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.”
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 100: 1162-1166.

Of course, 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 in 1938, 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 Rhode’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 Rhode’s book and enjoy the story (or listen to it here, the walk in the woods part starts at about 10 hours, 5 minutes and 42 seconds). Also, you can listen to Ruth Lwein Sime talk about Meitner's life and work here.

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)”
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, 80: 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 mechanism, 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)

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.

Friday, May 9, 2014

Celebrating the 60th Anniversary of the IEEE TBME

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. In fact, 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. 25: 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. 29: 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. 31: 274–285.

Stark, L. W. (1984). The pupil as a paradigm for neurological control systems. IEEE Trans. Biomed. Eng. 31: 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. 32: 136–140.

Geddes, L. A., and J. D. Bourland (1985). The strength-duration curve. IEEE Trans. Biomed. Eng. 32: 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. 33: 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. 33: 910–921. 

Pickard, W. F. (1988). A model for the acute electrosensitivity of cartilaginous fishes. IEEE Trans. Biomed. Eng. 35: 243–249. 

Purcell, C. J., G. Stroink, and B. M. Horacek (1988). Effect of torso boundaries on electrical potential and magnetic field of a dipole. IEEE Trans. Biomed. Eng. 35: 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. 37: 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. 39: 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. 39: 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. 41: 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. 41: 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. 42: 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. 42: 934–941. 

Roth, B. J. (1997). Electrical conductivity values used with the bidomain model of cardiac tissue. IEEE Trans. Biomed. Eng. 44: 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. 46: 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].


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.