Optics meets medicine at US Optical Society meeting

16 October 2008

Medical research is a cornerstone of Frontiers in Optics 2008 (FiO), the 92nd Annual Meeting of the Optical Society (OSA), being held Oct. 19-23 at the Riverside Convention Center in Rochester, New York. FiO 2008 will take place alongside Laser Science XXIV, the annual meeting of the American Physical Society's Division of Laser Science. www.frontiersinoptics.com/

Medical research highlights at FiO

The following are a few of the many technical highlights to be discussed at the meeting.

  • a new look at mini-strokes;
  • a potential new tool for brain surgeons;
  • new technique for mapping blood supply in retina increases safety, comfort of exams;
  • the optics of alzheimer's disease;
  • potential non-invasive optical detection of pancreatic cancer;
  • The Neuron microscope, treating bone cancer and futuristic lighting at FiO.

A new look at mini stroke

Like a burning fire, the brain is in constant need of oxygen, and when a blood vessel is blocked during a stroke, part of the brain becomes starved of oxygen and nutrients. When this happens, neurons in that part of the brain die off, leading to permanent loss of function in the parts of the body those neurons serve. The word stroke is usually associated with the blockage of a large blood vessel that leads to devastating loss of brain tissue, but small blood vessels get occluded too, and much more frequently than their large counterparts. These mini-strokes can be so small it is not even apparent when one has occurred, yet clinical research has shown that the more of these small strokes an individual has, the more precipitous their cognitive decline will be as they age.

Little research has been done to study the effect of blockages in small blood vessels on the health and function of nearby neurons. Part of the problem has been that there were no good ways to produce blockages in small venules in the brain of an animal model.

Now Cornell University doctoral candidate John Nguyen and his advisor Chris Schaffer have developed an animal model for looking at the effect of small strokes in the tiny venules in the brain of rodents. They are using a powerful laser and nonlinear optics to target and clot vessels of the venule system and then monitor the effect on blood flow in upstream capillaries in the brain. They find that blockages in venules can cause a significant decrease in blood flow in upstream capillaries, which in turn could cause the death of neurons.

These findings suggest that small occlusions in the venule system may play a role in cognitive dysfunction. Pockets of dead tissue, perhaps caused by venule occlusions, are often seen in autopsies of people who had dementia late in life, says Nguyen, and now researchers have a way to study this phenomenon.

Presentation FTuE3, "Femtosecond Laser-Driven Photodisruption to Induce Single Venule Occlusions in Rodent Brain," Tuesday, Oct. 21, 9 a.m., Highland E, Rochester Riverside Convention Center

A potential new tool for brain surgeons

One of the primary ways of treating brain cancer is surgically removing the tumours. The risk of this sort of procedure is obvious — it involves cutting away tissue from the brain, potentially severing nerve fibres and causing neurological damage. MRI and CT scans can reveal the extent of tumours, but only prior to surgery. These techniques rely on large instruments that cannot be used in the operating room, and during the operation the brain may relax and move, forcing surgeons to adjust where they are cutting to minimize the damage to the brain tissue.

During surgery, doctors make these adjustments by asking their patients to perform certain tasks while electrically stimulating parts of the brain bordering where they plan to cut. The electrical stimulation inhibits brain function in that region, revealing whether losing that tissue would cause permanent damage. Although slow, this is a good way to detect and protect critical areas of the brain.

Now Paul Hoy and his colleagues at the University of Southampton in England are developing a rapid and highly sensitive method for measuring brain function across the entire area during surgery. The method is based on observing blood flow in the brain. Active brain regions have increased blood flow, and this change can be observed by looking at light reflected off the brain because haemoglobin, the protein that ferries oxygen within the bloodstream, will absorb light differently depending on whether it carries oxygen or not.

Recently Hoy and his colleagues measured this signal on four people undergoing brain surgery and showed that their results agreed with the electrical stimulation. They hope that the technique will one day provide information quickly for neurosurgeons, and they are now collecting data that will lead to a clinical trial designed to test how effective the technique is.

Presentation FTuD3, "Optical Intraoperative Measurement of Function in the Human Brain," Tuesday, Oct. 21, 9:15 a.m., Highland D, Rochester Riverside Convention Center

New technique for mapping blood supply in retina increases safety, comfort of exams

Anyone who has ever been examined for eye disease involving blood flow in the retinal capillaries — as people with diabetes routinely are to assess vision loss associated with their disease — remembers the test: the injection, the bright lights, the discomfort.

Now researchers from the University of Indiana offer a new non-invasive technique using near-infrared light that allows them to see blood flow within all capillaries of the light sensitive tissues in the retina at the back of the eye. With it, they can detect changes in blood vessels while the patient remains shot-free and relatively comfortable. "Our work enables us to measure the smallest capillaries using near infrared light, without injection of contrast agents," explains Stephen Burns, who is leading the research effort at Indiana, "and thus it holds significant promise for safely investigating retinal vascular changes in disease."

The traditional means of visualizing the retina is known as fluorescein angiography. It involves a shot in the arm of fluorescein dye that travels within seconds through the blood to the eye where it highlights flow and vessel integrity in the small capillaries in the retina. A series of photographs is taken to document the capillary network and reveal defects or changes. If vessels are damaged or abnormal, dye leaks out. Many shot-adverse patients find the procedure repellent enough that they put off getting these crucial eye exams.

To develop a patient-friendly alternative, Burns and his colleagues turned to adaptive optics that uses a confocal scanning laser opthalmoscope to produce retinal images in real time. A mirroring system helps guide the imaging beam to build a montage of the area being investigated. "In general, we could generate maps within a single imaging region without operator intervention once frames were chosen for alignment," Burns says.

Presentation FWW6, "Constructing Human Retinal Capillary Maps from Adaptive Optics SLO Imaging," Wednesday, Oct. 22, 5:15 p.m., Highland E, Rochester Riverside Convention Center

The optics of alzheimer's disease

One of the hallmarks of Alzheimer's disease is the formation of plaques made of protein aggregates in the brain tissue. There is still considerable debate among scientists as to whether these plaques are the cause of the neuronal death that occurs in Alzheimer's or just a by-product of the disease, however. In the last decade, autopsies have revealed that people with the worst dementia often don't have the worst plaques, and clots and hemorrhages in small blood vessels have also been implicated in the disease.

New optical techniques may allow the link between altered blood flow and Alzheimer's disease to be studied further by enabling scientists to directly look at the effect of clots in the brain's microvasculature on the development of Alzheimer’s. Chris Schaffer and his colleagues at Cornell University use tightly focused femtosecond lasers to introduce clots in the microvasculature in the brains of rodents. The laser cuts open the cells lining the blood vessels, triggering natural clotting mechanisms and leading to the formation of an occlusion. The clotting process, as well as the subsequent changes in the brain, can be followed with fluorescence microscopy.

Schaffer and his colleagues are looking at whether putting tiny clots in the microvasculature can exacerbate Alzheimer's disease. Using transgenic mice that are predisposed to developing early-onset Alzheimer's disease, they have already shown that clotting a microvessel triggers the formation of new protein plaques. Next they plan to systematically study the effect of these clots on the cognitive decline of the Alzheimer's mice.

Presentation FTuE4, "Femtosecond Laser-Induced Microvascular Clots Trigger Alzheimer's Disease Pathology," Tuesday, Oct. 21, 9:15 a.m., Highland E, Rochester Riverside Convention Center

Potential non-invasive optical detection of pancreatic cancer

At the University of Michigan, a multidisciplinary team of researchers is investigating whether tissue optical spectroscopy can be employed for early cancer detection in the pancreas during minimally-invasive endoscopic diagnostic procedures. Their objective is to help physicians distinguish between cancerous tissue transformations and benign changes in tissues due to different diseases, such as pancreatitis. Doing this can speed correct diagnosis and treatment to produce better patient outcomes. Pancreatic cancer is the fourth leading cause of cancer death in the United States; 95 percent of all patients diagnosed with the disease will die from it, more than half within six months of diagnosis.

“Until better treatment approaches can be developed, the only opportunity to change disease-associated mortality in pancreatic cancer patients is earlier diagnosis," explains Mary-Ann Mycek, associate professor and associate chair of the Michigan’s Department of Biomedical Engineering. "Current diagnostic methods have not been able to provide accurate diagnoses in early stages of the disease."

The Michigan team’s goal is to develop an optical method to detect pancreatic cancer in patients at early stages—an advance that could greatly improve the chances of patient survival by meeting the critical, unmet need of accurately differentiating malignant masses from benign pancreatitis. Such improved diagnostic accuracy could also appropriately triage patients, thereby preventing those without cancer from having unnecessary surgery.

To do this, investigators used a multimodal optical spectroscopy approach based on observing reflectance and fluorescence properties of pancreatic tissue samples. Spectral analysis showed significant differences between normal, pancreatitis (inflammation) and cancerous tissues, thus suggesting non-invasive diagnostic possibilities for distinguishing among disease states.

The idea behind optically-based diagnostics is this: in the body, the presence of disease alters tissue properties, such as local biochemistry and structure. Optically-based disease diagnostic techniques can probe microscopic tissue alterations for signatures of disease, thereby leading to non-invasive diagnostics in living patients. Once detected optically, such diseased tissue may be treated. Because optical techniques do not require the removal of tissue, they could represent an advance in patient care over the invasive practice of tissue biopsy.

Presentation FTuK5, "Modeling Reflectance and Fluorescence Spectra of Human Pancreatic Tissues for Cancer Diagnostics," Tuesday, Oct. 21, 11:30 a.m., Highland D, Rochester Riverside Convention Center

The Neuron microscope, treating bone cancer and futuristic lighting at FiO

How we understand the brain today is akin to how Lewis and Clark knew the United States in 1803—its broad outlines were understood but much of its territory was still undiscovered. Part of the problem is that while we know the major functions associated with many regions of the brain and generally understand how individual neurons work, we do not have a good way of observing the brain in action on the level of individual neurons. Functional MRI is a powerful way to image the activity in entire areas of the brain, but it lacks the temporal or spatial resolution to image the firing of individual neurons.

A new way of observing the brain in action involves light. At Frontiers in Optics, Henry Liu will discuss how he uses a new technique called self-phase modulation imaging to measure neuronal transmission. Developed by Martin Fischer, Warren Warren and their Duke University colleagues, self-phase modulation imaging basically separates a signal from the background noise (largely scattered light). The signals, in this case, are tiny changes in the optical properties of neurons that occur when they fire. Normally, these optical changes are hard to measure because they are obscured by scattering, but sculpting the laser pulse (femtosecond pulse shaping) at very high update rates makes separation possible.

Liu and his colleagues have studied living neurons cultured on Petri dishes that come from a region of the rat brain implicated in Alzheimer's disease. They can activate the neurons chemically and observe them firing. So far, they have not developed the resolution to be able to see individual neurons firing, but they are working on pushing the technique to that limit. The technique has a lot of promise because it should be able to observe the firing of neurons non-invasively, with low enough laser power to be safely used in living animals. It may one day help as a diagnostic tool to predict the onset of Alzheimer's disease and monitor its progress. The technique would have to prove safe and effective in clinical trials before it is widely available, however.

Presentation FWD2, "Intrinsic Nonlinear Optical Signatures of Neuronal Activity," Wednesday, Oct. 22, 8:45 a.m., Highland E, Rochester Riverside Convention Center

Understanding bone an light interactions for treating bone cancer

Understanding how different kinds of bone tissue scatter and absorb light may be a key to devising a new multi-modal treatment for human bone cancer based on activating anti-cancer drugs with light.

To do this, researchers must do more than think outside the box—they must think outside the "slab." Here’s why: tissues are generally researched as uniform or layered slabs. Bone tissues have different optical properties and occur in a cylindrical shape. Refining a light-based treatment that is sensitive to these differences has traditionally been a challenge. Now researchers at Oregon State University and Oregon Health & Science University are changing that.

Explains Ph.D. candidate Vincent Rossi, the project’s lead researcher, "Not much is known about the optical properties of different bone tissues. We measure the absorption and scattering properties of bone by creating a two-layer system within the cylinder to give us a finer level of detail on light propagation within bone." Using a fiber optic system to send and collect light waves through bone, the team analyzes the scattering and absorbing properties of bone tissue using reflectance spectroscopy of wavelengths. Data from the two-layer system is modeled by computer programs that simulate the light distribution.

The treatment being investigated is called photodynamic therapy (PDT). It is used extensively to treat soft-tissue cancers; bone is the next frontier. At this stage of research bones from dogs are used. If validated in humans, here’s how PDT might function as part of a multi-modal treatment approach to bone cancer: after surgically removing tumors, a surgeon would place light-sensitive, anti-cancer drugs—which are easily taken up by cancer cells—in specific locations to retard recurrence. To activate the drugs with light, physicians would then use information from the Oregon team’s two-layer system to guide light delivery to the bone tissue. Says Rossi, "Getting enough light in the right place has been one of the limiting factors."

Presentation FTuK1, "Understanding Light Propagation in Bone for Photodynamic Therapy of Osteosarcoma," Tuesday, Oct. 21, 10:30 a.m., Highland D, Rochester Riverside Convention Center

More information

FiO 2008 will take place alongside Laser Science XXIV, the annual meeting of the American Physical Society's Division of Laser Science. www.frontiersinoptics.com/

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