186 J.C. Paeng and D.S. Lee
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] .
187 Brain Perfusion SPECT
although it is more common in high-flow direct revascularization surgery. The symptoms of HPS include headache, transient neurological deficit, seizure, cerebral edema, and hemorrhage, and so on. Therefore, in cases where acute neurological deficit after revascularization surgery is presented, HPS is considered in addition to sustained or even aggravated hemodynamic impair- ment. Brain perfusion SPECT has been used in postoperative HPS, and has shown the hyper- perfusion status with quantitative or semiquantitative measurements. In some studies, severe hyperperfusion such as about 100% more perfusion than the contralateral side was reported [24] . However, even mild to moderate hyperperfusion by about 10–40% may cause HPS, because vascular reactivity and permeability are impaired in the affected regions [25] . Brain perfusion SPECT is an excellent tool to assess HPS.
Future Perspectives
One of recent trends of development in medial imaging is the fusion of multimodal images between computed tomography (CT), magnetic resonance image (MRI), SPECT, and PET.
Among these, fusion images between structural images (CT or MRI) and functional images (SPECT or PET) are of most interest. Many software fusion methods have been used for more than a decade, and, recently, hardware fusion became available with commercial products of PET/CT and SPECT/CT. Also, PET/MRI is under development and expected to be available within a couple of years. Fusion with optical imaging will be more helpful for surgery because it can visualize perfusion or other specific imaging targets directly in the surgical field.
Neurological disorders including MMD will benefit from these new modalities, and a recent study showed a potential of fusion images in which the recipient for cerebral artery anastomosis surgery was selected by fusion images between MRI and perfusion SPECT [26] .
Another trend in medical imaging is the adoption of molecular imaging, which means imaging for the molecular level affairs. In MMD, very few functional imaging over perfusion imaging have been tried. For example, 123 I-iomazenil SPECT has been tried for the assessment of neuronal loss, in which iomazenil binds to a ubiquitous neuronal receptor of the central benzodiazepine receptor [27] . In the future, such molecular imaging as hypoxia, apoptosis, and angiogenesis imaging are expected to be introduced to clinical fields. At present, several molecular imaging probes have already been developed and tried in preclinical or clinical studies, including 99m Tc-labeled nitroimidazole for hypoxia imaging, 99m Tc-annexin V for apoptosis imaging, and RGD derivatives for angiogenesis imaging. These molecular imaging methods are expected to be helpful in the diagnosis and treatment of MMD patients, as well as in other diseases.
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189
Introduction
123 I-Iomazenil (IMZ) [1] is a specific radioligand for the central benzodiazepine (BZ) receptor that may be useful as an indicator of cortical neuron loss after focal cerebral ischemia using SPECT [2, 3] . The reduction of BZ receptor density in reperfused cortex that remained structurally intact is likely to be the result of injury to only a limited number of neurons (i.e., incomplete brain infarction) [3] . The study of permanent or transient ischemia (lasting 3–6 h) in baboons by Sette et al. [4] , who used 18 F-flumazenil as a BZ receptor ligand and PET, has a more direct relevance to the study of the incomplete brain infarction in reperfused cortex using IMZ-SPECT. They observed a decrease of BZ receptor binding not only in the infracted area but also, albeit to a lesser degree, in the CT-intact opercular cortex overlying the hypodense area. Selective neuronal necrosis with sparing of glia and microvessels is seen after transient occlusion of the MCA in macaque monkey and rats [5, 6] . The extent of ischemic neuronal damage depends on both the magnitude and duration of cerebral ischemia. In the study by Garcia et al. [7] , up to 60 min of MCA occlusion followed by 7 days of survival in rats resulted in neuronal necrosis that involved isolated groups of cortical neurons (i.e., incomplete brain infarction), while no cases of cortical infarction were found. A close correlation existed between the number of necrotic neurons and the severity of the neurological deficits.
Incomplete brain infarction defined by the reduction of central BZ receptor density using IMZ-SPECT had been observed within ischemic penumbra salvaged by restored CBF in the acute stroke [3] and could be occurred within long-term hemodynamic cerebral ischemia such as misery perfusion in the chronic stroke [8] . More recently, the relationship between long-term hemodynamic ischemia and the occurrence of incomplete brain infarction in patients with moyamoya disease was estimated to establish functional neuroimagings of the higher brain dysfunction by IMZ-SPECT.
J. Nakagawara (!)
Department of Neurosurgery , Nakamura Memorial Hospital , South-1, West-14, Chuo-ku , Sapporo 060-8570 , Japan e-mail: [email protected]
Iomazenil SPECT (BZP-Receptor)
Jyoji Nakagawara
B.-K. Cho and T. Tominaga (eds.), Moyamoya Disease Update, DOI 10.1007/978-4-431-99703-0_27, © Springer 2010
190 J. Nakagawara