Project: Research project

Project Details


We propose to investigate several closely interrelated research issues in
human cerebrovascular disease, using emission-tomographic strategies and
short-lived radiolabeled tracer substances (chiefly (15)0-water,
(15)O-oxygen, and (11)C-carbon monoxide) to characterize local metabolism
and hemodynamics. (1) Patients with asymptomatic extracranial carotid
artery lesions are studied to determine the hemodynamic impediment
associated with graded stenosis. The chief hypothesis is that diameter
stenoses above 75% induce local hemodynamic alterations, consisting
initially of increased local blood volume (lCBV) with normal blood flow
(lCBF), and that decreased local oxygen utilization (lCMR02) correlates
with severe vascular stenosis or occlusion. (2) Patients with recent
transient cerebral ischemic attacks are studied to define the frequency and
extent of residual postischemic impairments of lCBF and lCMRO2.
Standardized sensorimotor activation tasks are employed to determine
whether the post-TIA state is associated with impaired hemodynamic and
metabolic activation as compared to age-matched non-TIA controls. (3) We
intend to assess the capability of emission tomography in monitoring
responsiveness to acutely administered therapeutic agents by studying
patients with recent completed thromboembolic infarction before and after
acute hemodilution with low molecular weight dextran. We seek to determine
whether this treatment improves local flow and oxygen extraction in and
adjacent to the ischemic focus. (4) A sequential dual-tracer technique is
used to quantitate local blood-brain barrier permeability to
diffusion-limited radiotracers (such as (11)C-antipyrine) in patients with
recent completed thromboembolic hemispheric strokes; barrier alterations
are correlated with local flow patterns and with computed-tomographic
appearances of infarct and adema in central and marginal zones of cerebral
infarcts of different ages. (5) Concurrently, we propose to implement and
validate a mathematical strategy for the simultaneous determination of
local blood flow and local brain:brain partition coefficient. In addition,
we propose to improve the existing mathematical model of oxygen extraction
fraction by reformulating the model in terms of linear differential
equations amenable to solution by the technique of dynamic approximation,
and by explicitly incorporating radioactive decay.
Effective start/end date12/1/845/31/90


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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