New Imaging to Measure White Matter Damage and Inflammation in Alzheimer’s

Yong Wang, PhD
Washington University School of Medicine (St. Louis, MO)

Collaborators

Yi Su, PhD
Washington University (St. Louis, MO)
Jinbin Xu, PhD
Washington University (St. Louis, MO)
Year Awarded:
2017
Grant Duration:
July 1, 2017 to June 30, 2020
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2017330S
Award Type:
Standard
Award Region:
US Midwestern
Yong Wang, PhD

PET-MRI Imaging of White Matter Damages and Inflammation in AD

Summary

Our new PET-MRI [positron emission tomography–magnetic resonance imaging] method takes pictures of the brain in elderly people. Whereas these PET-MRI images have commonly been used to identify tumors or strokes in patients, we have found a new way to use PET-MRI to measure the brain’s injury and immune response. We have found this imaging method to be very useful in patients with multiple sclerosis, and now we are able to use it in patients who have Alzheimer’s disease (AD), in order to get a sense of the problems that might be developing in their brain before memory problems occur. We hope that our new method also will be useful in clinical trials testing new drugs for early intervention with AD.  

Details

Our goal is to use a new imaging system to monitor damage caused by AD to the brain region that contains the insulated axons (analogous to cables) connecting the neuron cell bodies (analogous to the central processing unit of a computer). In the first part of our project, we will test the hypothesis that our imaging system, which combines PET and a new form of MRI that I invented called diffusion basis spectrum imaging (DBSI), can reliably detect and measure the severity of white matter damage and inflammation. Additionally, we hypothesize that PET/DBSI can accurately reflect a patient’s cognitive decline and disease progression. We will perform this investigation in people aging normally as well as those at different stages of AD. In the second part of the project, we will define, at the microscopic level, the cellular features that the PET/DBSI system detects. We will perform PET/DBSI on 8 whole brain autopsy samples (2 males with AD, 2 females with AD, 2 males with normal aging, and 2 females with normal aging). We will then perform microscopy studies on the same brains and align the two sets of images.

This project has two innovative features that set it apart from other AD imaging studies. We will be the first researchers to integrate PET and DBSI into a single scan to detect white matter damage and inflammation. Additionally, through the Washington University Knight Alzheimer's Disease Research Center, we are fortunate to have access to a unique group of elderly people with normal cognition (normal aging and those who will, but have not yet, developed AD symptoms) and abnormal cognition (symptomatic AD) that have been studied for many years.

Our study will benefit AD researchers by providing them with a new tool, PET /DBSI imaging, to image white matter damage and inflammation in patients before or after they develop AD symptoms. Our imaging system offers additional benefit to patients by allowing researchers to conduct clinical studies of drugs that might slow or reverse white matter damage, and thus slow or prevent the development of AD symptoms.

About the Researcher

Dr. Yong Wang obtained his undergraduate degree in electrical engineering from Xi’an Jiaotong University in China. He then did his graduate work in the Department of Biomedical Engineering at Washington University in St. Louis, MO, USA. His PhD work focused on developing and applying electrocardiographic imaging to study cardiac arrhythmia and abnormal heart contractions. Driven by his intense interest in imaging and neuroscience, Dr. Wang switched gears and devoted his postdoctoral training to gaining expertise in neuroscience and radiology. During this time, Dr. Wang invented a novel MRI approach called diffusion basis spectrum imaging (DBSI). He patented DBSI and published papers demonstrating that it could be used to specifically measure and characterize multiple types of white matter microstructural changes. He also showed that DBSI could be used to examine the development of white matter inflammation in patients with neurodegenerative diseases and in animal models of these diseases. As a postdoc and junior faculty member, Dr. Wang collaborated with radiologists and neurologists at Washington University to develop the PET/DBSI system that he is using in his work funded by BrightFocus. Dr. Wang is an assistant professor at Washington University with appointments in Obstetrics and Gynecology, Radiology, and Biomedical Engineering. In addition to his work on AD, Dr. Wang is using his DBSI method and his skills in electrical imaging to ask questions that span the lifespan from the womb to old age.

Personal Story

While growing up in China, I was amazed by the complexity and power of modern integrated electrical circuits through which sophisticated information can be precisely processed, vividly displayed, and instantaneously transmitted. Thus, I received my undergraduate degree in electrical engineering from Xi’an Jiaotong University. In 2002, I moved to the United States for my graduate study in biomedical engineering at Washington University in St. Louis. For the first time, I was intensively exposed to human pathophysiology, revealing to me that the living body is much more complicated and interesting than any integrated circuits.

Unlike man-made devices, living organs, such as the heart and the brain, have the amazing ability to resist damage, compensate for injuries when it occurs, and repair themselves. These complicated self-protection processes are critical for the body to function properly for many decades. During my graduate work, I became convinced that by gaining a better understanding of how the body reacts to aging and repairs itself after injury, we will be able to greatly improve our quality of life, especially given our aging population. After all, it is the healthy body that will allow us to truly enjoy the fruits of the advances of modern technology.

To combine my conviction and scientific interests, I trained as a postdoctoral fellow in the field of neuroimaging of central nervous system diseases, especially neurodegenerative diseases such as AD. In particular, I seek to determine how damage to white matter contributes to AD pathology and development of symptoms. Although it is well known that white matter damage and inflammation are associated with cognitive dysfunction and AD etiology, currently available imaging techniques are insufficient to sensitively and specifically image the white matter damage in AD patients. The generous support from the BrightFocus Foundation will enable my lab to carefully validate a novel imaging technique to, for the first time, noninvasively detect white matter damage and define its role in cognitive decline in AD patients. In the long term, we will be able to use this imaging system to determine how the human brain responds to disease-modifying treatments. I am very thankful to the BrightFocus donors whose support enables researchers like me to pursue innovative ideas that will one day allow us to predict and prevent the development of AD symptoms in patients.

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