Diagnostic Imaging of Higher Brain Dysfunction in Patients With Adult Moyamoya Disease Using Statistical Imaging Analysis for [<sup>123</sup>I]Iomazenil Single Photon Emission Computed Tomography

Abstract

[123I]iomazenil (IMZ) is a specific radioligand for the central benzodiazepine (BZ) receptor that may be useful as a marker of cortical neuron loss after cerebral ischemia using single photon emission computed tomography (SPECT). This study used statistical imaging analysis for IMZ-SPECT to investigate the relationship between higher brain dysfunction and cortical neuron loss in the medial frontal lobes, to establish a confirmatory diagnosis of higher brain dysfunction in patients with adult moyamoya disease. IMZ-SPECT was estimated by three-dimensional stereotactic surface projections (3D-SSP). Cortical neuron loss was analyzed using the stereotactic extraction estimation (SEE) method (level 3: gyrus level) for 3D-SSP Z-score maps (Z-score >2). Extent of pixels with significant reduction of BZ receptor density within the target gyri (i.e. bilateral medial frontal gyri [MFGs] and anterior cingulate gyri [ACGs]) was calculated. In 6 patients with higher brain dysfunction, significant cortical neuron loss was observed in the bilateral MFGs in 4 patients, unilateral MFG in 1 patient, and bilateral ACGs in 2 patients. In 12 patients without higher brain dysfunction, no significant cortical neuron loss was observed in the bilateral MFGs or ACGs, and mild loss was observed in the bilateral MFGs in 2 patients, unilateral MFG in 4 patients, and unilateral ACG in 2 patients. Long-standing mild hemodynamic ischemia in the anterior circulation of patients with adult moyamoya disease could lead to incomplete brain infarction within the medial frontal lobes. Statistical imaging analysis using 3D-SSP and SEE methods for IMZ-SPECT could demonstrate significant cortical neuron loss in the bilateral frontal medial cortices involving MFG and/or ACG which correlate with higher brain dysfunction in patients with adult moyamoya disease.