Masashi Nishihara

Arterial spin-labeling MR imaging in moyamoya disease compared with SPECT imaging.

OBJECTIVE Arterial spin-labeling (ASL) is a noninvasive magnetic resonance (MR) imaging method used to obtain brain perfusion information on various cerebrovascular diseases. We retrospectively compared the use of ASL-MRI and single-photon emission CT (SPECT) imaging to determine absolute cerebral blood flow (CBF) in moyamoya disease. MATERIALS AND METHODS CBF examinations using ASL-MRI on 3-T MRI and SPECT imagings with iodine-123-N-isopropyl-p-iodoamphetamine at resting (rest-IMP) and after acetazolamide challenge (ACZ-IMP) were performed on 12 patients with moyamoya disease (men, 5; women, 7; age range/average (year), 7-66/35.0). The CBF values determined by ASL-MRI (ASL-value), rest-IMP (rest-IMP-value), and ACZ-IMP (ACZ-IMP-value) of cerebral hemispheres (24 sides) were measured with normalized CBF maps created from data of those 3 perfusion imaging methods. Cerebrovascular reactivity (CVR) was calculated as follows: {(ACZ-IMP-value)-(rest-IMP-value)}/(rest-IMP-value)×100 (%). The ASL-value was compared with the rest-IMP-value, ACZ-IMP-value, and CVR. RESULTS The ASL-value, rest-IMP-value, ACZ-IMP-value, and CVR (average±standard deviation) were 26.6±14.8 (mL/100 g/min), 27.5±6.4 (mL/100 g/min), 37.1±13.2 (mL/100 g/min), and 35.9±44.3 (%), respectively. Significant relationships between the ASL-value versus (vs.) the rest-IMP-value (rs=0.500, p<0.05), the ASL-value vs. the ACZ-IMP-value (rs=0.863, p<0.01), and the ASL-value vs. the CVR (rs=0.699, p<0.01) were observed. CONCLUSION Although the ASL-value was lower than the rest-IMP-value, the significant relationship between the ASL-value and the rest-IMP-value may suggest that perfusion imaging by ASL-MRI could be used to recognize the condition of brain perfusion. In particular, the stronger correlation coefficient between the ASL-value and ACZ-IMP-value might suggest that perfusion imaging by ASL-MRI could show the potentially dangerous zone for ischemia.

Distributional Impact of Brain Microbleeds on Global Cognitive Function in Adults Without Neurological Disorder

Background and Purpose— Brain microbleeds (MBs) are considered to be associated with cognitive decline and can be pathologically and topographically classified as cerebral amyloid angiopathy-related (located in lobar regions) and hypertensive microangiopathy-related (located in deep regions). We examined whether different effects on global cognitive function might be seen with different distributions of MBs. Methods— A total of 1279 adults without neurological disorders were studied prospectively. Subjects were divided into 4 groups: without-MBs group; lobar group; deep group; and with in both areas (diffuse group). The Mini-Mental State Examination was administered to determine global cognitive functions, with scores <27 regarded as subnormal. Results— MBs were detected in 98 subjects (8%): 36 subjects (3%) classified as lobar group, 48 subjects (4%) as deep group, and 14 subjects (1%) as diffuse group. Subnormal scores were found in 76 subjects (5.9%), associated with age, education, hypertension, severe white matter hyperintensities, and distribution and number of MBs. In the final model of logistic regression analysis, the deep group (OR, 2.79; 95% CI, 1.14–6.79) was associated with subnormal scores, whereas the lobar group (OR, 0.77; 95% CI, 0.17–3.44) was not. Trend for the diffuse group did not reach the level of significance (OR, 5.01; 95% CI, 0.88–28.41). These trends were also seen in analysis using another cut-off point for subnormal score. Scores for total Mini-Mental State Examination and attention and calculation were significantly lower in the deep group and the diffuse groups compared with the without-MBs group. Conclusions— This Japanese cross-sectional study demonstrated that MB-related global cognitive dysfunction seems to occur based on hypertensive pathogenesis rather than on cerebral amyloid angiopathy.

Topography and associations of perivascular spaces in healthy adults The Kashima Scan Study

Objective: We investigated whether the topography of MRI-visible perivascular spaces (PVS) is associated with markers of specific underlying small vessel disease, including cerebral microbleed (CMB) distribution, in neurologically healthy adults. Methods: We analyzed baseline data of an ongoing Japanese population-based cohort study. PVS were rated in the basal ganglia (BG-PVS) and centrum semiovale (CSO-PVS) on axial T2-weighted MRI using a validated rating scale (score 0–4). BG-PVS degree was classified as low (score <2) or high (score ≥2). CSO-PVS degree was classified as low (score <3) or high (score ≥3). Independent demographic, clinical, and imaging factors for high degree of BG-PVS and CSO-PVS were investigated. Results: A total of 1,575 neurologically healthy adults were included (mean age 57.1 years, SD 9.7; 47% male). In multivariable analyses, high degree of BG-PVS (n = 212, 14%) was associated with deep or infratentorial CMBs (odds ratio [OR] 2.77, 95% confidence interval [CI] 1.62–4.74), a marker of hypertensive arteriopathy; by contrast, high degree of CSO-PVS (n = 357, 23%) was associated with strictly lobar CMBs (OR 2.49, 95% CI 1.35–4.61), which share risk factors with cerebral amyloid angiopathy. Both high degree of BG-PVS and CSO-PVS were associated with hypertension (OR 2.03, 95% CI 1.46–2.82 and OR 1.39, 95% CI 1.07–1.81, respectively), lacunes (OR 3.35, 95% CI 1.92–5.86; OR 1.83 95% CI 1.08–3.08), and severe white matter hyperintensities (OR 2.17, 95% CI 1.42–3.31; OR 1.35, 95% CI 0.93–1.96), but these associations were stronger for high degree of BG-PVS. Conclusions: In a neurologically healthy cohort, the associations of PVS differ according to their topography. PVS distribution may be useful for the early detection and classification of small vessel disease.

Marked cerebral atrophy is correlated with kidney dysfunction in nondisabled adults.

The relationship between kidney dysfunction, such as chronic kidney disease (CKD), and brain morphology has attracted increasing attention, but the association between kidney dysfunction and cerebral atrophy has yet to be determined. The purpose of this study was to clarify the relationship between kidney function and a substantial degree of cerebral atrophy. A total of 610 consecutive Japanese adults without neurological disorders who had undergone health screening tests of the brain were studied prospectively. Magnetic resonance imaging was performed using a 1.5-T scanner. Using a computer-assisted processing system, the percentage of cerebrum atrophy (%Cerebrum atrophy) was calculated as an index of cerebral atrophy. Atrophy was defined as >2 s.d.s below the mean %Cerebrum atrophy. The glomerular filtration rate (GFR) was estimated using the revised equations for estimated GFR from serum creatinine in Japan. Kidney function variables included the GFR value and the prevalence of subjects with GFR <60 ml min−1 per 1.73 m2. Cerebral atrophy was found in 25 (4.1%) cases. Univariate analysis showed that age, male sex, hypertension, each kidney function variable, white matter hyperintensities and lacunae were associated with cerebral atrophy. On logistic regression analysis, GFR (odds ratio (OR), 0.64; 95% confidence interval (CI), 0.42–0.98) and GFR <60 ml min−1 per 1.73 m2 (OR, 5.93; 95% CI, 1.82–19.27) were significantly associated with cerebral atrophy. On sub-analysis, GFR <60 ml min−1 per 1.73 m2 was significantly associated with cortical atrophy (OR, 3.23; 95% CI, 1.15–9.11). Decreased GFR was significantly associated with cerebral atrophy, indicating that treatment of CKD may control age-related degenerative processes of the brain.

Arterial spin-labeling MR imaging in moyamoya disease compared with clinical assessments and other MR imaging finings

PURPOSE Our purpose was to identify the causal factors for the perfusion distribution obtained with ASL-MRI by comparing ASL-MRI with clinical information and other MRI findings in moyamoya disease. METHODS Seventy-one patients with moyamoya disease underwent ASL-MRI and other MRI, including fluid-attenuated inversion recovery imaging (FLAIR) and three-dimensional time-of-flight magnetic resonance angiography (MRA) on 3.0-Tesla MRI system. Cerebral blood flow (CBF) values (ASL values) for the cerebral hemispheres (142 sides) were measured on CBF maps generated by ASL-MRI. Relationships between the ASL values and the following 9 factors were assessed: sex, family history, revascularization surgery, age at MR exam, age at onset, the steno-occlusive severity on MRA (MRA score), degree of basal collaterals, degree of leptomeningeal high signal intensity seen on FLAIR, and size of ischemic or hemorrhagic cerebrovascular accident lesion (CVA score). RESULTS Patients with a family history had significantly higher ASL values than those without such a history. There were significant negative correlations between ASL values and age at MR exam, MRA score, and CVA score. CONCLUSIONS ASL-MRI may have cause-and-effect or mutual associations with family history, current patient age, size of CVA lesion, and intracranial arterial steno-occlusive severity in Moyamoya disease.

Noninvasive method for mapping CVR in moyamoya disease using ASL-MRI

PURPOSE To project a noninvasive method for mapping cerebrovascular reserve (CVR) in moyamoya disease (MMD) using ASL-MRI. METHODS 16 MMD patients underwent cerebral blood flow (CBF) examinations by standard ASL-MRI, pulse-wave-synchronized ASL-MRI (pulsy ASL-MRI) which tagged the arterial blood coincident with a peak of a pulse wave, and single photon emission computed tomography (SPECT) imagings with iodine-123-N-isopropyl-p-iodoamphetamine in the resting (rest-IMP) and after acetazolamide challenge (ACZ-IMP). Hemispheric 32-sided cerebral blood flow (CBF) values were measured with normalized CBF maps created from standard ASL-MRI (standard-ASL value), pulsy ASL-MRI (pulsy-ASL value), rest-IMP (rest-IMP value), and ACZ-IMP (ACZ-IMP value). CVR based on rest-IMP and ACZ-IMP values (IMP-CVR) was calculated. ASL-CVR was also calculated on the basis of corrected standard-ASL values and pulsy-ASL values, which were adjusted to the ACZ-IMP values and rest-IMP values, respectively, by the least-squares method. We assessed the relationships between rest-IMP values and pulsy-ASL values, ACZ-IMP values and standard-ASL values, and IMP-CVR and ASL-CVR. RESULTS Significant relationships were observed between rest-IMP values and pulsy-ASL values (correlation coefficient (r=0.557, p<0.01)), ACZ-IMP values and standard-ASL values (r=0.825, p<0.01), and IMP-CVR and ASL-CVR (r=0.736, p<0.01). CONCLUSIONS ASL-MRI is equivalent to SPECT and that it might serve as a noninvasive method for mapping CVR in MMD.

Hemodynamic studies of intracranial dural arteriovenous fistulas using arterial spin-labeling MR imaging.

Arterial spin-labeling (ASL) magnetic resonance imaging (MRI) enables non-invasive acquisition of the brain perfusion information in cerebrovascular disease. We investigated hemodynamic changes in intracranial dural arteriovenous fistulas (DAVFs) using ASL-MRI. ASL-MRI by a Q2TIPS sequence on a 3.0-Tesla MRI was performed for three patients with Cognards IIa+b type of DAVFs before and after treatment. Perfusion images obtained by ASL-MRI (ASL images) before treatment were visually compared with those by single-photon emission computed tomography images (SPECT images). Increasing rates of temporal changes of regional perfusion values in ASL images (ASL values) before and after treatment were also calculated. In all three patients, ASL images before treatment demonstrated high perfusion in regions around the shunting areas, where normal or low perfusion were detected on SPECT images; thus, ASL images might have demonstrated the abundant arterial shunting flow via the fistulas. On days eight to 20 after treatment, ASL values around the shunt areas remained the same or decreased, and those in the regions other than the shunt areas increased in all three patients. This might have been due to a combination of the following: a decrease in shunt flow volume, an amelioration of venous congestion, and a sustained an upward shift in the autoregulation of the brain perfusion pressure. All regional ASL values decreased on days 112 and 120 after treatment in two patients, which possibly reflects a reduction in the upward shift in autoregulation. ASL-MRI might be useful for identifying the hemodynamic behavior of DAVFs before and after treatment.

Arterial Spin-labeling in Central Nervous System Infection

Purpose: To investigate the characteristics of arterial spin-labeling magnetic resonance imaging (ASL-MRI) in central nervous system (CNS) infection. Methods: Thirty-two patients with CNS infections underwent a pulsed ASL-MRI. The findings on ASL-MRI were retrospectively assessed for the pathogens as well as each of the following four pathology classified based on conventional MRI findings: non-purulent parenchymal involvement, meningeal involvement, abscess formation, and ventricular involvement. Results: Among the 17 patients with non-purulent parenchymal involvement, ASL-MRI revealed high perfusion in 8 patients (47%) and low perfusion 1 patient (6%). Especially, four of five patients (80%) with definite or suspected herpes simplex virus (HSV) infection showed high perfusion on ASL-MRI. Seventeen of 22 patients (77%) with meningeal involvement showed high perfusion along the cerebral sulci irrespective of the pathogens. Meanwhile, 4 of 16 lesions (25%) with abscess formation showed low perfusion and one of six patients (17%) with ventricular involvement had high perfusion. Conclusions: The characteristics of ASL-MRI in CNS infections were clearly delineated. ASL-MRI could be helpful for monitoring the brain function in CNS infections noninvasively.

Arterial spin-labeling MR imaging of cerebral hemorrhages.

IntroductionThe purpose of this study is to identify the characteristics of brain perfusion measured by arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cerebral hemorrhages.MethodsBrain blood flow values (CBF-ASL values) for cerebral and cerebellar hemispheres and segmented cerebral regions were measured by ASL-MRI in 19 putaminal hemorrhage patients and 20 thalamic hemorrhage patients in acute or subacute stages. We assessed the lateralities of CBF-ASL values and the relationships between CBF-ASL values and other imaging findings and clinical manifestations.ResultsBoth the 19 putaminal hemorrhage patients and the 20 thalamic hemorrhage patients had significantly low CBF-ASL values of the contralateral cerebellum in subacute stage, suggesting that ASL-MRI might delineate crossed cerebellar diaschisis (CCD). Ipsilateral low CBF-ASL values were observed in frontal lobes and thalami with a putaminal hemorrhage and lentiform nuclei, temporal lobes, and parietal lobes with a thalamic hemorrhage, suggesting that ASL-MRI showed the ipsilateral cerebral diaschisis (ICD). In the putaminal hemorrhage patients, the hematoma volume negatively affected both the bilateral cerebellar and cerebral hemispheric CBF-ASL values. In the thalamic hemorrhage patients, a concomitant intraventricular hemorrhage caused low cerebral hemispheric CBF-ASL values.ConclusionThe use of ASL-MRI is sensitive to the perfusion abnormalities and could thus be helpful to estimate functional abnormalities in cerebral hemorrhage patients.

Total Small Vessel Disease Score in Neurologically Healthy Japanese Adults in the Kashima Scan Study

Objective We explored the association between the total small vessel disease (SVD) score obtained with magnetic resonance imaging and risk factors and outcomes in the Japanese population. Methods The presence of SVD features, including lacunes, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on MRI, was summed to obtain a “total SVD score” (range 0-4). Ordinal and multinomial logistic regression analyses were performed to investigate the association of higher total SVD scores with vascular risk factors, the Mini-Mental State Examination (MMSE) score, and cerebral atrophy. Results We included 1,451 neurologically healthy adults (mean age, 57.1 years; 47% male). A multivariate ordinal logistic regression analysis showed that the total SVD score was associated with aging, hypertension, blood pressure (BP), diabetes mellitus, MMSE score, and deep cerebral atrophy, but the equal slopes assumption between scores did not hold. A multivariate multinomial logistic regression analysis (total SVD score 0=reference) showed that aging, hypertension, and BP were positively associated with scores of 1, 2, or ≥3. These effects, presented as odds ratios (ORs), increased as the score increased and were strongest with a score of ≥3 [aging (per 10-year increment), OR 4.00, 95% confidence interval (CI) 2.47-6.46; hypertension, OR 5.68, 95% CI 2.52-12.80; systolic BP (per standard deviation increase), OR 1.96, 95% CI 1.41-2.74, respectively]. Diabetes mellitus and deep cerebral atrophy tended to be associated with the SVD scores. The MMSE score showed no consistent associations. Conclusion The total SVD score may be a promising tool for indexing SVD, even in the Japanese population.