Project: Research project

Project Details


Head injury is still a leading cause of death and disability despite the
implementation of aggressive methods of evaluation and treatment. To
further improve outcome, effort must now be directed at the basic
pathophysiologic processes involved. This project seeks to elucidate the
pathophysiology of two secondary insults associated with severe head injury
that are linked to poor outcome: 1. Cerebral ischemia, early (within the first 6 hours) after injury, and
focal ischemia in later stages, and 2. The role of increased cerebral blood volume (CBV) in increasing
intracranial pressure (ICP) or "brain stiffness". To date, only a trend
suggesting that ischemia occurs early after injury has been found, as
measurements with 133Xe made in the Intensive Care Unit could not be
performed early enough to confirm this suspicion. Accordingly, we propose
to measure cerebral blood flow (CBF) as early as possible, using the stable
Xenon enhanced CT technique, during the initial diagnostic CT scan of the
patient. To investigate ongoing (focal) ischemia, follow-up Xe-CT CBF
studies will be done on subsequent days. Regional CBF so obtained, will be
related to clinical condition (GCS), CT findings, and outcome. Similar to the problems associated with early CBF studies, determinations
of CBV in both normal and head-injured patients also have been cumbersome
to date, but a recently developed technique enables fast measurement of CBV
during the initial CT scan and at any ensuing CT scan. Following
measurement of CBF with the stable Xenon CT method, mean transit time (MTT)
and CBV will be determined in the same session, using dynamic CT scanning
following an i.v. bolus of iodine contrast. CBV will be correlated with
ICP and a measure of brain stiffness, the pressure-volume-index (PVI).
Additionally, in the same patient population considered above, the
influence of vascular factors upon ICP and PVI will be investigated by
correlating responses of these parameters to blood pressure changes in
patients with intact or defective autoregulation of CBF. The latter will
be determined in the Intensive Care Unit by repeated measurements of CBF,
using the 133Xe-method, and CMRO2, during manipulations of blood pressure. The successful conduct of this study will provide important information in
an area for which little data exists. More importantly, the results of
these investigations should allow for the determination of those patients
who will benefit from therapies to prevent ischemia (e.g. by induced
hypertension, or mannitol therapy), while understanding of the
pathophysiology of increased ICP and brain stiffness will lead to more
rational therapy aimed at either reduce brain edema or cerebral vascular
engorgement. We feel confident, that these improved treatment modalities
will eventually contribute to better outcome.
Effective start/end date9/30/919/29/96


  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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