In patients with moyamoya disease, long-standing hemodynamic ischemia can lasted in their anterior circulation. Atrophic changes of frontal lobe were occasionally observed in CT or MRI. However, frontal cortical neuron damages involving incomplete brain infarc- tion have not been estimated until IMZ-SPECT became available for clinical use. On the other hand, hemodynamic cerebral ischemia can be stratified by both resting and acetazol- amide-activated CBF-SPECT quantification. The stage of hemodynamic cerebral ischemia can be stratified as follows [15] : Stage 0: cerebrovascular reserve [(acetazolamide-activated CBF-resting CBF)/resting CBF × 100%] is preserved more than 30%; Stage I: cerebrovas- cular reserve is reduced from 10 to 30%, or cerebrovascular reserve is reduced less than 10% and resting CBF is preserved more than 80% of normal mean CBF; Stage II: cerebro- vascular reserve is reduced less than 10% and resting CBF is reduced less than 80% of normal mean CBF.
Based on the development of these functional neuroimagings, relationship between long- standing hemodynamic ischemia and the occurrence of incomplete brain infarction in patients with moyamoya disease was studied by stratification of hemodynamic cerebral ischemia using quantified CBF-SPECT and central BZ receptor mapping using IMZ-SPECT. Ten patients with moyamoya disease (seven with TIA or infarction, three with ICH) were enrolled in this study. The stage of hemodynamic ischemia (0–II) was estimated by CBF-SPECT quantification using the 123 I-IMP-ARG method. The stage of hemodynamic ischemia in the cerebral cortex was estimated using stereotactic extraction estimation (SEE) analysis [16] (see
“Overview” chapter). In SEE analysis, resting and acetazolamide-activated CBF-SPECT are stereotactically and quantitatively conversed to brain surface CBF. The conversions are per- formed pixel by pixel on the frame of Talairach’s standard brain reference which has been utilized in 3D-SSP analysis. Then, stereotactic estimations of cerebrovascular reserve and stereotactic stratification of hemodynamic cerebral ischemia (Stages 0–II) [15] can be com- pleted pixel by pixel on the same frame (Fig. 3 ). On the other hand, incomplete brain infarc- tion was defined as a significant reduction of BZ receptor density by 3D-SSP analysis of IMZ-SPECT. Delayed image 3-h after tracer injection was dealt as equivalent map to BZ receptor density.
As a study result, the areas of incomplete brain infarction were displayed on 3D-SSP by the cluster of pixels which consisted of Z -score value more than 2 SD. Incomplete brain infarction defined by 3D-SSP analysis of IMZ-SPECT was observed not only in Stage II ischemic area but also in part of Stage I ischemic area (Figs. 4 and 5 ). In cases with ICH, selective loss of cortical neuron was occasionally observed by undercutting of cortex (white matter lesions).
In conclusion, long-standing hemodynamic ischemia in patients with moyamoya disease can result in selective loss of cortical neuron (incomplete brain infarction). Cortical neuron can be damaged by long-standing hemodynamic ischemia, even though the degree of hemodynamic ischemia has been mildly reduced (Fig. 6 ). Statistical imaging analysis of incomplete brain infarction in moyamoya disease could be valuable for assessing the prognosis of surgical revascularization and the evidence of higher brain dysfunction.
193 Iomazenil SPECT (BZP-Receptor)
Fig. 4 A 30-year-old female, suffered from TIA such as the left hemiparesis. After the bilateral EC-IC bypass surgery was performed, no TIA episode was noted. However, a wide decrease of cerebrovascular reserve and a partial Stage II ischemia was persisted in bilateral frontal lobes using SEE analysis. Incomplete brain infarction defined by 3D-SSP analysis of IMZ-SPECT ( Z -score > 2) was observed in the right high frontal lobe corresponding to persisted Stage II ischemia
Fig. 2 ( Upper 2 rows ) A serial change of IMZ distribution after intravenous tracer injection was demonstrated in a patient with the left MCA embolism. The fast-in, fast-out of the tracer distribution was observed in the left cerebellar cortex, the slow-in, slow-out of the tracer distribution was observed in the right cerebellar cortex. Three hours after tracer injection, pseudo-equilibrium state was obtained on IMZ-3 h image. ( Lower row ) IMZ-K1 and IMZ- V d images were calculated using two-compartment model. The binding potential of IMZ in relative units corresponding to IMZ- V d images is practically proportional to the tracer distribution in relative units on IMZ-3 h image. Correlation between asymmetry index (AI) of IMZ- V d ( Y ) and AI of IMZ-3 h ( X ): Y = 0.971 X + 2.193 ( r 2 = 0.995) (AI; circle ROI on affected side/circle ROI on unaffected side (%); size of circle ROI = 10 pixels) Fig. 3 Hemodynamic cerebral ischemia could be quantitatively and stereotactically assessed using stereotactic extraction estimation (SEE) analysis. ( Left ) From the upper low, brain surface images of standardized brain MRI, resting CBF, acetazolamide-activated CBF, cerebrovascular reserve and stage of hemodynamic ischemia are indicated. ( Right ) Stratification of hemodynamic cerebral ischemia using quantified resting and acetazolamide-activated CBF-SPECT. Stages 0–II are defined in the text Fig. 5 A 47-year-old female, suffered from TIA such as the right hemiparesis. After the left EC-IC bypass surgery was performed, severity of hemodynamic cerebral ischemia in the left cerebral hemisphere using SEE analysis was improved form Stage II ischemia to Stage I ischemia. However, incomplete brain infarction defined by 3D-SSP analy- sis of IMZ-SPECT ( Z -score > 2) was observed in the right MCA territory and bilateral frontal pole (estimated as Stage I ischemia) where surgical revascularization was not performed Fig. 7 In a patient with higher brain dysfunctions defined by neuropsychological tests, a partial CBF reduction ( upper row ) and cortical neuron loss ( lower row ) were observed in bilateral medial and lateral frontal lobes. Z -score images were normalized by global hemisphere (GLB) Fig. 8 In a group comparison between patients with higher brain dysfunction and normal database, cortical neuron loss was observed in bilateral medial frontal lobes involving the anterior cingulate cortex ( upper row ). On the other hand, in a group comparison between patients without higher brain dysfunction and normal database, there is no cortical neuron loss in bilateral medial frontal lobes involving the anterior cingulate cortex but cortical neuron loss in the bilateral posterior cingulate cor- tex ( lower row )
194 J. Nakagawara