Physiological Assessment in Stroke Research - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 83

brain microcirculation in healthy and diseased tissue and to follow
changes after the application of drugs (monitoring angiogenesis
and/or arteriogenesis after drug treatment in stroke) or during sub-
lethal global hypoxic preconditioning ( 44 ). Another advantage of
Doppler imaging is that blood fl ow measurements can be performed
through the skull without the need of a cranial window in mice and
young rats. However, adult rats and other small rodents often need
a cranial window to allow for accurate CBF detection and measure-
ment. On the other hand, LDF does not allow the direct measure-
ment of absolute CBF values, but only allows accurate measurements
of changes in CBF, after the induction of focal cerebral ischemia for
example ( 45 ). Another drawback is the diffi culty of controlling the
location of the scanned area because the visualization of the cortex
underneath the laser is obscured; a problem relatively improved by
repeated measuring and signal averaging.
Technique
Appropriately anesthetize the animal

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Expose the skull

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Point the laser beam onto the area corresponding to the infarct

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(in our experiments with a middle cerebral artery occlusion
model, the scanning region has a center point of ML 4.1 mm,
and the four edges of the infarct area are ML +2.9 mm,
−5.3 mm, AP +1.5 mm, and AP −2.0 mm)
Start measurements (we use Periscan system PIM II and

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LDPIwin 2/Perimed AB, Stockholm, Sweden). Adjust your
computer software to make several measurements every time.

5.3. Nuclear Imaging

Many other techniques have been used for measuring cerebral
blood fl ow. Magnetic resonance imaging (MRI) and nuclear imag-
ing (single photon emission computed tomography (SPECT) and
positron emission tomography (PET)) are gaining more attention
especially in clinical settings. Both techniques have also been used
in basic research with animals ( 41 ). However, their use is limited to
specialized centers and not available in every laboratory setting.
The initial investment is very expensive and their operation is time-
consuming and requires technical skills and specialized personnel.
However, MRI and nuclear imaging are expected to be the gold
standard modalities for the future of imaging in the clinical setting
of stroke and other neurologic and non-neurologic diseases.

Another technique used to measure cerebral blood fl ow is based
on the use of microspheres developed by Rudolph AM et al. ( 46 ).
The concept of CBF measurement by microspheres is based on
that microsphere, being slightly larger than brain capillaries, will
block these vessels. Since microspheres distribute in the circulation
in proportion to fl ow, the number of trapped radioactive microspheres

5.4. Microspheres