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which relies on the assumption that rCBF is coupled to neuronal
activity, could be temporarily compromised by the metabolic
uncoupling that occurs following brain injury. Nevertheless, clini-
cal evidence suggests that SPECT can detect areas of damage after
TBI that are invisible to CT and MRI, and that SPECT-detected
abnormalities may be linked to functional outcome ( 26 ). Small
animal SPECT imaging systems are less expensive than other types
of preclinical neuroimaging systems and are commercially available
from several sources (Gamma Medica; Bioscan Inc.).
6. Practical
Considerations for
TBI Neuroimaging
When designing and implementing a neuroimaging study of TBI
in small animals, there are several practical considerations the
researcher should bear in mind. Acquiring high-quality neuroim-
aging data of any type requires the head to be immobilized. Thus,
animals must be kept under general anesthesia for the duration of
the experiment. In some cases, injectable anesthetic may be used,
but inhalation anesthesia (isofl urane) has become the method of
choice in most laboratories because it is fast-acting and easily
adjustable. It is important to note that prolonged anesthesia (either
injectable or inhaled) has the potential to affect metabolism,
pathology, and outcome after experimental TBI. Some anesthetic
agents might confound experimental results through possible
neuroprotective effects. Since anesthesia is required for neuroimaging
data acquisition, we recommend a study design in which control
groups receive the same amount of anesthesia as animals that
undergo TBI and neuroimaging. In some cases, the parameters of
the experimental injury may have to be adjusted to offset the pro-
tective effects of prolonged anesthesia. Recent work suggests that
the injectable anesthetic medetomidine has a lesser effect on neu-
ronal activity than isofl urane and may be preferable for studies of
functional brain activation or cerebral blood fl ow in rodents ( 27 ).
Even with the use of anesthesia, the animal must also be physi-
cally secured within the scanner to minimize image artifact from
small movements from respiration or other sources. Many small
animal imaging systems provide some sort of cradle to support and
immobilize the animal, but many laboratories customize or build
their own. MR-compatible head holders with earbars are also avail-
able and may be incorporated into the support cradle. When an
animal is under general anesthesia inside the scanner, temperature
needs to be modulated to offset anesthesia-related metabolic
depression. Thus, a system for monitoring core temperature and
providing temperature control must also be incorporated into the
support cradle, typically through a thermostatic heating bed that
circulates warm water. After imaging is complete and the animal is
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