trans. Biomed. Eng. Volume 31, Pages 274–285.

Stark, L. W. (1984) “The Pupil as a Paradigm for Neurological Control Systems,” IEEE Trans. Biomed. Eng. Volume 31, Pages 919–924. 

Barach, J. P., B. J. Roth, and J. P. Wikswo (1985) “Magnetic Measurements of Action Currents in a Single Nerve Axon: A Core Conductor Model,” IEEE Trans. Biomed. Eng. Volume 32, Pages 136–140.

Geddes, L. A., and J. D. Bourland (1985) “The Strength-Duration Curve,” IEEE Trans. Biomed. Eng. Volume 32, Pages 458–459. 

Stanley, P. C., T. C. Pilkington, and M. N. Morrow (1986) “The Effects of Thoracic Inhomogeneities on the Relationship Between Epicardial and Torso Potentials,” IEEE Trans. Biomed. Eng. Volume 33, Pages 273–284. 
Gielen, F. L. H., B. J. Roth and J. P. Wikswo, Jr. (1986) “Capabilities of a Toroid-Amplifier System for Magnetic Measurements of Current in Biological Tissue,” IEEE Trans. Biomed. Eng. Volume 33, Pages 910–921. 

Pickard, W. F. (1988) “A Model for the Acute Electrosensitivity of Cartilaginous Fishes,” IEEE Trans. Biomed. Eng. Volume 35, Pages 243–249. 

Purcell, C. J., G. Stroink, and B. M. Horacek (1988) “Effect of Torso Boundaries on Electrical Potential and Magnetic Field of a Eipole,” IEEE Trans. Biomed. Eng. Volume 35, Pages 671–678.

Trayanova, N., C. S. Henriquez, and R. Plonsey (1990) “Limitations of Approximate Solutions for Computing Extracellular Potential of Single Fibers and Bundle Equivalents,” IEEE Trans. Biomed. Eng. Volume 37, Pages 22–35.

Voorhees, C. R., W. D. Voorhees III, L. A. Geddes, J. D. Bourland, and M. Hinds (1992) “The Chronaxie for Myocardium and Motor Nerve in the Dog with Surface Chest Electrodes,” IEEE Trans. Biomed. Eng. Volume 39, Pages 624–628.

Tan, G. A., F. Brauer, G. Stroink, and C. J. Purcell (1992) “The Effect of Measurement Conditions on MCG Inverse Solutions,” IEEE Trans. Biomed. Eng. Volume 39, Pages 921–927.

Roth, B. J. and J. P. Wikswo, Jr. (1994) “Electrical Stimulation of Cardiac Tissue: A Bidomain Model with Active Membrane Properties,” IEEE Trans. Biomed. Eng. Volume 41, Pages 232–240.

Tai, C., and D. Jiang (1994) “Selective Stimulation of Smaller Fibers in a Compound Nerve Trunk with Single Cathode by Rectangular Current Pulses,” IEEE Trans. Biomed. Eng. Volume 41, Pages 286–291.

Kane, B. J., C. W. Storment, S. W. Crowder, D. L. Tanelian, and G. T. A. Kovacs (1995) “Force-Sensing Microprobe for Precise Stimulation of Mechanoreceptive Tissues,” IEEE Trans. Biomed. Eng. Volume 42, Pages 745–750. 
Esselle, K. P., and M. A. Stuchly (1995) “Cylindrical Tissue Model for Magnetic Field Stimulation of Neurons: Effects of Coil Geometry,” IEEE Trans. Biomed. Eng. Volume 42, Pages 934–941. 

Roth, B. J. (1997) “Electrical Conductivity Values Used with the Bidomain Model of Cardiac Tissue,” IEEE Trans. Biomed. Eng. Volume 44, Pages 326–328.

Roth, B. J., and M. C. Woods (1999) “The Magnetic Field Associated with a Plane Wave Front Propagating through Cardiac Tissue,” IEEE Trans. Biomed. Eng. Volume 46, Pages 1288–1292.
One endearing feature of the IEEE TBME is that at the end of an article they publish a picture and short bio of each author. Over the years, my goal has been to publish my entire CV, piece by little piece, in these short bios. Below is the picture and bio from my very first published paper, which appeared in IEEE TBME [Barach, Roth, and Wikswo (1985), cited above].

Short bio of Brad Roth, published in the IEEE Transactions on Biomedical Engineering.

Friday, May 2, 2014

Research and Education at the Crossroads of Biology and Physics

The May issue of the American Journal of Physics (my favorite journal) is a “theme issue” devoted to Research and Education at the Crossroads of Biology and Physics. In their introductory editorial, guest editors Mel Sabella and Matthew Lang outline their goals, which are similar to the objectives Russ Hobbie and I have for the 4th edition of Intermediate Physics for Medicine and Biology.
…there is often a disconnect between biology and physics. This disconnect often manifests itself in high school and college physics instruction as our students rarely come to understand how physics influences biology and how biology influences physics. In recent years, both biologists and physicists have begun to recognize the importance of cultivating stronger connections in these fields, leading to instructional innovations. One call to action comes from the National Research Council’s report, BIO2010, which stresses the importance of quantitative and computational training for future biologists and cites that sufficient expertise in physics is crucial to addressing complex issues in the life sciences. In addition, physicists who are now exploring biological contexts in instruction need the expertise of biologists. It is clear that biologists and physicists both have a great deal to offer each other and need to develop interdisciplinary workspaces…

This theme issue on the intersection of biology and physics includes papers on new advances in the fields of biological physics, new advances in the teaching of biological physics, and new advances in education research that inform and guide instruction. By presenting these strands in parallel, in a single issue, we hope to support the reader in making connections, not only at the intersection of biology and physics but also at the intersection of research, education, and education research. Understanding these connections puts us, as researchers and physics educators, in a better position to understand the central questions we face…

The infusion of Biology into Physics and Physics into Biology provides exciting new avenues of study that can inspire and motivate students, educators, and researchers at all levels. The papers in this issue are, in many ways, a call to biologists and physicists to explore this intersection, learn about the challenges and obstacles, and become excited about new areas of physics and physics education. We invite you to read through these articles, reflect, and discuss this complex intersection, and then continue the conversation at the June 2014 Gordon Research Conference titled, “Physics Research and Education: The Complex Intersection of Biology and Physics.”
And guess who has an article in this special issue? Yup, Russ and I have a paper titled “A Collection of Homework Problems About the Application of Electricity and Magnetism to Medicine and Biology.”
This article contains a collection of homework problems to help students learn how concepts from electricity and magnetism can be applied to topics in medicine and biology. The problems are at a level typical of an undergraduate electricity and magnetism class, covering topics such as nerve electrophysiology, transcranial magnetic stimulation, and magnetic resonance imaging. The goal of these problems is to train biology and medical students to use quantitative methods, and also to introduce physics and engineering students to biological phenomena.
Regular readers of this blog know that a “hobby” of mine (pun intended, Russ) is to write new homework problems to go along with our book. Some of the problems in our American Journal of Physics paper debuted in this blog. I believe that a well-crafted collection of homework problems is essential for learning biological and medical physics (remember, for them to be useful you have to do your homework). I hope you will find the problems we present in our paper to be “well-crafted”. We certainly had fun writing them. My biggest concern with our AJP paper is that the problems may be too difficult for an introductory class. The “I” in IPMB stands for “intermediate”, not “introductory”. However, most of the AJP theme issue is about the introductory physics class. Oh well; one needs to learn biological and medical physics at many levels, and the intermediate level is our specialty. If only our premed students would reach the intermediate level (sigh)….

Russ and I are hard at work on the 5th edition of our book, where many of the problems from our paper, along with additional new ones, will appear (as they say, You Ain’t Seen Nothing Yet!).

Anyone interested in teaching biological and medical physics should have a look at this AJP theme issue. And regarding that Gordon Research Conference that Sabella and Lang mention, I’m registered and have purchased my airline tickets! It should be fun. If you are interested in attending, the registration deadline is May 11 (register here). You better act fast.