Lasers ID Deadly Skin Cancer Better than Doctors

High-resolution images from a laser-based tool developed at Duke University could help doctors better diagnose melanoma, the deadliest form of skin cancer.

The improved diagnoses could potentially save thousands of lives and millions of dollars in unnecessary healthcare costs each year.

The tool probes skin cells using two lasers to pump small amounts of energy, less than that of a laser pointer, into a suspicious mole. Scientists analyze the way the energy redistributes in the skin cells to pinpoint the microscopic locations of different skin pigments.

For the first time, scientists have the ability to identify substantial chemical differences between cancerous and healthy skin tissues, said Thomas Matthews, a Duke graduate student who helped develop the new two-laser microscopy technique.

The Duke team imaged 42 skin slices with the new tool. The images show that melanomas tend to have more eumelanin, a kind of skin pigment, than healthy tissue. Using the amount of eumelanin as a diagnostic criterion, the team used the tool to correctly identify all eleven melanoma samples in the study. The results appear in the Feb. 23 Science Translational Medicine.

The technique will be further tested using thousands of archived skin slices. Studying old samples will verify whether the new technique can identify changes in moles that eventually did become cancerous.

Even if the technique proves, on a large scale, to be 50 percent more accurate than a biopsy, it would prevent about 100,000 false melanoma diagnoses, said Warren S. Warren, director of Duke’s Center for Molecular and Biomolecular Imaging and a chemistry professor. Warren oversaw the development of the new melanoma diagnostic tool.

cancertissueWarren's group has succeeded in using the laser pump method to locate two different types of skin pigments in skin tissue, which may better identify developing melanoma, said James Grichnik, a dermatologist at the University of Miami who was not involved in the study.

The work is limited to fixed tissue on slides, but holds promise for diagnosing melanoma prior to biopsy, and the increased diagnostic accuracy, without unnecessary biopsies, is where the new tool could have cost-saving potential, he said.

Melanoma is the fifth-most common cancer for males and sixth-most common for females. In 2010, U.S. doctors diagnosed nearly 115,000 new cases of the disease, with nearly 8,700 resulting in death. The cancer is also one of the few where the death rate is increasing.

Doctors typically use a light and a magnifying glass or tissue biopsy, where a pathologist removes suspicious skin cells and looks at them under a microscope, to spot signs of disease. But using a lens and a light is a “17th century” technique that is only 85 percent accurate, at best, and tissue biopsy is not much more reliable, Warren said.

In 14 percent of biopsy diagnoses, pathologists would disagree on whether or not the sampled cells were cancerous, according to a 2010 study published in the Journal of American Academy of Dermatology. The statistic implies that two pathologists would have opposing diagnoses on 214,000 to 643,000 melanoma cases each year, Warren said.

When studying biopsied tissue, doctors typically follow the “when in doubt, cut it out” philosophy. If they are not sure about the health of the skin tissue, doctors remove additional skin around the diseased cells. The first and second tissue biopsies can cost thousands of dollars. If the melanoma is thought have spread, patients may then have lymph nodes in their arms removed or undergo chemotherapy, which dramatically adds to treatment costs.

But not all of the extra treatment is necessary because not all of the biopsied tissues are actually cancerous. Doctors need a more accurate way to diagnose melanoma, Warren said.

In 2009, he received a $1 million Challenge Grant from the National Institutes of Health, which was part of the American Recovery and Reinvestment Act of 2009, to develop the imaging tool.

The highly specialized lasers are currently commercially available and would only need to be added to the microscopes pathologists already use to diagnose melanomas. The cost for the added instrumentation is about $100,000, which may sound like a lot of money. But if each false positive melanoma diagnosis costs thousands of dollars, having such an instrument available for questionable cases could considerably reduce health care costs overall, Warren said.

He added that suspicious moles would still have to be removed from a patient and then imaged to detect cancer.

Matthews is working on imaging skin cancers grafted on to mice to see if the tool could become a device dermatologists could use to scan a mole without removing it. A device like that would be much more expensive and would not be ready for a few years, Warren said. However, pathologists could begin using the lasers to study biopsied tissue now.

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UGA researchers develop rapid diagnostic test for common type of pneumonia

University of Georgia researchers have developed a technique that can diagnose a common type of pneumonia within minutes, potentially replacing existing tests that can take several days for results.
The researchers, whose findings are detailed online in the journal PLoS ONE, detected Mycoplasma pneumoniae, which causes atypical or “walking pneumonia,” in true clinical samples with over 97 percent accuracy using a recently-developed nanotechnology-based platform.

“If you can make a positive identification from a 10-minute test, then appropriate antibiotics can be prescribed, limiting both the consequences in that patient and the likelihood that it will spread to others,” said lead-author Duncan Krause, a professor in the department of microbiology in the UGA Franklin College of Arts and Sciences.

Krause and his colleagues built upon an existing technology called surface-enhanced Raman spectroscopy, which works by detecting spectral signatures of a near-infrared laser as it scatters off a biological specimen. They were able to enhance the Raman signal by using silver nanorod arrays to detect the tiny bacteria in throat swab specimens.

Krause, who also directs the interdisciplinary UGA Faculty of Infectious Diseases, compared the nanorod array developed by collaborator Yiping Zhao, director of the UGA Nanoscale Science and Engineering Center, to a brush with densely packed bristles, where each of the tiny silver rods extends out at a specific angle. The sample, such as bacteria from a throat swab, penetrates among the bristles, where the spectral signature produced by the laser is amplified and then analyzed by a computer program.

Krause noted that infections due to M. pneumoniae are very common yet difficult to diagnose. The bacterium is a major cause of respiratory disease in humans and the leading cause of pneumonia in older children and young adults.

“Walking pneumonia feels like a bad chest cold that will not go away,” he explained. “It can persist for weeks and even months and can cause permanent damage to the lungs if not diagnosed promptly. A delay in diagnosis extends the likelihood for complications as well as continued transmission of the infection to others.”

Krause said the device can be reduced to a size that could fit in a briefcase, although their testing is currently done only in a laboratory setting. “Our hope is that when we begin to explore the capabilities of this technology, it can be applied in point-of-care testing,” he added. “Then the impact becomes truly significant.”

Krause hopes the combined efforts of the research specialists in nanotechnology and infectious disease will eventually be able to determine if the technique is effective in detecting other pathogens in clinical samples. “We need to do a thorough job with mycoplasmas first,” said Krause. “Then we can go to other clinical samples and ask the same questions with other infectious agents.”

Funding for the research was provided by the U.S. Army Research Laboratory, the National Science Foundation and the Georgia Research Alliance.

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Mayo Clinic Study Using Structural MRI May Help Accurately Diagnose Dementia Patients

/PRNewswire / -- A new Mayo Clinic study may help physicians differentially diagnose three common neurodegenerative disorders in the future. The study will be presented at the Alzheimer's Association International Conference on Alzheimer's Disease on July 11 in Vienna.

In this study, Mayo Clinic researchers developed a framework for MRI-based differential diagnosis of three common neurodegenerative disorders: Alzheimer's disease, frontotemporal lobar degeneration, and Lewy body disease using Structural MRI. Currently, examination of the brain at autopsy is the only way to confirm with certainty that a patient had a specific form of dementia. The framework, which is called "STructural Abnormality iNDex" or STAND-Map, shows promise in accurately diagnosing dementia patients while they are alive. The rationale is that if each neurodegenerative disorder can be associated with a unique pattern of atrophy specific on MRI, then it may be possible to differentially diagnose new patients. The study looked at 90 patients from the Mayo Clinic database who were confirmed to have only a single dementia pathology and also underwent an MRI at the time of clinical diagnosis of dementia. Using the STAND-Map framework, researchers predicted an accurate pathological diagnosis 75 to 80 percent of the time.

"The STAND-Map framework might have great potential in early diagnosis of dementia patients," says Prashanthi Vemuri, Ph.D., a senior research fellow at the Mayo Clinic aging and dementia imaging research lab and lead author of the study. "The next step would be to test the framework on a larger population to see if we can replicate these results and improve the accuracy level we achieved in this proof of concept study. In turn, this may lead to better treatment options for dementia patients."

The senior author of this Mayo Clinic research study is Clifford Jack, M.D. Other members included Kejal Kantarci, M.D.; Matthew L. Senjem; Jeffrey Gunter; Jennifer Whitwell, Ph.D.; Keith Josephs, M.D.; David Knopman, M.D.; Bradley Boeve, M.D.; Tanis Ferman, Ph.D.; Dennis Dickson, M.D.; and Ronald Petersen, Ph.D., M.D.

This work was supported in part by National Institutes of Health (NIH) grants, Robert H. Smith Family Foundation Research Fellowship, Alexander Family Alzheimer's Disease ResearchProfessorship.

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New Uses for Old-Line Diabetes Monitoring Test: Screening and Diagnosis

A blood test currently used as the gold standard for monitoring people already under care for diabetes may have far wider use in identifying millions with undetected diabetes, a team led by a Johns Hopkins physician suggests.

The hemoglobin A1c test (HbA1c), based on a blood sample, is widely used to keep tabs on how well confirmed diabetics keep their blood sugar, or glucose, in check by showing how much glucose red blood cells have been exposed to for the past 120 days, the average lifespan of these cells.

"The test is a measure of long-term glucose control, but doctors don't typically use it to screen for or diagnose the disease, " says Christopher Saudek, M.D., professor of endocrinology and metabolism at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Comprehensive Diabetes Center. "There's reason to believe it could help identify many of the estimated six million people in the U.S. who have diabetes but don't know it," he adds. The current screening and diagnostic tests measure only the amount of sugar present at the moment that blood sample is taken. Consequently, Saudek says, these tests are accurate only if patients fast for at least 10 hours before the test because glucose concentrations can vary greatly depending on a person's recent meals.

Even then, explains Saudek, the tests miss a significant portion of people who have diabetes or are at high risk to develop the disease since glucose also varies depending on a person's diet and exercise regimen for several days leading up to the blood draw.

"If a patient is scheduled for a physical, he or she may 'tune up' by changing their regimen for a few days and throw off their test results, causing doctors to miss the patient's usual pattern of high blood sugar," he says.

In a consensus statement published in the July Journal of Clinical Endocrinology and Metabolism, Saudek and his colleagues conclude that the HbA1c test should be used as a front-line method for identifying patients with diabetes, especially for those at high risk for the disease. Since the test does not require fasting and isn't affected by short-term changes in diet and exercise, the HbA1c test has significant advantages to current testing methods.

The consensus was reached by a group of diabetologists, pathologists and internists seeking to improve detection methods because of the serious consequences of untreated diabetes for patients and public health. They met recently in Chicago with financial support from Metrika Inc., a major manufacturer of diabetes testing equipment. The panel deliberations and manuscript preparation were made independently of the sponsor, according to its members.

After reviewing relevant published studies and available tests, the national panel recommended that individuals who score at least 6 percent on an HbA1c test may have or be at risk for diabetes and should be tracked with additional glucose or HbA1c tests. Those who score between 6.5 percent or above, if confirmed, should be considered to have diabetes.

"This is a first step towards changing medical practice," notes Saudek, and "could greatly enhance how well we're able to identify people with diabetes."

Others who contributed to the consensus statement include William H. Herman of the University of Michigan School of Medicine, David B. Sacks of Brigham & Women's Hospital and Harvard Medical School, Richard M. Bergenstal of the International Diabetes Center, David Edelman of Durham Veterans Administration Medical Center and Duke University, and Mayer B. Davidson of Charles R. Drew University.