Biomedical Engineering Reference
In-Depth Information
MCA
X
MCA
MCA
CW
CW
ICA
ECA
ICA
BA
ECA
BA
(a)
(b)
CBF
ADC
R
2
FIGURE 7.5
Disease phenotyping in rodent model of human embolic stroke. (a) Cerebral ischemia is induced
by permanent transient occlusion of a brain artery, for example, the middle cerebral artery (MCA). The occlu-
sion site is indicated by a cross. As a result, an infarct will develop that occupies large areas of the MCA
irrigation territory. The MRI angiogram of a rat brain (top right) demonstrates the absence of blood l ow in
the left MCA of the animal (yellow arrow). Abbreviations indicate external (ECA) and internal carotid artery
(ICA), basilar artery (BA), and Circle of Willis (CW). (b) The tissue damage is rel ected by changes of various
MRI parameters. The perfusion values (CBF) are dramatically decreased in the affected territory leading to
oxidative stress, the apparent water diffusion coefi cient (ADC) decreases due to cellular swelling caused by
failing membrane pumps, and later the
R
2
relaxation rate decreases due to the formation of a vasogenic edema.
All MRI images have been recorded 24 h following MCA occlusion.
reversible. There is evidence that these early ischemia markers (ADC, CBF) are of predictive value
with regard to the i nal infarct volume.
A word of caution: the identii cation of structural damage is based on the deviation of MRI
parameters from “normality.” This procedure is to some extent arbitrary: CNR depends on multiple
factors such as the general signal-to-noise ratio of the image and the morphological heterogeneity of
the corresponding brain area. This may limit the accuracy of the evaluation.
The primary objective of stroke therapy is not to reduce infarct volume but to improve the clini-
cal outcome for the patient, i.e., to preserve/restore brain functionality. While several cytoprotective
therapy strategies have been shown to reduce infarct volume in animal models of focal cerebral
ischemia, it remains to be shown that regions spared from becoming infarcted are in fact functional.
Studies in rat focal cerebral ischemia revealed functional recovery only in a fraction of the animals,
despite the fact that all animals displayed similar locations and volumes of infarction (Figure 7.6).
Obviously, structural integrity is a necessary yet not a sufi cient prerequisite for functional integrity.
The different functional responses have been attributed to differences in CBF values in the cytopro-
tected territory. The validity of the biomarker 'infarct volume' has to be questioned and it is strongly
recommended to combine structural outcome information with a functional correlate.
In view of the difi culties in treatment of acute stroke, emphasis is currently shifting toward ther-
apy concepts targeting processes in the postacute phase such as inl ammation or aimed at inducing
neuroregeneration. For example, it has been shown that administration of stem cells improves
behavioral outcome in rat stroke models. In this context, imaging has been used to monitor the
