Unilateral Hemispheric Proliferation of Ivy Sign on Fluid-Attenuated Inversion Recovery Images in Moyamoya Disease Correlates Highly with Ipsilateral Hemispheric Decrease of Cerebrovascular Reserve

MR Imaging and MRA.

The routine MR imaging protocol for Moyamoya disease includes FLAIR and MRA images. Moyamoya disease was diagnosed in all patients with use of MRA. Postoperative MR imaging follow-up (average, 10.1 months) was performed for all surgically treated patients. MR imaging was performed with a 3T MR unit (Trio; Siemens Medical Systems, Erlangen, Germany). FLAIR imaging was obtained with a fast FLAIR sequence with a TR of 9000 ms, an effective TE of 86 ms, an inversion time of 2500 ms, a bandwidth of 241 Hz/pixel, and a flip angle of 150°. Image thickness, gap, and matrix for all sequences were 6.0 mm, 1.2 mm, and 384 × 372 pixels, respectively. A 3D time-of-flight MRA was obtained with a TR of 22 ms, an TE of 3.1 ms, a bandwidth of 250 Hz/pixels, and a flip angle of 18°. Voxel size was 0.52 × 0.52 × 0.8 mm, and acquisition matrix was 384 × 320.

An ivy sign on a FLAIR image was defined as a continuous linear or punctate leptomeningeal high signal intensity along the cortical sulci and subarachnoid space. Two neuroradiologists retrospectively reviewed MR images for the ivy sign on FLAIR images and MRA images. We defined the hemispheres as ivy unsymmetric when the proliferative difference of ivy signs on FLAIR images was observed between both hemispheres in each patient. This applies to the patient with no ivy proliferation in the contralateral hemisphere. We defined the hemispheres as ivy symmetric when a symmetric ivy distribution was observed in both hemispheres (Fig 1A). We also defined the ivy-dominant hemisphere as IDH and ivy less-dominant hemisphere as ILDH in the patients with an unsymmetric ivy sign. The relative proliferative differences of ivy signs on FLAIR images between hemispheres in each patient was rated as “minimal” (Fig 1B), “moderate” (Fig 1C), or “marked” (Fig 1D). Minimal proliferation indicating subtle and equivocal high signal intensity along the cortical sulci was seen dominantly in either hemisphere, whereas marked proliferation indicating obvious linear and punctate high signal intensity was encountered dominantly in either hemisphere.

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Fig 1.

The proliferative differences of ivy signs on FLAIR images between both hemispheres in each patient was rated as minimal, moderate, or marked. A, Symmetric ivy distribution. We defined the hemispheres as ivy symmetric when a symmetric ivy distribution was observed in both hemispheres. B, Minimal ivy proliferation along the cortical sulci dominantly in the right frontal lobe (dotted circle). C, moderate ivy dominance in the right hemisphere (dotted circle). D, Marked ivy distribution in the left hemisphere (dotted circle).

The correlation between hemispheric ivy proliferation and MRA images was studied according to the MRA grading system.^3,4 MRA scores of IDH and ILDH were compared. MRA scores were based on the severity of occlusive changes of the internal carotid artery, the horizontal portion of the middle cerebral artery (MCA), the anterior and the posterior cerebral arteries (ACAs and PCAs), and signals of the distal branches of these arteries. Total points ranged from 0 (normal) to 10 (most severe). Four stages on the basis of this novel MRA score correlated well with Suzuki stages, with high sensitivity and specificity (Table 1).³ The correlation between ivy proliferation and MRA stage was examined in each patient.

Analysis of circulation time in angiographic examination.

For 16 patients, we performed cerebral angiography using the Seldinger method and a digital subtraction radiographic angiographic system (Axion Artis; Siemens). The circulation time was determined by a consensus of 2 authors (M.K., T.N.) observing a serial display system. We estimated circulation time by measuring the interval between the time at which the contrast medium filled the siphon portion of the internal carotid artery and the time at which the capillary stain reached its maximal attenuation.⁵ This interval was defined as the regional arteriocapillary circulation time (rACCT) and was evaluated in the bilateral MCA regions of each patient. The ratio of rACCT in IDH to ILDH in patients with an unsymmetric ivy sign was compared with the ratio of the rACCT in the right to left hemispheres in patients with a symmetric ivy sign.

Technique of SPECT.

SPECT scanner MULTISPECT3 (Siemens) and image processor ICONP (Siemens) were used. The collimator used was a low-energy, ultra-high resolution, fan-beam collimator (225 cpm/μCi). Conditions for acquisition were as follows: 20-minute acquisition (40 s/90 steps, 3°step, step-and-shoot method), matrix of 128 × 128 (2.89-mm/pixel), and radius of rotation of 13.9 cm. A filtered backprojection method with a Butterworth filter was used to reconstruct images from 20-minute data. As a 3D postfilter, a low-pass filter (cutoff value, 0.3 cycle/cm; order, 5.0) was used. Two SPECT images were summated to obtain a section thickness of 5.78 mm.

All patients underwent 2 SPECT sessions: a basal study and an ACZ-challenged study. The patients were permitted to rest in a quiet, dimly lit room and were intravenously (IV) injected with ¹²³I-N-isopropyl-p-iodoamphetamine (¹²³I-IMP). We obtained basal images first after injecting the radiotracer. Consecutively, on the same day for semiquantitative SPECT or several days later (3–5 days) for quantitative SPECT, the patients were placed in the same environment as that of the first session and then were IV injected with 1 g of ACZ (Diamox; Lederle Lab Division, Pearl River, NY) during a period of 1 minute. Fifteen minutes later, the patients were injected with ¹²³I-IMP, and the ACZ-challenged images were obtained in the same manner as in the basal study.

Quantitative Estimation of Vascular Reserve and Stage II Area.

In 13 patients including 8 with unsymmetric ivy signs and 5 with ivy symmetric signs, both regional cerebral blood flow (rCBF) and vascular reserve were quantified by autoradiographic processing a single SPECT scan with a 1-point arterial blood sample (IMP-ARG method).⁶ At 10 minutes after beginning ¹²³I-IMP (166.5 MBq) infusion, 1 arterial blood sample was taken to calibrate the previously determined standard input function, and its whole-blood radioactivity concentration was counted with a well counter that had been cross-calibrated with the SPECT scanner. A single SPECT scan was performed at a midscan time of 10 minutes after arterial blood sampling. Basal images were obtained 35 minutes after injecting the radiotracer. In a 2-compartment analysis of ¹²³I-IMP, distribution volume, the ratio of influx constant and efflux constant can be set to a constant value (41.2 mL/mL). rCBF maps were calculated pixel by pixel from single SPECT data, and standard input function was calibrated with a 1-point arterial blood sample.⁶ We also obtained Diamox-activated rCBF maps using the same methods as in the basal study several days later (3–5 days). To objectively classify the severity of hemodynamic ischemia according to the Japanese Extracranial-Intracranial Bypass Trial (JET) study protocol of patients with intracranial occlusive disease,⁷ we performed a quantitative analysis using 3D stereotactic surface projections analytical software (3D-SSP; Nihon Mediphysics, Tokyo, Japan) and stereotactic extraction estimation display software (SEE-JET; Nihon Mediphysics).⁸ This method provides quantitative information and 3D displays of the CBF at rest and after Diamox challenge, vascular reserve, and severity of hemodynamic brain ischemia. Regional vascular reserve was defined as the ratio of the difference between Diamox-activated rCBF and resting rCBF to resting rCBF [(Diamox-activated rCBF/resting rCBF-1) ×100(%)]. Resting rCBF, Diamox-activated rCBF, and regional vascular reserve of bilateral ACA, MCA, and PCA distributions were evaluated at the hemispheres. The severity of hemodynamic brain ischemia was classified into the 3 stages: stage 0 (resting CBF > 15 mL/100 g/min and vascular reserve > 30%), stage I [34 mL/100 g/min (80% of normal CBF) > resting CBF > 15 mL/100 g/min and 30% > vascular reserve > 10%], and stage II (34 mL/100 g/min > resting CBF > 15 mL/100 g/min and 10% > vascular reserve > −30%).^7,8 Finally, the proportion of stage II area to hemisphere (ACA and MCA territories) and mean vascular reserves in hemisphere were compared for IDH and ILDH in patients with an unsymmetric ivy sign and right and left hemispheres in patients with a symmetric ivy sign.

Semiquantitative Estimation of Vascular Reserve.

In 21 patients including 14 with ivy unsymmetric sign and 7 with ivy symmetric sign, the 1-day method for IMP SPECT studies at rest and after ACZ challenge was performed.⁹ Two doses of 111 MBq ¹²³I-IMP were IV injected for 1 minute, one at the beginning and the other at 30 minutes after the first IMP injection. ACZ (1 g) was slowly IV injected for 1 minute, starting 15 minutes before the end of the initial scan. Among the sections obtained in the basal SPECT study, 1 tomographic plane located 50 to 75 mm above and parallel to the orbitomeatal line, and showing the most prominent contrast in the ACA and MCA territories, was selected for each patient, and the regions of interest (ROIs) were placed directly on each SPECT image. ROIs were placed in the region where infarction was not present on MR imaging. On each SPECT image, mirror-image ROIs were also placed in the corresponding region on the contralateral side. Identical ROIs were analyzed in each subject for SPECT studies. The ratio of the quantitative radioactivity count obtained from the ROI on the IDH of the MCA territories to that obtained from the ROI on the ILDH was calculated by asymmetry index (AI: mean count on the IDH/mean count on the ILDH) in patients with an ivy unsymmetric sign.⁵ If the dominancy of the ivy side was not determined in a patient, the AI was calculated as the quantitative radioactivity count obtained from the ROIs on the right side of the ACA and MCA territories to that obtained from the left side. For the ACZ-challenged SPECT study, a section was selected at the same level as that selected in the basal study, and the AI was calculated with use of the same methods as in the basal study. The proportion of ACZ-challenged AI to basal AI was then defined as the regional reactivity index (rRI). Finally, mean RIs of the ACA and MCA territories were compared between the patients with an unsymmetric ivy sign and patients with a symmetric ivy sign.