This study examines the issue of """"""""silent"""""""" strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including brain atrophy and cognitive decline. It addresses the question of the role of carotid emboli in """"""""silent"""""""" stroke and their cognitive sequelae. The study uses human carotid endarterectomy patients to study three specific aims. The first uses ultrasound to relate plaque elasticity and its development of mechanical strain features with pulsation and the histopathophysiology of the plaque for ulcer, hemorrhage and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The second examines ultrasound detected elasticity strain features in the plaques and the presence of transcranial Doppler TCD detectable microemboli. The third looks at ultrasound strain deficits, microemboli, cognitive decline and brain MRI evidence of focal and generalized atrophy. Understanding the structural plaque abnormalities, which render a carotid plaque mechanically unstable and at risk of embolization will demonstrate a pathophysiologic mechanism in individuals who are likely to suffer not only classic episodic major strokes, but also functional progressive decline from the contribution of microemboli to cerebral """"""""silent"""""""" stroke and cognitive decline.

Public Health Relevance

Cerebrovascular disease remains a major health problem with increasing impact on an aging population. Studies suggest that clinical and """"""""silent"""""""" stroke affects 11 million Americans per year. Vascular aging from atherosclerosis is a major contributor to this problem. For this reason, we propose a study of carotid atherosclerosis developing novel markers for carotid plaque instability which may result in the presence of multiple microemboli, which in turn may contribute to increased symptomatology, both classic strokes, as well as, cognitive decline. If successful, this study will greatly increase our understanding of the pathophysiology of symptoms from atherosclerosis, as well as, lead to the development of potential new measures to detect this disorder noninvasively.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS064034-04
Application #
8416383
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Koenig, James I
Project Start
2010-03-15
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
4
Fiscal Year
2013
Total Cost
$300,784
Indirect Cost
$93,912
Name
University of Wisconsin Madison
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Steffel, Catherine N; Brown, Roger; Korcarz, Claudia E et al. (2018) Influence of Ultrasound System and Gain on Grayscale Median Values. J Ultrasound Med :
Dempsey, Robert J; Varghese, Tomy; Jackson, Daren C et al. (2018) Carotid atherosclerotic plaque instability and cognition determined by ultrasound-measured plaque strain in asymptomatic patients with significant stenosis. J Neurosurg 128:111-119
Mitchell, Carol C; Stein, James H; Cook, Thomas D et al. (2017) Histopathologic Validation of Grayscale Carotid Plaque Characteristics Related to Plaque Vulnerability. Ultrasound Med Biol 43:129-137
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Meshram, N H; Varghese, T; Mitchell, C C et al. (2017) Quantification of carotid artery plaque stability with multiple region of interest based ultrasound strain indices and relationship with cognition. Phys Med Biol 62:6341-6360
Garcia-Ramos, Camille; Bobholz, Sam; Dabbs, Kevin et al. (2017) Brain structure and organization five decades after childhood onset epilepsy. Hum Brain Mapp 38:3289-3299
Mitchell, Carol C; Wilbrand, Stephanie M; Kundu, Bornali et al. (2017) Transcranial Doppler and Microemboli Detection: Relationships to Symptomatic Status and Histopathology Findings. Ultrasound Med Biol 43:1861-1867
Jackson, Daren C; Sandoval-Garcia, Carolina; Rocque, Brandon G et al. (2016) Cognitive Deficits in Symptomatic and Asymptomatic Carotid Endarterectomy Surgical Candidates. Arch Clin Neuropsychol 31:1-7

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