Friday, February 24, 2017

Benefits and Barriers of Accommodating Intraocular Lenses

In Chapter 14 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss vision. In particular, we analyze the refraction of light by the lens of the eye, and examine different disorders such as hyperopia, and myopia. We then write
This ability of the lens to change shape and provide additional converging power is called accommodation…. As we age, the accommodation of the eye decreases... A normal viewing distance of 25 cm or less requires 4 diopters or more of accommodation... This limit is usually reached in the early 40s. To make up for the lack of accommodation, one can place a converging lens in front of the eye when viewing nearby objects (reading glasses).
When a patient has a cataract, their lens becomes cloudy. A common surgical procedure is to remove the opaque lens and replace it with an artificial intraocular lens. A conventional IOL is designed to supply the correct power to provide clear distance vision, but it cannot accommodate. Reading glasses provide one option for close vision, but many patients find them to be an inconvenient nuisance.

Researchers are now racing to create accommodating IOLs. A recent review by Jay Pepose, Joshua Burke, and Mujtaba Qazi discusses the “Benefits and Barriers of Accommodating Intraocular Lenses” (Current Opinion in Ophthalmology, Volume 28, Pages 3–8, 2017).
Presbyopia [the loss of accommodation] and cataract development are changes that ubiquitously affect the aging population. Considerable effort has been made in the development of intraocular lenses (IOLs) that allow correction of presbyopia postoperatively. The purpose of this review is to examine the benefits and barriers of accommodating IOLs, with a focus on emerging technologies.
Apparently the current accommodating intraocular lenses don’t function by changing their focal length, but rather by being pushed forward when the eye muscles responsible for accommodation contract. They only provide about 1 diopter of accommodation, which is not enough to avoid reading glasses. The review concludes
Such limitations [of the presently available accommodating IOLs] may be circumvented in the future by accommodative design strategies that rely more on shape-related changes in the surfaces of the IOLs or in refractive index than by forward translation alone. Fibrosis and contraction of the capsular bag, which can alter the position of the IOL optic or the performance of an accommodating IOL represent other challenges, and at least one accommodating IOL … has been designed for implantation in the ciliary sulcus. Approval of accommodating IOLs capable of delivering three or more diopters of accommodation would allow a full range of intermediate and near vision without the compromise of photic phenomenon or loss of contrast inherent to other optical strategies, and perhaps also allow refractive targeting that could minimize hyperopic surprises by taking advantage of this expanded amplitude of accommodation.
Some “accommodating” IOLs are multifocal, providing two focal lengths and therefore two images simultaneously, one for distance vision and one for reading. The brain then sorts out the mess. Apparently this is not as difficult as is sounds.

I predict that accommodating intraocular lenses will soon become very sophisticated. Cataract surgery is performed on millions of people each year; it is common in the elderly population, which is growing dramatically as baby boomers age; in principle the problem is not complex, you just need to make a lens that can adjust its focal length by about ten percent; compared to other medical devices like pacemakers and defibrillators, accommodating IOLs should be cheap; and new nanotechnologies plus knowledge gained from the miniaturization of other medical devices may pave the way to rapid advances. Accommodating intraocular lenses may soon become an example of how to successfully apply physics to solve a problem in medicine.

Friday, February 17, 2017

Sir Peter Mansfield (1933-2017)

MRI pioneer Peter Mansfield died last week. Russ Hobbie and I mention Mansfield in Chapter 18 of Intermediate Physics for Medicine and Biology
Many more techniques are available for imaging with magnetic resonance than for x-ray computed tomography. They are described by Brown et al. (1994), by Cho et al. (1993), by Vlaardingerbroek and den Boer (2004), and by Liang and Lauterbur (2000). One of these authors, Paul C. Lauterbur, shared with Sir Peter Mansfield the 2003 Nobel Prize in physiology or medicine for the invention of magnetic resonance imaging.
Mansfield made many contributions to the development of MRI, including the invention of echo-planar imaging. Russ and I write
Echo-planar imaging (EPI) eliminates the π pulses [normally used to rotate the spins in the x-y plane to form a spin echo]. It requires a magnet with a very uniform magnetic field, so that T2 [the transverse relaxation time, that is determined in part by dephasing of the spins in the x-y plane] (in the absence of a gradient) is only slightly greater than T2* [the experimentally observed transverse relaxation time]. The gradient fields are larger, and the gradient pulse durations shorter, than in conventional imaging. The goal is to complete all the k-space [all the points kx-ky in the spatial frequency domain] measurements in a time comparable to T2*. In EPI the echoes are not created using π pulses. Instead, they are created by dephasing the spins at different positions along the x axis using a Gx gradient, and then reversing that gradient to rephrase the spins, as shown in Fig. 18.32.
A magnetic resonance imaging pulse sequence for echo planar imaging, from Intermediate Physics for Medicine and Biology.
A MRI pulse sequence for echo planar imaging,
from Intermediate Physics for Medicine and Biology.

Mansfield tells about his first presentation on echo-planar imaging in his autobiography, The Long Road to Stockholm.
It was during the course of 1976 that Raymond Andrew convened a meeting in Nottingham of interested people in imaging…Most attendees brought us up to date with their images and gave us short talks on the goals that they were pursuing. Although my group had made considerable headway in a whole range of topics, I chose to speak about an entirely new imaging method that I had worked out theoretically but for which I had really no experimental results. The technique was called echo planar imaging (EPI), a condensation of planar imaging using spin echoes. I spoke for something like half an hour, talking in great detail, and at the end of the talk the audience seemed to be left in stunned silence. There were no questions, there was no discussion at all, and it was almost as though I had never spoken. In fact I had given a detailed talk about how one could produce very rapid images in a typically one shot process lasting, conservatively, for something like 40 or 50 milliseconds.
You can learn more about Mansfield in obituaries in the New York Times, in The Scientist, and from the BBC. Also, the Nobel Prize website has much information including a biography and his Nobel Prize address. Below, watch and listen to Mansfield talk about MRI.

Friday, February 10, 2017

Good, Fast, Cheap: Pick Any Two

When I worked at the National Institutes of Health, one of my coworkers had a sign in his office that read “Good, Fast, Cheap: Pick Any Two.” A recent video about “Building tomorrow's MRI--faster, smaller, and cheaper” reminded me of that saying. The video is part of a series called Science Happens! by Carl Zimmer.

Russ Hobbie and I describe magnetic resonance imaging in Chapter 18 of Intermediate Physics for Medicine and Biology. However, we don’t discuss the possibilities related to low-field MRI. The Science Happens! website says
Matthew Rosen and his colleagues at the Martinos Center for Biomedical Imaging in Boston want liberate the MRI. They’re hacking a new kind of scanner that’s fast, small, and cheap. Using clever algorithms, they can use a weak magnetic field to get good images of our brains and other organs. Someday, people may not have to go to hospital for an MRI. The scanners may show up in sports arenas, battlefields, and even the backs of ambulances.
A longer, more technical video of Rosen describing his work is given below.

For more details, see Rosen’s open access article “Low-Cost High-Performance MRI” (Scientific Reports, 5:15177, 2015).
Magnetic Resonance Imaging (MRI) is unparalleled in its ability to visualize anatomical structure and function non-invasively with high spatial and temporal resolution. Yet to overcome the low sensitivity inherent in inductive detection of weakly polarized nuclear spins, the vast majority of clinical MRI scanners employ superconducting magnets producing very high magnetic fields. Commonly found at 1.5–3 tesla (T), these powerful magnets are massive and have very strict infrastructure demands that preclude operation in many environments. MRI scanners are costly to purchase, site, and maintain, with the purchase price approaching $1 M per tesla (T) of magnetic field. We present here a remarkably simple, non-cryogenic approach to high-performance human MRI at ultra-low magnetic field, whereby modern under-sampling strategies are combined with fully-refocused dynamic spin control using steady-state free precession techniques. At 6.5 mT (more than 450 times lower than clinical MRI scanners) we demonstrate (2.5 × 3.5 × 8.5) mm3 imaging resolution in the living human brain using a simple, open-geometry electromagnet, with 3D image acquisition over the entire brain in 6 minutes. We contend that these practical ultra-low magnetic field implementations of MRI (less than 10 mT) will complement traditional MRI, providing clinically relevant images and setting new standards for affordable (less than $50,000) and robust portable devices.
$50,000 is expensive by Manu Prakash's standards, but for an MRI device $50k is darn cheap! Recalling my friend’s motto, I think that Rosen has picked Fast and Cheap, but he’s gotten Pretty Good too, which is not a bad trade-off (all of engineering is trade-offs). If you want Super Good, spend the million bucks.

Finally, Rosen isn’t the only one interested in reinventing magnetic resonance imaging. Michael Garwood at Russ’s own University of Minnesota is also working on smaller, lighter, cheaper MRI.

Let the race begin. Humanity will be the winner.


Friday, February 3, 2017

Alan Perelson wins the 2017 Max Delbruck Prize in Biological Physics

Alan Perelson, of Los Alamos National Laboratory, has been named the winner of the 2017 Max Delbruck Prize in Biological Physics by the American Physical Society. His award was “for profound contributions to theoretical immunology, which bring insight and save lives.”

One skill Russ Hobbie and I try to develop in students using Intermediate Physics for Medicine and Biology is the ability to translate words into mathematics. Below I present a new homework problem based on one of Perelson’s most highly cited papers (Perelson et al., 1996, Science, 271:1582–1586), which provides practice in this important technique. This exercise asks the student to make a mathematical model of the immune system that explains how T-cells—a type of white blood cell—respond to HIV infection.
Section 10.8

Problem 37 1/2. A model of HIV infection includes the concentration of uninfected T-cells, T, the concentration of infected T-cells, T*, and the concentration of virions, V.

(a) Write a pair of coupled differential equations for T* and V based on the following assumptions
  • If no virions are present, the immune system removes infected T-cells with rate δ,
  • If no infected T-cells are present, the immune system removes virions with rate c
  • Infected T-cells are produced at a rate proportional to the product of the concentrations of uninfected T-cells and virions; let the constant of proportionality be k
  • Virions are produced at a rate proportional to the concentration of infected T-cells with a constant of proportionality , where N is the number of virions per infected T-cell. 
(b) In steady state, determine the concentration of uninfected T-cells.
One of Perelson’s coauthors on the 1996 paper was David Ho. Yes, the David Ho who was Time Magazine’s Man of the Year in 1996.

For those who prefer video, watch Perelson discuss immunology for physicists.