In Focus: Dr. Clara Thore

Who: Clara R. Thore, Ph.D., Computer Imaging Specialist

Where she works: The Microvascular Research Lab, Department of Diagnostic Radiology, Wake Forest University School of Medicine , Winston-Salem, North Carolina

Research focus: Microvascular changes in the brain in diseases of aging, such as vascular dementia, leukoaraiosis, and Alzheimer’s disease.

MBF Bioscience software used: Stereo Investigator

Research methods at a glance: Dr. Thore and her fellow researchers have come a long way from their early studies involving scanning AP stained sections on a flatbed scanner to measure vessel density. Today, they use stereological methods, which provide more accurate data and take less time.

What she does: Dr. Thore studies the brain’s tiniest blood vessels. She examines human autopsy material and highly sensitive archival tissues for her research on Alzheimer’s disease, vascular dementia, and other diseases of aging.

At her lab, The Brain Microvascular Pathology Laboratory, she and her colleagues use Stereo Investigator to quantitate vascular densities in the human brain and the brains of experimental animals. One hundred-micrometer-thick sections of celloidin-embedded tissue blocks with arteries, arterioles, and capillaries marked with AP staining provide Dr. Thore with a 3D view of her subject. By implementing stereology, immunohistochemistry, and confocal microscopy techniques, she studies changes to the cerebral microvascular system.

Previously, Dr. Thore and her team measured vessel density by scanning the AP stained sections on a flatbed scanner, which she said provided crude area fraction data. They then captured digital images from sections and used algorithms to process the images to binary in order to quantitate vessel density as area fraction. “The image processing introduced variance, was time consuming, and did not account for the depth of the captured field,” she explained. Dr. Thore and her colleagues began using stereological methods, which they found avoided these problems by providing random systematic sampling.

“The installation of the Stereo Investigator system by MBF Biosciences has made a huge difference in our quantitative approach,” said Dr. Thore. “By using the built-in Stereo Investigator Space Balls probe, we no longer have to be concerned with the directionality of vessels in our sections. Stereological quantization is done real-time, which has decreased the time needed per specimen and allowed us to increase the number of areas and slides sampled.”

“In Focus” is a new series that spotlights scientists who use MBF Bioscience products in their work. Thank you Dr. Clara Thore for participating.

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Stereo Investigator Aids in Researching Familial Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia. Most cases occur in people over 65, and are not genetically inherited. Roughly five percent of Alzheimer’s patients suffer from familial Alzheimer’s disease (FAD), an uncommon form that tends to strike sooner, and is related to a genetic predisposition – most commonly, a mutation in the presenilin 1 gene (PS1).

A recent study, led by Dr. Miguel A. Gama Sosa of the Mount Sinai School of Medicine in New York, shows that the mutated PS1 gene contributes to the vascular pathology of familial Alzheimer’s disease.

During the course of their research, Dr. Gama Sosa’s team used Stereo Investigator for the stereologic analyses of transgenic mouse brains.

“We quantified the density, area and length of the vasculature in the hippocampus of mice that express a mutation associated with familial Alzheimer’s disease,” explained coauthor Dr. Gregory A. Elder of the James J. Peters Veterans Affairs Medical Center in the Bronx.

“We found [Stereo Investigator] easy to use and adaptable to the requirements of the study,” he added.

Read “Age-Related Vascular Pathology in Transgenic Mice Expressing Presenilin 1-Associated Familial Alzheimer’s Disease Mutations” at the American Journal of Pathology.

{Image: Anti collagen IV-peroxidase staining of the hippocampal vasculature of a 26 month-old transgenic mouse expressing a human presenilin 1 (PSEN1) transgene harboring the M146V mutation associated with familial Alzheimer’s disease (FAD). Present are vascular abnormalities including string, tortuous and double-barreled vessels.  In addition many vessels are irregular with decreased diameters. – Courtesy of Miguel Gama-Sosa Ph.D.}

Miguel A. Gama Sosa, Rita De Gasperi, Anne B. Rocher, Athena Ching-Jung Wang,  William G.M. Janssen, Tony Flores, Gissel M. Perez, James Schmeidler, Dara L. Dickstein, Patrick R. Hof, and Gregory A. Elder (2010), “Age-Related Vascular Pathology in Transgenic Mice Expressing Presenilin 1-Associated Familial Alzheimer’s Disease Mutations.” American Journal of Pathology, 176:353-368

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