Frontiers in Quantitative Imaging for Cancer Detection and Treatment - 2009 AIP Industrial Physics Forum

Now It's Time to Say Goodbye...

2009-08-03T09:13:29Z

At meetings end, my brain is jam packed with medical physics and lots of wonderful new information. The meeting was nothing if not educational, and notably collaborative as well. Both organizations played active, supportive roles in the sessions and invited a tremendous group of speakers. Representatives from so many different disciplines commented on how excited they were to be talking to members of different fields and sub-fields. For a first time joint meeting it came together brilliantly.

Although there were many talks that I couldn't cover, I did want to make quick note of one thing I didn't have time to go into detail about.

A group of talks on moving tumors showed some of the most cutting edge and most crucial advances presented at the meeting. In all types of cancer therapy, but especially proton therapy, knowing the location of a tumor is essential to efficiently delivering a dose of radiation or particles. Tumors can shift and move over days, as the patient changes position, or in the case of lung cancer every time the patient breaths. There are different ways to target moving tumors: you can follow the tumor with the beam, turn the beam on and off as the tumor moves in and out of the beam's path, strike the entire area in which the tumor moves (but this poses a risk to more healthy tissue), or try and time the tumor's movement to the movement of something else like the patient's diaphragm and move the beam in sync with that. Of course all of these rely on how you observe the tumor's motion which is no easy task. There are a handful of imaging options, but none of them perfect; it's hard to image the tumor and deliver treatment at the same time, or to see the exact boundaries of many tumors. In some cases doctors can use injected bio markers to identify the tumor, but this is also limited to bio markers that are available. You can also try to predict the path of the tumor, and scientists are working on software programs to generate a projected path of a tumor based on measurements of its unique motion. An ideal system will incorporate more than one of these methods, and link them together into a comprehensive model that changes and adapts to the tumor's location in real time.

The title of this year's meeting was "Frontiers in Quantitative Imaging for Cancer Detection and Treatment," and I must say that the entire thing was sobering. I'm used to attending basic research science talks, where the stakes are not nearly as high as they are for many of the people at this conference. It was very inspiring to see so many motivated, passionate people actively working toward solutions to all these problems. Can't wait for next year.

Frontiers in Physics: A Short Piece on Opto-genetics

2009-08-03T08:52:49Z

A quick note about the third talk in the "Frontiers of Physics" session, this one delivered by Karl Deisseroth, an assistant professor of bioengineering and psychiatry at Stanford University. Deisseroth and his team have been experimenting with implanting halo rhodopsin pumps into mammalian brains. These pumps occur naturally in alae, which have no brains and so rely on external light cues to tell them when to move and react. In mammals, an optic fiber running into the skull causes ion-channel excitation in cells, which induces some sort of change in the body. The light stimuli can cause the mouse to do different things, like run in a circle or wake from a deep sleep, and the team believes they will be able to use different colors to stimulate different behavior. (Image credit: Raag Airan et al., Stanford University)

Frontiers in Physics: Particle Accelerators

2009-08-03T04:20:38Z

Joseph Lykken of Fermi National Accelerator Laboratory gave a great talk discussing the many ways we use accelerators today, and from there what we will expect the next generation of accelerators to do. For the non-physicists in the crowd it was a helpful overview and at such an interdisciplinary meeting it never hurts to explain the fundamentals.

The big news in accelerator physics these days is the restart of the Large Hadron Collider at CERN in Geneva (shown above with the underground tunnel illustrated above ground). With a price tag of $10 billion and a time line of 20 years to build, Lykken emphasized the empirical trouble with operating such a machine. As the largest piece of machinery in the world as well as one of the most complicated, the LHC holds twenty seven kilometers of wiring, magnets, cooling systems and advanced technologies. You're bound to run into a few bugs, like those that shut down the machine last September. But the LHC is on schedule to restart this fall when scientists will get to fullfill their ambitions of finding a particle that gives matter mass, uncovering the nature of dark matter, and recreating conditions during the big bang. The science it hopes to produce is truly tantalizing for scientists and science lovers everywhere.

The LHC is the largest and most powerful accelerator in the world, but the field also expands horizontally into smaller, yet equally important applications. There are, of course, medical applications such as proton therapy which treats on the order of 8,000 patients a year at 25 proton therapy centers in the US. There are even more biological applications at synchrotron light sources: accelerators that give off X-rays as they drive particles around a circle. These powerful X-rays are becoming a standard part of protein crystallography, and offer many other biological applications. Soon the first free electron laser will start up at SLAC National Accelerator Laboratory and offer scientists a chance to watch incredibly fast processes such as protein folding and molecular motion in real time.

Accelerators may even give aid to the energy crisis and reduce global warming. Accelerator scientists may totally revamp nuclear power by developing a type of accelerator that drives a thorium reactor (rather than uranium or plutonium which are limited resources as well as major safety issues). The waste from these reactors would have a half life of 30 years, instead of thousands. The device would require a linear proton accelerator with particle energies of 10 megawatts, which does not exist yet, but plans are stirring.

Scientist all over the world are contributing to plans for a project called the International Linear Collider, or ILC, a 31 kilometer electron-positron collider that would compliment the LHC. No country has granted space or funding yet, but there are already over 2,000 collaborators from 300 countries working on preliminary plans.

Fermilab, Lykken's home institution, continues to reach for the cutting edge of accelerator science in the US. Fermilab hosts a premier proton therapy center, and is home to the country's most powerful proton-antiproton accelerator, the Tevatron, which will lead the hunt for the Higgs boson until the LHC comes back online. Fermilab has plans to continue leading the field by hosting at least one of two proposed next generation projects. The first, Project X, would be the first superconducting linear collider, the advantages of which are increased stability and lower wall-plug power consumption. There is also buzz for the first muon collider at Fermilab. The lifetime of a muon is less than a microsecond, so the challenge for building such a machine is trifold: create, collect and make a beam out of these particles in less than a microsecond. The collisions would provide new physics to study and save energy and reduce size.

Particle physicists certainly want to push the upper limit of accelerator power, but to go any bigger than the LHC would begin to cost in the hundreds of billions of dollars, which would require some major justification. So the next generation, if they hope to continue to push the energy limits, must eventually reduce in size. This would not only mean big accelerators with even more power, but also making small accelerators smaller; so that, for example, proton therapy devices could it inside an office rather than a football field.

The leader in such technology comes from plasma wakefield accelerators, where particles sit in a plasma (rather than a vacuum) and in one version are accelerated with lasers. One bunch of electrons actually catches a ride on the wake of a bunch in front of it - like a water skier behind a boat. These accelerators could move particles to the same speeds as current technologies, but at 1/1,000^th the distance.

"The traditional R&D model for new accelerator technologies has been that the particle physicists...do this R&D and everybody else benefits from [it]," said Lykken. "This model has worked very well in the past; it's still working. But if we really want...to turn around the time from the basic accelerator technology development to something you can use in a hospital, we need to get closer connections between the people doing this kind of research and the people that know what they want to use it for."

Frontiers in Physics: Real Time DNA Sequencing

2009-08-02T16:04:32Z

It took scientists more than twenty years after the first DNA sequencing technology was discovered to sequence the entire human genome; yet our own cells complete this task every time our bodies produces a daughter cell. So to achieve the goal of real time DNA sequencing, Pacific Biosciences had the idea to spy on Mother Nature as she goes to work copying DNA. Now, the company's commercial device planned to be on the market in 2010, promises to be 20,000 times faster than current second generation technology, with turn around time of about ten minutes rather than ten days. Chief Technology Officer Steve Turner says in four to five years, new technologies promise to rocket this technology forward even further, making it will possible to sequence an entire human genome in fifteen minutes, on a chip that costs less than 100 dollars.

DNA polymerase is a natural enzyme that constantly makes copies of DNA. DNA is a double stranded chain, and when the two strands are separated, it's possible to recreate one based on the other. That's because DNA consists of only four building blocks, or nucleotides. Each nucleotide only pairs up with one other: adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C). Thus, if one side of the chain reads AATTGGCC, the other side reads TTAACCGG. Polymerase unzips a DNA chain and as long as there are nucleotides to be had, it grabs them and makes a copy of the chain.

Second generation DNA sequencing techniques use polymerase as a reagent, throwing it away after reading only a few nucleotides in the sequence. Turner says one of his company's main objectives was to achieve what they call Single Molecule Real Time DNA Sequencing (SMRT DNA sequencing) in which they keep the polymerase around longer. One the main problems with watching the polymerase is knowing how to see the nucleotides. Second generation techniques attach a different color fluorophore molecule to each type of nucleotide, lighting them up like Christmas lights. But a whole chain of these lights creates too much background noise to see the individuals and their order on the chain.

Pacific Biosciences overcame this first challenge by attaching the fluorophores to a part of the nucleotide that is naturally cleaved off by the DNA polymerase. It diffuses away with 100% efficiency in a totally natural process, and keeps the background noise to a low minimum.

To illuminate the individual nucleotides as they are attached to the chain, the company has developed a SMRT chip- a strip of metal with thousands of small wells in it (see image). At the bottom of each well is a polymerase, resting on a glass bottom, and latched onto a strand of DNA which it will unzip and begin to copy. Base pairs fly around the surface of the chip, but only a few at a time dip down into the well. This immediately minimizes the background noise from those unattached nucleotides. Engineers shine a laser through the glass bottom, but the light does not come up through the well. This uses the same concept found in your microwave oven. You don't want those microwaves flying around the kitchen, but you want to see what's cooking. So the door of the oven has small holes cut in it, which are large enough to let visible light escape, but too small for microwaves to pass through. Similarly, the wavelength of the laser light is too large to pass up through into the wells. But there is an evanescent penetration volume of only a few zeptoliters (10^-21). This illuminates the polymerase, but not the space around it where the nucleotides are floating. And when a nucleotide is bound to the DNA cahin, it releases a burst of light.

The Pacific Biosciences technique uses no reagent, unlike second generation sequencing methods which use a tremendous amount of reagent (it would take two semitrailers full to sequence an entire human genome). It's 20,000 times faster and only takes ten minute to turn around from the time the sequencing finishes. In addition, the Pacific Biosciences it has three times the read time - or the length of a DNA strand that is read sequentially before the process stops. Normally this is shortened by an overwhelming background noise.

Considering that the technique utilizes a lense and a single-photon CCD array to collect the light, Turner says he hopes DNA sequencing will come to be considered a type of medical imaging in the next ten years.

Nanotechnology to Treat the Most Deadly Cancer

2009-08-02T16:02:57Z

Pancreatic cancer strikes less than 2% of the population, yet this brutal disease has one of the highest mortality rates among patients, with a mean survival time of only four to six months after diagnosis. Scientists hope that early detection will be the key to increasing patient survival rates, and Dr. Kimberly Kelly from the University of Virginia has dedicated her research to learning more this deadly cancer. Within the year her team hopes to go to clinical trials with new biomarkers to target early indicators of the cancer, as well as stem cells left over after removal.

Kelly's strategy begins with bacteriophages: viruses that bind to bacteria and cause them to create millions of copies of the virus phage. In a technique developed some years ago, scientists attach a random amino acid sequence to the bacteriophage which causes the host bacteria to also generate millions of random peptides. Kelly and her team take this zoo of peptides and throw them up against pancreatic cancerous cells and see what sticks. Peptides that "stick" to the cancer cells are chemically bound to proteins on the cell surface and become new biomarkers for those cells. This technique can be used for any cancer or disease and requires very few lab resources, as the peptides can all compete for the cancer cells at the same time so they don't need individual handling or individual tissue samples. It's also very fast. The trade off, says Kelly, is that it may not find all of the cell surface proteins, but it will find the high expressers. They've identified about thirty where there could be tens of thousands on the cell surface.

After finding a group of desired peptides and producing them synthetically, the team worked to attach marker molecules to the peptides. Thus, they can inject the patient with the peptide, which will bond to the cancer cells, and the marker will appear in a scan of the patient. An iron oxide molecule will appear in an MR scan, and an indium molecule will appear in a SPECT scan. The team is looking for cancer cells as well as cancer stem cells and pre-cancer lesions. The lesions may help in early detection, while stem cells left behind after tumor removal are often what cause recurrence. This targeting of specific cells could provide information about what type of treatment doctors should pursue in individual patients or eventually assist in targeted drug delivery.

Their progress is approaching a critical phase as they hope to have the first human trials ready within a year. They are in the process of completing preclinical trials and toxicology tests. The first steps will be small; simply making sure the biomarkers work in humans, and then identifying pre-cancer lesions. Ultimately, she says, early detection and treatment is the goal.

Carbon Nanotubes Help Cook Cancer

2009-07-31T17:33:50Z

It seems that one out of every few fictional villains ends up resorting to the same method for destroying the earth: hitting it with a giant laser. Although these fictional plans never elaborate on the real world physics, in some ways the villains have the right idea. Lasers are powerful tools and simply used as a heating device, they can kill cells. Thermal therapy is being used to kill cancer cells in tumors that other methods fail to eliminate, but as with radiation therapy there is a risk of overheating healthy cells, or not heating the tumor cells enough.

A new idea for improving thermal therapy was recently published in PNAS and presented at the AAPM session "Frontiers in Medical Physics," by the young research assistant Xuangfang (Leo) Ding from Wake Forest University. Using multi-walled carbon nanotubes (MWCN's - shown above) Ding and his collaborators hope to make guided laser cancer removal safer and more effective.

The treatment injects cancer tumors with MWCN's, and uses a guided near infrared laser to heat them up and deliver a fatal temperature rise to the cancer cells. The laser pulse is low energy (3 W/cm²) and fast (30 seconds per dose). The team uses Magnetic Resonance Temperature Imaging, MRTI, to identify the tumor and then to monitor the tumor's temperature as well as the temperature of the surrounding tissue. Trials with mice showed a significant rise in the temperature of the cancer cells injected with the MWCN's, compared to without. And, the tumors were far less likely to come back.

The treatment can be used non-invasively on superficial tumors like skin cancer, and with minimal invasivity to deeper tumors by inserting a small laser optic fiber into the target as well as the MWCN's. The exception is lung cancer, where the motion of the tumor would cause too great an error in the MRTI.

Since carbon nanotubes are not approved by the FDA, it's uncertain when the team can begin clinical trials, and they are still investigating any potential side effects of the MWCN's.

Photon Counters for CT Scans

2009-07-31T14:08:19Z

Developments from CERN could make CT scanners even better at detecting early cancer cells or other disease indicators. The facility's work to create photon counters that can count ten million photons per second - up by a factor of one hundred from previous generation counters - have been integrated into CT systems and had their first trial run with patients. There are more developments that will have to take place before the photon-counters can fullfill their full potential, but early work presented at the meeting looks promising.

While CERN made the progress in photon counter technology, it has been representatives from industry who put them together with CT scanners. At the AIP and AAPM meeting, Reuven Levinson, a Technology Development Leader at GE Healthcare in the CT Engineering group in Haifa, Israel, announced the first use of a photon counting CT system on human patients. The CT's X-ray detector counts the individual photons and measures their energy. Levinson and his team built the photon counting CT system and had it installed last year at the Rabin Medical Center in Tel Aviv, Israel.

CT scans, introduced in the 1970's, revolutionized X-rays by giving doctors a sharper look inside their patients. Traditional X-rays can only produce straight on 2D- projection images, while CT scans provide cross sectional slices; revealing internal structures otherwise concealed by overlying layers. In hospitals, CT scans are helpful, and in many cases irreplaceable, in diagnosing diseases and injuries like internal bleeding, strokes, and lung disease. In the US, 68 million CT scans are performed year.

One of the requirements for CT scanning is that the image must be acquired quickly. As with photography, if the patient moves during the scan, the final image will be blurred, so modern CT scanners capture an image in less than 1 second.

These modern CT systems use x-ray detectors, which operate much like digital cameras, with the exception that the CT detectors essentially produce "black and white" photos. The detectors only record the total energy of all the x-rays transmitted through the patient's body, not the individual energies of each photon. In the optical range, the energy of a photon determines its color, so the CT scanners are in a sense color blind.

And for the most part, CT scanners don't need to see individual photon energies. For the majority of uses, the black and white photo tells the physician everything they need to know. But in some cases, "color-sensitive" X-ray detectors would be beneficial.

Previous generations of photon counting detectors could count up to only 100,000 x-rays per second, which was not fast enough to produce an adequate CT image.

That was until about five years ago when particle physicists at CERN, the facility in Geneva that is home to the Large Hadon Collider, broke the previous barrier of photon counting by ten orders of magnitude. In need of highly sensitive detectors for their experiments hunting subatomic particles, they increased the capabilities of photon counters to over 10 million photons per second. This increase would allow a photon counter to measure the energy of each individual photon striking the detector from a CT scan.

The results reported by Levinson explained the first use of the photon counting detecor on humans, yet this can not yet assist in detecting specific types of cells. To highlight specific cells that the CT scans can target, the team would like to attach nanoparticles that the photon counter CT system can easily detect - such as gold or other metals - to biomarkers that will attach to the target cells. So, attaching gold nanoparticles to a peptide that bonds to "vulnerable" plaque cells will illuminate the cells in little gold halos. Another company has reported results using the gold nanoparticles in rats and rabbits.

Eventually the same technology could also be used in cancer detection. While many cancerous tumors are visible on regular CT scanners, there are significant limitations. A CT scanner cannot distinguish between cancer and normal tissue following radiation or chemotherapy treatment. The imaging of a tumor following the anti-cancer treatment is critical in determining the patient's status and also in evaluating the efficacy of different treatments in curing the cancer. Current medical practice utilizes PET/CT for the status evaluation of post-treatment cancer patient, which is an expensive and time consuming procedure. The challenge would be for CT plus nanoparticle systems to replace the PET/CT procedure with a simpler, higher resolution and less expensive alternative.

New Ideas for New Accelerators

2009-07-30T12:07:10Z

One of the largest disadvantages of therapies that require accelerators is the size and cost of the accelerators themselves. These factors limit who can receive care and where. So for medicine and the future of accelerators in general, the community is pushing for smaller and more affordable (but of course, that's the case with all technology isn't it?). At a very intriguing session I got to hear about an approach that a group of scientists at Stanford University and Fluence LLC are developing to make smaller particle accelerators for medical applications. They are also collaborating with the Stanford medical school and SLAC National Accelerator Laboratory, who are contributing expertise in Monte Carlo simulations for beam transport and dose calculations.

Their technique is called electromagnetic plasma acceleration (not to be confused with other plasma accelerators that use lasers) and it goes something like this: get a neutral gas in-between two electrodes and let it break down into electrons and ions. The currents that flow through the plasma then generate their own magnetic field (this is a big advantage because no magnets are needed); this exerts a force to the right, and the electrons start to move.

This alone is not a new approach. But normally the ions upstream form a wall, sort of like a piston, and push the other particles forward. This works for lower energies, but when one tries to accelerate the piston faster it starts to tilt and downstream gas can blow by it without being accelerated. This is like a piston with a hole in it, which doesn't push anything. So there's a definite limit to how fast you can get those particles to move.

But new research has shown that you can make tweaks to the system and cause the piston wall to disappear. Early work performed on this topic by Dah Yu Cheng in the 1970's already showed that there are two ways to accelerate these particles. One (the piston) moves the particles like an explosion. The other moves them the way a jet engine does, in a more jet or bullet-like shape that is also more efficient. The Stanford team is now trying to understand this second mode of acceleration. While there was previously a limit on how fast you could accelerate the particles until the piston tipped, this limitation does not apply to the second mode. They've got particles moving at around 100 keV, which is still far short of the 100 MeV's needed for proton accelerators, but that's what the Stanford team is dedicated to reaching. They'll have other challenges as well, including reducing the wide energy distribution that the particle jets tend to have.

Flavio Poehlmann, who delivered the talk in place of professor Mark Cappelli who was unable to attend, said the team expects another ten years of work before they reach their energy goal. They're currently in the process of submitting patents before they publish any papers on the subject.

MRI Breast Screenings and Biopsy

2009-07-29T22:34:00Z

At a meeting with such a heavy emphasis on breast cancer, Debra Ikeda's talk offered some great information to put all of the new innovations into focus. While most of the speakers were medical physicists working at the cutting edge of technology, Ikeda is a professor of Radiology at Stanford and is working to better define a standard of care for breast MRI and MRI biopsy. So her view of the problem stems from a growing understanding of the biological nature of breast cancer and the problems that face doctors in the field. "I just want to say as a radiologist that I'm very excited to hear about what you guys are working on," Ikeda said to her fellow presenters.

Breast cancer originates near the root of the milk ducts in the breast, and cancerous cells can move from the ball-shaped root down the ducts. This early form of breast cancer, known as ductal carcinoma in situ (DCIS), is very difficult to detect. Later on the cancerous cells can break out of the ducts and become invasive, growing into more recognizable tumors. While Ikeda promoted MRI treatment, she noted that traditional mammography is actually 25% more effective at identifying this early stage of breast cancer than MRI.

Most breast cancer patients have their entire breast radiated after the removal of a tumor, to eliminate the risk of the cancer returning through the ducts. Because each breast has multiple ducts, there can be multiple cancer foci in the breast.

Typical tumors usually possess a very high amount of blood vessels. This is one easy to way to spot a tumor - by injecting the patient with a marker or angiogenesis drug, a tumor will uptake the injection faster than the rest of the breast because of the number of blood vessels (although this isn't always the case).

MRI is more effective than traditional mammography in identifying tumors, especially in high risk patients with dense breast tissue (Ikeda does note, however, that they should be used together, as they both have their advantages). One study of over seven hundred US practices showed that three quarters offer MRI for breast cancer screenings, although the majority of those only do about 5 a week (which is relatively low). 31% percent of those, however, do not do MRI biopsy, which Ikeda believes needs to change. A biopsy is an invasive process that takes tissue samples from an identified abnormality and identifies it as cancer or benign. "It's important to be able to biopsy when you see something abnormal," says Ikeda. "It would be horrible to be told 'You've got something...but we can't biopsy it.'" Ideally of course, methods would increase for discerning between benign lumps in the breast without the need for biopsy.

To more fully understand exactly what physicians will see on MRI scans of different patients, how to look for signs of early cancer, and what standard screening steps to take, Ikeda sits on the BIRAD Lexicon Committee, which constructs the yearly ACR Atlas. The Atlas will compile information to hopefully answer those questions, but it will rely on detailed information from physicians.

The committee's requests to radiologists include doing bilateral screening in patients (comparing both breasts), comparative studies among patients, and careful descriptions background enhancement.

Background enhancement describes how much of the dense tissue in the breast is enhancing; it's more of a change in the dense tissue rather than the volume of dense tissue. Background enhancement can change due to natural hormone cycles which can fool an MRI into looking like cancerous tissue Different types of background enhancement filters can better differentiate dense tissue fluctuations.

Four to five percent of women who develop breast cancer will develop it in both breasts, so Ikeda emphasizes the need for doctors to do bilateral care and report their findings. The bilateral studies also make it easier to identify abnormalities in each breast.

As I mentioned before, breast cancer imaging, screening, diagnosis and treatment were discussed in more sessions than perhaps any other topic on the IPF agenda. While the science was all fascinating, this session brought home the human aspect of all the research. It was held in memoriam of Carolyn Kimme-Smith, a leading radiologist in the field of breast cancer study who also suffered from breast cancer. Ikeda began her talk with a quick tribute of her own to Kimme-Smith, saying she was always kind to and respectful of other people, even when their ideas conflicted.

A Gamma Camera for Molecular Mammography

2009-07-29T11:14:48Z

Speaker Michael O'Connor cited a study by the National Cancer Institute which shows that in women with dense breast tissue, traditional mammogram successfully identified cancerous tumors only 40% of the time, and ultrasound 43%. But MRI successfully spots cancerous tumors at 80%. Women with dense breast tissue have a significantly increased risk of developing breast cancer, yet the sensitivity of mammography drops with tissue density. It's a frustrating contrast especially because offering these women MRI's isn't a fiscal option, as they cost about $3,000. Even with health insurance, this might not be an option for many women.

For the past six years, O'Connor and his colleagues at the Mayo Clinic have been investigating different molecular imaging techniques for screening for breast cancer, in the hope of finding a cheaper, equally reliable method to MRI. They've focused many of their efforts on scintigraphy, which images the body by catching gamma rays emitted from the patient (thanks to an injected radioactive tracer), rather than passing X-rays through them. But this technique has been difficult to apply to breast imaging because it's tricky to get the breast into the field of view of the camera without missing segments or getting signals from the rest of the body as well (which washes out the resolution). Thus, many groups are working on small field of view gamma cameras, with only one currently commercially available.

The gamma camera itself contains crystals that respond to the gamma rays by emitting a little pop of light. Collectively they create an image. O'Connor and his colleagues are putting their money on Cadium Zinc Telluride (CZT) crystals, which are currently a bit pricey, but they believe the cost will drop when they're made commercially available. These crystals can be operated at room temperature (some detectors had to be cooled to liquid nitrogen temperatures which would be a bit chilly for breast imaging!), and they have no "dead space" so you can get very close to the breast tissue.

The resolution on the scintimammography (so called when imaging the breast) using CZT crystals is striking. O'Connor showed mammography images of a breast that appeared to have no tumors or other build up, and then showed the image of the same breast imaged under the gamma camera. The tumors appeared as clear as day in the gamma image; but were completely invisible to the mammogram. In a clinical trial of dense breast tissue the gamma camera caught 10 tumors out of twelve while the mammogram only caught three. Its resolution is comparable, but not better than MRI.

Two vendors are working on making the technology commercially available, and O'Connor estimates the cost of the procedure will be about $400.

But there are some key drawbacks that O'Connor and his colleagues are still working on. First, there are some false positives from the gamma camera, identifying non-cancerous objects like pampillomas as tumors. Secondly, while the radioactive tracer is FDA approved, the treatment delivers a dose of radiation 6-7 times larger than a mammogram. While this is still below the level of natural background radiation, the group is "very sensitive" to the size of the doze and are trying to reduce it for both the patients and the radiologists who deliver the treatment.

President's Symposium: Present and Future Role of Computers in Medicine

2009-07-24T18:42:33Z

Computer scientist Ian Foster admitted in front of a few hundred medical physicists that he steered clear of anything to do with biology or medicine for many years. Hailed as "the father of grid computing," Foster (shown left) has always been highly focused on computer science and has subsequently garnered a very impressive resume. But the crowd didn't hold it against him, because recently Foster's had a change of heart, and says healthcare is presenting many fascinating challenges for computer scientists.

As the medical community accumulates an ever growing sea of information, data, clinical trials, research, ect. ect. ect....how can the community hope to transform all that information into useful knowledge? In his talk Foster presented a compelling case for a growing theme in the medical community known as quantitative medicine,which would attempt to answer this question. It starts with computer science.

Thanks to increase computer capabilities, biologists have been able to construct a map of the human arterial tree, and thanks to lowered storage costs, gene banks can store tens of billions of base pairs. It's easy to share high resolution images over the internet or through file sharing programs. There's no doubt medicine has entered the information age.

But, more information does not always mean more knowledge. "We should be thinking about new ways of knowing," says Foster. He links Aristotle's notion of empiricism (go out and experience the world if you want to know it), Newtons laws, and more recently the science of simulations as paradigm changes in ways of knowing. The next link in that chain, he says, will be finding way to organize and then utilize the vast amounts of data we can obtain.

Quantitative medicine aims to take advantage of the vast amount of data available, and ultimately use it to promote more individualized medicine. When doctors diagnose patients based on a set of symptoms, there remains a degree of qualitative treatment. In this information age there are more ways than ever to treat patients quantitatively, but that relies on comparing information on a massive scale.

Foster gives an example of lymphoma. In the 1950's this was diagnosed as disorders of the blood, and survival rates were very low. Today we know an incredible amount about the many varieties of this disease, and yet it can still evade a physician's analysis. 17% of patients with what's known as Burkitt's lymphoma are misdiagnosed as having diffuse large b cell lymphoma. The correct treatment for Burkitts have very high success rates; but an incorrect treatment for diffuse large b cell lymphoma almost always leads to death.

In the case of Burkitt's lymphoma, spectrographs of gene expression in the patient can indicate which disease the patient is likely to have. There is also evidence that the two diseases produce different effects in the brain, which can be detected in brain scans. Imagine if doctors had access to these images from other Burkitt's patients, which they could then compare with their own patients. They could reduce or eliminate that 17%

The challenges of establishing an organized, connected data base of this information are mighty. Namely, this isn't simply a question of uploading information to a cloud or grid. It would require a more interactive, closely linked system to connect members of the community with the right information; to help them find out what information they need. Foster uses this quote from the NRC Report on Computational Technology for Effective Health Care: Immediate Steps and Strategic Decisions (2009): "...have to pay attention to cognitive support...computer-based tools and systems that offer clinicians and patients assistance for thinking about and solving problems related to specific instances of health care."

For all this to happen, Foster says small groups within the health care system need to come together and form virtual organizations (VO's) - groups with no official affiliation, but who have some agreement about their desired outcomes and the certainty of those outcomes. These small groups may begin sharing information, images and data and communicating to figure out the best ways to utilize the growing database. This will require new channels of communication from basic research labs, to clinics and up to hospitals.

There are already examples of medical institutions instigating this kind of system, including the South Side Healthcare Collaborative in Chicago, the Neuroblastoma Cancer Foundation and the Children's Oncology Grid. The COG is already sharing images from clinical trials through public servers that can be accessed by tens or even more than a hundred participants. For the COG, information is already harder to come by than with adult cancers, so the sharing program was highly sought after.

But for some groups, this may not be the case. It's true that one of the most difficult aspects of forming these VO's will finding incentives for people to participate. The activities required will demand time, resources and money. What's crucial to all these systems is human interaction, either through specialized software or more immeidate contact. "These are human systems," says Foster. Ultimately, the community will have to make some sacrifices if they hope to have their vast amounts of data mean anything.

The morning of the President's Symposium, TV's in the hotel lobby showed news of the continued debate among policy makers over the proposed health care reform bill. This is one of the largest issues bearing down on our nation at the moment, and may change the way medical institutions are linked together. But Foster emphasizes that the change must begin on the small scale, with small VO's that grow and change and accumulate other groups.

Foster wraps up with a quote from his colleague Alan Kay (from 1997): "The computer revolution hasn't happened yet." For healthcare, he says, it still hasn't.

Helllllooooo Anaheim

2009-07-24T15:21:57Z

Hello from lovely Anaheim, California. I'm Calla Cofield and I'll be your main blogger for this year's AIP Industrial Physics Forum. For the past few years Jennifer Oullette has created some magnificent posts from the IPF, but she's busy these days running the Science and Entertainment Exchange as well as writing yet another book. I'm absolutely thrilled to take on this assignment.

This year's IPF titled "Frontiers in Quantitative Imaging for Cancer Detection and Treatment," and is being held in conjunction with the American Association of Medical Physicists annual meeting.

The AIP IPF takes place at that crucial juncture where basic research and application meet. It's very important for scientists, engineers, and medical professionals to communicate at this locale, so that basic research isn't lost before it can develop into useful applications, and so specific needs of industry professionals can be directly addressed by researchers. It also serves as a reminder to the general public that technological advances that impact our lives, begin with basic research.

At the opening reception I got caught up talking with a member of the AAPM Scientific Program Committee, which plans sessions for the meeting. He's worked as a medical physicist for some time and said that once upon a time the fields of medical imaging (handled mostly by physicists) and radiation/oncology were separate and distinct. But more recently, he said, the two are coming together. While medical imaging is used by all branches of medicine, oncologists and radiologists are utilizing imaging techniques more than ever in treatment and diagnosis. Some would argue that for cancer detection and treatment to be most effective, new imaging technoogies need to be developed with the specific needs of oncologists and radiologists in mind. This is a major theme at the meeting.

So it will no doubt be a jam-packed few days and I'm already relishing the thought of so much physics under the warm Anaheim sun.