Normal Brain Perfusion SPECT
Normal brain perfusion changes according to age. Brain perfusion of a neonate is globally lower, but gradually increases to be even higher than that of an adult until the age of 7 years.
Afterwards, global brain perfusion gradually decreases to be similar to that of an adult at adolescence. Although there are some age-related variations of regional cerebral perfusion, the perfusion patterns are similar between different ages more than 10 years old [13] . In a normal brain perfusion SPECT, high perfusion is observed in the gray matter including basal ganglia and thalami, and especially in the primary visual cortex. Normal brain perfusion SPECT images are demonstrated in Fig. 1 .
4-yr-old Male
46-yr-old Female
Fig. 1 Normal brain perfusion SPECT images of a 4-year-old male and a 46-year-old female MMD patients
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Hemodynamic Changes in MMD
In a normal adult, cerebral perfusion is 70–90 mL/min/100 g in the gray matter, 20–30 mL/
min/100 g in the white matter, and around 50 mL/min/100 g on average. In chronic progressive vascular obstruction, perfusion is preserved until a critical point by the autoregulation of cerebral vascular resistance. In the early phase of vascular obstruction, the autoregulation induces lowering of vascular resistance in response to decreasing cerebral perfusion pressure (CPP).
This compensatory mechanism results in increased CBV, decreased CVR, and preservation of CBF. A further fall in CPP is accompanied with decrease in CBF. However, cerebral metabolic rate of O 2 (CMRO 2 ) and metabolic rate of glucose (CMR glu ) are still preserved by an increase in oxygen extraction fraction (OEF) of brain tissue. A fall of average CBF under 20–25 mL/min/100 g may cause neurologic deficit, which would become irreversible under 10 mL/min/100 g of average CBF.
Most of the above-mentioned hemodynamic parameters can be evaluated noninvasively using SPECT and positron emission tomography (PET). SPECT with radiolabeled red blood cells is used for measurement of CBV. OEF or CMRO 2 can be measured by 15 O–H 2 O and
15 O PET, and CMR glu by 8 F-FDG PET. CBF and CVR are evaluated by brain perfusion SPECT, as described above.
Preoperative Assessment
In MMD, the characteristic hemodynamic change is ‘decreased CVR’ in the brain region subtending the affected cerebral artery, which is demonstrated as aggravated perfusion on acetazolamide-stress SPECT (Fig. 2 ). A basal perfusion study may also show various degrees of decreased radioactivity reflecting hypoperfusion probably coupled with hypometabolism in the region. Ischemic infarct is demonstrated as a defect area in perfusion SPECT (Fig. 3 ), and common in watershed zones. In some cases, brain regions that are functionally connected with
Basal
Stress
Fig. 2 Brain perfusion SPECT images of a typical MMD case (5-year-old male). While basal SPECT shows just subtle perfusion abnormality, stress SPECT demonstrates definite abnormality of CVR in the whole left internal carotid artery territory ( arrow and arrowhead ), with its most severity in the left posterior watershed zone ( arrow )
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Basal Stress
MRI
Fig. 3 Cerebral infarct of a 22-year-old patient with MMD. In the left posterior border zone, large perfusion defect that does not change between stress and rest is observed ( arrow )
the primarily affected area may show hypoperfusion without hemodynamic impairment, which is known as “diaschisis.” This phenomenon results from functional inhibition by neuronal deaf- ferentation from the affected lesion. The region of diaschisis shows preserved vasoreactivity to acetazolamide stress in spite of decreased basal perfusion [14] . Abnormal basal perfusion usually recovers after successful revascularization surgery in the noninfarct area.
Hemodynamic status assessed on acetazolamide-stress SPECT is closely correlated with the manifestations of patients. Decrease in CBF and CVR is more severe in symptomatic MMD patients, and specific symptoms from MMD are related to the specific regions of hemodynamic impairment. Movement disorders such as chorea and dystonia are presented in cases where CBF and CVR are decreased in the striatum [15] . Visual symptoms such as visual field defects are observed in cases where the occipital lobe is involved in hemodynamic impairment [16] . However, the most commonly involved areas are the parietal and frontal areas subtending the middle cerebral artery. The caudate nucleus is often spared by the supply from posterior circulation. In cases where the anterior cerebral artery is affected, the medial frontal area shows deteriorated hemodynamics. As can be expected, however, the occipital lobes subtending posterior circulation are usually spared in MMD, because MMD predominantly affects the internal carotid arteries. However, in cases where the posterior circulation is impaired, more severe ischemia is presented due to loss of the source for collateral supply [17] .
In cerebrovascular diseases, medical treatment is inappropriate in patients with decreased CBF and CVR, and revascularization surgery is recommended [18] . Patients with decreased CVR but with preserved basal CBF may demonstrate marked improvement of ischemic symptoms after revascularization surgery [19] , while postoperative improvement of symptoms is not so marked in patients with preexisting infarct.
Postoperative Assessment
Acetazolamide-stress SPECT is a very useful modality for postoperative assessment of patients, because it is noninvasive, quantitative or semiquantitative, and easy to perform, compared with conventional cerebral angiography. Hemodynamic improvement after revascularization
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surgery is well demonstrated on acetazolamide-stress SPECT (Fig. 4 ). Infrequently, basal CBF has shown temporary increase within several days or a week after surgery reflecting some hyperperfusion, which returns to normal after a while. After successful surgery, CVR usually shows gradual improvement up to several months after surgery.
Postoperative hemodynamic status measured on acetazolamide-stress SPECT after the completion of the surgery on both hemispheres is closely related to further prognosis. In a study on clinical outcome of MMD patients after revascularization surgery, regional CVR status on postoperative SPECT was the most significant predictor for the symptomatic outcome of patients [20] . If a patient’s CVR was still poor after revascularization surgery, prognosis on symptoms or neurologic deficits was also poor. Therefore, additional surgical intervention is recommended if a patient’s hemodynamic status after initial revascularization surgery still shows abnormality [21] .
Acetazolamide-stress SPECT has also been used to evaluate the efficacy of newly introduced surgical techniques. In addition to direct revascularization such as the external to internal carotid bypass surgery, the efficacy of indirect revascularization surgery such as encephalo-duro-arterio-synangiosis and encephalo-galeo-synangiosis (EGS) were verified by comparison of pre- and postoperative acetazolamide-stress SPECT [22, 23] .