The aim of this study was to evaluate the clinical utility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) for the detection of cerebellar hypoperfusion in patients with spinocerebellar degeneration (SCD). Regional cerebral blood flow (CBF) were obtained from ASL and I-IMP single-photon emission computed tomography (SPECT) images by volume-of-interest analysis in patients with SCD (n = 16). Regional CBF were also measured by ASL in age-matched controls (n = 19) and by SPECT in separate controls (n = 17). The cerebellar CBF values were normalized to the CBF values for the whole gray matter (nCBF) in ASL and SPECT. The mean cerebellar nCBF measured by ASL was lower in patients with SCD (0.70 ± 0.09) than in the controls (0.91 ± 0.05) (p < 0.001), which was consistent with the comparison using SPECT (0.82 ± 0.05 vs. 0.98 ± 0.05, p < 0.001). The cerebellar nCBF measured by ASL significantly correlated with that determined by SPECT in patients (r = 0.56, p < 0.001). ASL imaging showed decreased cerebellar blood flow, which correlated with that measured by SPECT, in patients with SCD. These findings suggest the clinical utility of noninvasive MRI with ASL for detecting cerebellar hypoperfusion in addition to atrophy, which would aid the diagnosis of SCD.
Recent accumulating lines of evidence reveal that leptin is associated with synaptic plasticity and neuroprotective activity in the brain. In this preliminary study with a cross-sectional design, we examined the relationship between plasma leptin level and total or regional gray matter (GM) volume in 34 elderly subjects (mean age 64.5 years) with normal fasting glucose level and without dementia and metabolic syndrome by voxel-based morphometry of magnetic resonance imaging scans. Plasma leptin level showed no significant correlation with total GM volume but showed a significantly positive correlation with GM volumes in the right hippocampus, left parahippocampus, and right cerebellum with adjustments for age, gender, body mass index (BMI), and waist-to-hip ratio (W/H). Also, after adjustments for age, gender, BMI, W/H, and intracranial volume, plasma leptin level significantly positively correlated with GM volumes in the right hippocampus and bilateral cerebella but not with that in the left parahippocampus. The results of this pilot study would be beneficial for our understanding of the neuroprotective effects of leptin on human brain aging.
Decreased cerebral blood flow (CBF) response after acetazolamide administration may indicate increased cerebral blood volume (CBV) owing to reduced perfusion pressure from major cerebral artery steno-occlusive disease. However, decreased cerebral metabolic rate of oxygen (CMRO(2)) caused by neuronal damage or deafferentation may also decrease the CBF response to acetazolamide, which adds complexity to the assessment of autoregulatory vasodilatation. The purpose of this study was to investigate the relationship between CBF response to acetazolamide and CBV or CMRO(2) in a pure form of deafferentation, crossed cerebellar diaschisis (CCD). We used positron emission tomography to study 17 patients with unilateral supratentorial infarct and contralateral cerebellar hypoperfusion. The CBF response to acetazolamide was assessed by measuring baseline CBF and CBF 10 minutes after an intravenous injection of acetazolamide. Multivariate analysis was used to test the independent predictive value of the CBV and CMRO(2) at baseline with respect to the change of CBF during acetazolamide administration. Multivariate analysis revealed that in CCD CBV was significantly and independently associated with the percent change of CBF during acetazolamide administration (P <.0001), whereas CMRO(2) was not. In deafferentation, changes in CBV may account for variations in CBF response to acetazolamide and decreased CMRO(2) may not affect CBF response to acetazolamide expressed as the percent change.
Ammonia, which is considered to be the main agent responsible for hepatic encephalopathy, inhibits oxidative glucose metabolism in the brain. However, the effects of ammonia on cerebral glucose metabolism in different brain regions remains unclear. To clarify this issue, we added ammonia directly to fresh rat brain slices and measured its effects on glucose metabolism. Dynamic positron autoradiography with [(18)F]2-fluoro-2-deoxy-D-glucose and 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) colorimetric assay revealed that ammonia significantly increased the cerebral glucose metabolic rate and depressed mitochondrial function, as compared to the unloaded control in each of the brain regions examined (cerebral cortex, striatum, and cerebellum), reflecting increased glycolysis that compensates for the decrease in aerobic metabolism. Pre-treatment with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), a N-methyl-D-aspartate (NMDA) receptor antagonist, significantly attenuated these changes induced by ammonia in cerebellum, but not in cerebral cortex or striatum. The addition of ammonia induced an increase in cyclic guanosine monophosphate (cGMP) levels in cerebellum, but not in cerebral cortex or striatum, reflecting the activation of the NMDA receptor-nitric oxide-cGMP pathway. These results suggested that NMDA receptor activation is responsible for the impairment of glucose metabolism induced by ammonia specifically in cerebellum.
To clarify the role of oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD) in living patients, positron emission tomography (PET) with [(62)Cu]diacetyl-bis(N(4)-methylthiosemicarbazone) ([(62)Cu]ATSM) was applied to functional imaging of oxidative stress mainly due to mitochondrial dysfunction in the striata of patients with PD. Fifteen PD patients who presented with lateral dominant symptoms at onset and six healthy controls underwent [(62)Cu]ATSM PET. Dynamic PET data acquisition was performed, and standardized uptake values (SUVs) were obtained from the delayed phase of dynamic data by means of region of interest analysis. The striatum-to-cerebellum SUV ratio (S/C ratio) was calculated from the SUV in all subjects of the striatum and the cerebellar cortex. The mean S/C ratio of the bilateral striata of the patients (1.15±0.10) was significantly increased compared with that of the controls (1.08±0.02) (P<.05). In the patients, the S/C ratio of the bilateral striata showed a positive correlation with the Unified Parkinson's Disease Rating Scale (UPDRS) rating (r=0.52, P<.05), and the S/C ratio of the striatum contralateral to the initially affected body side showed a strong positive correlation with the UPDRS rating (r=0.62, P<.05). [(62)Cu]ATSM PET imaging demonstrated that striatal oxidative stress was enhanced in PD patients compared with the controls and increased with the progression of disease severity, particularly in the contralateral striatum. These findings indicated that oxidative stress associates with striatal neurodegeneration in PD.
This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson's disease (PD) using double brain imaging, 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM) PET and 123I-FP-CIT SPECT. Nine PD patients were studied with brain 62Cu-ATSM PET for oxidative stress and 123I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic 62Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, 62Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of 123I-FP-CIT (SUVR/SBR). 62Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson's Disease Rating Scale (UPDRS) scores or 123I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and 123I-FP-CIT SBR. Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. 62Cu-ATSM PET with 123I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.
Individuals with autism spectrum disorder (ASD) appear to have a unique awareness of their own body, which may be associated with difficulties of gestural interaction. In typically developing (TD) individuals, the perception of body parts is processed in various brain regions. For instance, activation of the lateral occipito-temporal cortex (LOTC) is known to depend on perspective (i.e., first- or third-person perspective) and identity (i.e., own vs. another person's body). In the present study, we examined how perspective and identity affect brain activation in individuals with ASD, and how perspective- and identity-dependent brain activation is associated with gestural imitation abilities. Eighteen young adults with ASD and 18 TD individuals participated in an fMRI study in which the participants observed their own or another person's hands from the first- and third-person perspectives. We examined whether the brain activation associated with perspective and identity was altered in individuals with ASD. Furthermore, we identified the brain regions the activity of which correlated with gestural imitation difficulties in individuals with ASD. In the TD group, the left LOTC was more strongly activated by viewing a hand from the third-person perspective compared with the first-person perspective. This perspective effect in the left LOTC was significantly attenuated in the ASD group. We also observed significant group differences in the perspective effect in the medial prefrontal cortex (mPFC). Correlation analysis revealed that the perspective effect in the inferior parietal lobule (IPL) and cerebellum was associated with the gestural imitation ability in individuals with ASD. Our study suggests that atypical visual self-body recognition in individuals with ASD is associated with an altered perspective effect in the LOTC and mPFC, which are thought to be involved in the physical and core selves, respectively. Furthermore, the gestural imitation difficulty in individuals with ASD might be associated with the altered activation in the IPL and cerebellum, but not in the LOTC. These findings shed light on common and divergent neural mechanisms underlying atypical visual self-body awareness and gestural interaction in ASD.