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Satoshi Minoshima

Publications and source records attributed to Satoshi Minoshima.

At least 19 recordsLinked to original sources
PubMed2006

In vivo imaging of functional disruption, recovery and alteration in rat olfactory circuitry after lesion.

Compensatory changes following disruption of neuronal circuitry have been indicated by previous imaging studies of stroke and other brain injury, but evidence of the pathways involved in such dynamic changes has not been shown in vivo. We imaged rats before and after lesion-induced disruption of the lateral olfactory tract to investigate the subsequent recovery and/or reorganization of functional neuronal circuitry. Serial magnetic resonance imaging was performed following intranasal administration of a paramagnetic track tracer Mn(2+). Images were analyzed using statistical mapping techniques in the stereotactic coordinate system. At 1 week post-lesion, Mn(2+) transport caudal to lesion was reduced as expected, and more importantly, increased transport through the anterior commissure was seen. At 4 weeks post-lesion, there was recovery of transport caudal to lesion, and increased transport through the anterior commissure extended to the contralateral olfactory cortex. Correlation analysis of regional Mn(2+) transport indicated that contralateral enhancement was not simply due to septal window spillover. This study demonstrates for the first time in vivo evidence of compensatory changes in functional neuronal activity to a contralateral pathway through the commissure following brain injury.

Administration, Intranasal↗
PubMed2006

Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease.

The type-2 vesicular monoamine transporter (VMAT2) might serve as an objective biomarker of Parkinson disease (PD) severity. Thirty-one subjects with early-stage PD and 75 normal subjects underwent continuous intravenous infusion of (+)-[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography (PET) imaging to estimate the striatal VMAT2 binding site density with equilibrium tracer modeling. Parkinson disease patients were evaluated clinically in the practically defined 'off' state with the Unified Parkinson Disease Rating Scale (UPDRS), the Hoehn and Yahr Scale (HY), and the Schwab and England Activities of Daily Living Scale (SE). In normal subjects there was age-related decline in striatal DTBZ binding, approximating 0.5% per year. In PD subjects, specific DTBZ binding was reduced in the caudate nucleus (CD; -44%), anterior putamen (-68%), and posterior putamen (PP; -77%). The PP-to-CD ratio of binding was reduced significantly in PD subjects. Dihydrotetrabenazine binding was also reduced by approximately 50% in the PD substantia nigra. Striatal binding reductions correlated significantly with PD duration and SE scores, but not with HY stage or with UPDRS motor subscale (UPDRS(III)) scores. Striatal and midbrain DTBZ binding was asymmetric in PD subjects, with greatest reductions contralateral to the most clinically affected limbs. There was significant correlation between asymmetry of DTBZ binding and clinical asymmetry measured with the UPDRS(III). In HY stage 1 and 1.5 subjects (n=16), PP DTBZ binding contralateral to the clinically unaffected body side was reduced by 73%, indicating substantial preclinical nigrostriatal pathology in PD. We conclude that (+)-[(11)C]DTBZ-PET imaging displays many properties necessary of a PD biomarker.

Adult↗
PubMed2006

In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease synapses.

OBJECTIVE: We tested the premise that cholinesterase inhibitor therapy should target butyrylcholinesterase (BuChE) in Alzheimer's disease (AD), not acetylcholinesterase (AChE) alone, because both enzymes hydrolyze acetylcholine, and BuChE is increased in AD cerebral cortex. METHODS: To examine this issue in vivo, we quantified human cerebral cortical BuChE activity using tracer kinetic estimates (k(3)) of 1-[(11)C]methyl-4-piperidinyl n-butyrate ([(11)C]BMP) hydrolysis determined by positron emission tomography. Validation of the putative positron emission tomography method included regional distribution, positive correlation with age, and attenuation by the nonselective cholinesterase inhibitor physostigmine, but no attenuation by the AChE-selective inhibitor donepezil. Positron emission tomography scans in AD patients (n = 15) and control subjects (n = 12) measured both BuChE (using [(11)C]BMP) and AChE activity (using N-[(11)C] methylpiperidin-4-yl propionate, an established method). RESULTS: As expected, AChE activity in AD cerebral cortex was decreased to 75 +/- 13% of normal (p = 0.00001). Contrary to prediction, accompanying BuChE activity also was decreased to 82 +/- 14% of normal (p = 0.001). INTERPRETATION: Failure to observe increased [(11)C]BMP hydrolysis in vivo makes it less likely that incremental BuChE contributes importantly to acetylcholine hydrolysis in AD. The findings do not support the premise that inhibitor therapy should target BuChE so as to prevent increased levels of BuChE from hydrolyzing acetylcholine in AD cerebral cortex.

Acetylcholinesterase↗
PubMed2006

Diagnosis of dementia using perfusion SPECT imaging at the patient's initial visit to a cognitive disorder clinic.

PURPOSE: This study was performed to evaluate the diagnostic accuracy of brain perfusion SPECT in patients visiting the cognitive disorder clinic for initial evaluation using 3D-SSP compared with using standard transaxial section. MATERIALS AND METHODS: Standard transaxial section displays and 3D-SSP z-score maps obtained after administration of Tc-99m ECD or I-123 IMP were randomly interpreted in 315 patients who visited initially to the cognitive disorder clinic (age 46-88 years; 162 women, 153 men). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated and receiver operating characteristic (ROC) analysis was performed. RESULTS: One hundred thirty-seven patients were clinically diagnosed with Alzheimer disease and 178 patients were diagnosed with other disorders and age-associated cognitive decline. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy calculated using standard transaxial display were 61%, 70%, 61%, 70%, and 66%, respectively, and using the 3D-SSP z-score map were 90%, 74%, 73%, 90%, and 81%, respectively. Particularly, the sensitivity value improved in mild cases compared with severe cases using 3D-SSP. Diagnostic performance with 3D-SSP was superior in both mild dementia (Az = 0.64 [section] vs 0.81 [3D-SSP], P = 0.001) and severe dementia (Az = 0.75 [section] vs 0.90 [3D-SSP], P = 0.002). CONCLUSIONS: Brain perfusion SPECT was useful for diagnosis in patients who come to the cognitive disorder clinic for initial evaluation using 3D-SSP.

Aged↗
PubMed2006

Imaging cerebral activity in recovery from chronic traumatic brain injury: a preliminary report.

People in chronic phase of traumatic brain injury (TBI) are often told that there will be no further recovery in brain function, that they are in a "static phase." Holistic Approach to NeuroDevelopment and Learning Efficiency (HANDLE), an alternative therapy, aims to improve function by teaching a series of physical and mental activities that clients perform and encouraging changes in lifestyle. Five subjects (3 males) with chronic TBI (at least 3 years since ictus) completed the HANDLE Institute's program and were prospectively evaluated. Each had six regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) scans over 7 months (scans n= 30). Paired scans were performed with injection of Tc-99m ECD to image rCBF at rest and during the HANDLE "Crossed Arm Bounce" (CAB) exercise before the program, at 3-4 months into the program, and at 6-7 months, after the program had ended. SPECT images were analyzed statistically using Neurostat in which image sets were coregistered and warped into Talaraich atlas for pairwise subtraction between conditions. Group analysis of SPECT showed that CAB activated (increased rCBF) vermis and cerebellar hemispheres in first two paired scans and anterior cingulate and vermis on the final pair. Increased rCBF at rest occurred in cerebellar hemispheres, vermis, and right dorsomedial frontal cortex. These preliminary observations suggest that there may be a role of the hindbrain (vermis and cerebellum) with HANDLE treatment of chronic TBI.

Adult↗
PubMed2005

Diagnostic value of FDG PET and salivary gland scintigraphy for parotid tumors.

PURPOSE: The purpose of this study was to examine the diagnostic value of the combination of F-18 fluorodeoxyglucose (FDG) PET and Tc-99m pertechnetate salivary gland scintigraphy in parotid tumors. MATERIALS AND METHODS: Seventy-two patients with benign parotid gland tumors (n = 52), malignant parotid tumors (n = 12), and inflammation (n = 8) underwent both FDG PET and salivary gland scintigraphy within 1 week, and 66 of the patients also underwent gallium scintigraphy. All patients were negative on their first fine-needle aspiration (FNA). RESULTS: Malignant parotid tumors showed significantly higher FDG uptake (standard uptake values [SUVs]) than both benign tumors and inflammation, except in Warthin's tumor (5.82 +/- 3.95 vs. 2.07 +/- 1.33; P <0.01). Although the SUV values of Warthin's tumor and malignant parotid tumors overlapped somewhat, Warthin's tumor did demonstrate increased radiotracer uptake, and it was reliably distinguished from other parotid gland tumors by the use of salivary gland scintigraphy. Considering a SUV value >3 as being positive for malignancy and excluding Warthin's tumor on the basis of salivary gland scintigraphy, sensitivity and specificity of FDG PET were 75% and 80%, respectively. These results were superior to those of gallium scintigraphy (58% and 72%, respectively). CONCLUSIONS: Although the diagnostic value of FDG PET in the differentiation of malignant from benign parotid gland tumors was limited because of the high FDG uptake in some benign tumors, and particularly pleomorphic adenomas, combining salivary gland scintigraphy with FDG PET may help to negate this drawback, and this combination may be a more promising approach for differentiation of various parotid gland tumors in patients compared with nondiagnostic needle aspiration.

Adolescent↗
PubMed2005

Comparison of conventional region of interest and statistical mapping method in brain single-photon emission computed tomography for prediction of hyperperfusion after carotid endarterectomy.

OBJECTIVE: Hyperperfusion after carotid endarterectomy (CEA) has been proposed as the main mechanism of intracerebral hemorrhage, which is a disastrous complication. The aim of this study was to compare the predictive value of cerebral blood flow (CBF) abnormalities for hyperperfusion after CEA with the conventional region of interest (ROI) analysis and statistical brain mapping analysis. METHODS: For 46 patients with unilateral carotid stenosis of 70% or more, CBF and cerebral vasoreactivity were investigated with resting and acetazolamide-challenge single-photon emission computed tomography before CEA and 1 day after CEA. Three-dimensional stereotactic surface projection (3-D-SSP) analysis of CBF changes was performed by automatic quantification with a predefined template. RESULTS: Logistic regression analysis demonstrated CBF reduction (z-score) to be the only significant variable for postoperative hyperperfusion on 3-D-SSP with thalamic normalization but no significant variable with the ROI method. Receiver operating characteristic (ROC) analysis demonstrated significant improvement in the predictive value of CBF reduction (z-score) on 3-D-SSP (area under the ROC curve = 0.93) in comparison with the ROI method (area under the ROC curve = 0.78) (P = 0.049). According to the optimal cutoff values provided by ROC analysis, patients were categorized into two groups: Type I (CBF decrease < 20%, n = 23) and Type II (CBF decrease > or = 20%, n = 23) on ROI analysis and Type A (z-score < or = 2, n = 40) and Type B (z-score > 2, n = 6) on 3-D-SSP. There was a significant difference in incidence of hyperperfusion between Type A (1 of 40) and Type B (5 of 6) on 3-D-SSP (P = 0.00003) but not between Type I (1 of 23) and Type II (5 of 23) on ROI analysis. Cerebral vasoreactivity did not show significant value in the prediction of hyperperfusion with either the ROI or the 3-D-SSP method. CONCLUSION: Objective assessment of CBF status, especially baseline CBF reduction (z-score), with automatic quantification by 3-D-SSP with normalization had a higher diagnostic value than conventional ROI analysis to identify patients at risk for hyperperfusion after CEA.

Acetazolamide↗
PubMed2005

False-positive "necklace sign" on whole-body thyroid cancer survey--a case report.

A woman with papillary thyroid carcinoma treated with surgery and postoperative 131I returned 4 y later for a whole-body survey. The imaging results initially suggested disease recurrence but were later found to be false positive and due to 131I uptake in a necklace that had been contaminated by the patient's saliva. This case stresses the importance of having the patient remove all jewelry before undergoing a radioiodine survey.

Adult↗
PubMed2005

Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.

UNLABELLED: Patients with mild cognitive impairment (MCI) represent a risk population for progressing to dementia of the Alzheimer type (DAT). However, clinical criteria do not ensure reliable individual prognosis in these patients. The objective of this longitudinal, prospective study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility, as defined by an APOEepsilon4-positive genotype, with regard to the early diagnosis of DAT in patients with MCI. METHODS: In 30 patients with the diagnosis of MCI (16 female, 14 male; age, 70 +/- 8 y), baseline and follow-up examinations (mean observation period, 16 mo) were performed. In all patients, the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET. Individual PET data were screened for findings suggestive of Alzheimer's disease (AD), with the help of an automated computer program. After stereotactical normalization of the PET images, this program performs an observer-independent statistical comparison with an age-matched reference database (n = 22). RESULTS: In 43% of all MCI subjects, a PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline (PET+); 57% of all MCI patients were carriers of the APOE epsilon4 allele (e4+). In 40% of all patients, progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation. Statistical evaluation revealed the best results for PET with regard to early diagnosis of DAT in MCI patients (sensitivity, 92%; specificity, 89%). Classification according to the APOE genotype was significantly less successful (sensitivity, 75%; specificity, 56%). However, a combination of both diagnostic tests allowed early diagnosis with either very high specificity (PET+ AND e4+: sensitivity, 67%; specificity, 100%) or very high sensitivity (PET+ OR e4+: sensitivity, 100%; specificity, 44%). CONCLUSION: (18)F-FDG PET of cerebral glucose metabolism is a valuable diagnostic tool for the prediction of clinical outcome in individual MCI patients. Results are superior to the exclusive assessment of the APOE genotype. A combination of both functional imaging and genotyping may allow an early high-risk or low-risk stratification of patients with either very high sensitivity or very high specificity. This may be valuable, for example, for patient selection in scientific studies.

Aged↗
PubMed2005

Rapid scanning protocol for brain (18)F-FDG PET: a validation study.

UNLABELLED: Although (18)F-FDG PET is an established technique to assess brain glucose use, a shorter imaging time is preferable for patient convenience and increased throughput. The aim of this study was to validate a brain (18)F-FDG PET protocol more rapid than the conventional protocol. METHODS: For comparison of normalized metabolic activities, brain (18)F-FDG PET was performed on 60 healthy subjects and 25 patients with probable Alzheimer's disease (AD), and an additional 20 healthy subjects served as a control group to assess diagnostic performance between the conventional and rapid scanning protocols. Conventional scans were acquired for a total of 20 min (a 10-min emission and a 10-min transmission). Immediately after conventional scanning, rapid scanning was performed for a total of 4 min (a 3-min emission and a 1-min transmission). PET images were anatomically standardized using NEUROSTAT, with pixel values normalized to the individual global value. Two database sets, from the 2 protocols, were compared by regional values and pixel-by-pixel analysis. A receiver-operating-characteristic analysis was performed for comparison of diagnostic accuracy between the 2 protocols. A kinetic simulation study was also performed to examine the possible difference due to the time lag between the protocols. RESULTS: Although small differences in normalized activity were found in several regions in the healthy subjects between the 2 protocols, no significant difference was found in any region in the patient group. The coefficients of variation of the normalized activity were 20%-30% larger in the rapidly scanned images, but the mean z images and their coefficient-of-variation images did not differ. The kinetic simulation study suggested that the differences were caused by the time lag between the 2 protocols. No significant differences were found in area under the receiver-operating-characteristic curves, and the diagnostic accuracies for the detection of AD were virtually equal between the 2 protocols. CONCLUSION: The rapid scanning protocol used in the present study could provide results nearly equivalent to data from the conventional protocol. Thus, it is feasible to use this rapid protocol to detect AD, without losing diagnostic accuracy.

Aged↗
PubMed2004

Diagnosis of suspected Alzheimer's disease is improved by automated analysis of regional cerebral blood flow.

PURPOSE: Accurate diagnosis of Alzheimer's disease (AD), the most common form of dementia, remains difficult. In order to assess whether fully automated stereotactic surface projection (3D-SSP) presentation contributes to the diagnosis of AD by single-photon emission computed tomography (SPECT), we investigated the diagnostic accuracy of transaxial display with and without 3D-SSP analysis as well as the correlation between cerebral perfusion in different cortical areas and the mini mental score (MMS). METHODS: Seventy-two patients referred because of cognitive impairment were included in the study. According to the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's disease and Related Disorders Association (ADRDA) criteria, 27 patients were diagnosed as having probable AD while 45 were classified as non-AD patients. 3D-SSP was used to quantify the regional cerebral blood flow (rCBF) acquired from SPECT imaging. RESULTS: Compared with the transaxial section presentation alone, 3D-SSP presentation improved the area under the receiver operating curve (p<0.05) as well as intra-observer (k=0.73 vs 0.88) and inter-observer (k=0.50 vs 0.84) reproducibility. Upon normalisation of regional to thalamic activity, multiple regression analysis revealed a strong correlation between the MMS and rCBF in the right parietal cortex (p=0.002). CONCLUSION: Addition of 3D-SSP to the transaxial section display of ECD-SPECT studies improves the reproducibility and the diagnostic performance in respect of AD in patients with cognitive impairment and provides a valid tool for assessment of the severity of cortical perfusion abnormalities in such patients.

Adult↗
PubMed2004

A comparison of classification methods for differentiating fronto-temporal dementia from Alzheimer's disease using FDG-PET imaging.

Flurodeoxyglucose positron emission tomography (FDG-PET) is being explored to determine its ability to differentiate between a diagnosis of Alzheimer's disease (AD) and fronto-temporal dementia (FTD). We have examined statistical discrimination procedures to help achieve this purpose and compared the results to visual ratings of FDG-PET images. The methods are applied to a data set of 48 subjects with autopsy confirmed diagnoses of AD or FTD (these subjects come from a multi-centre collaborative study funded by the National Alzheimer's Coordinating Center). FDG-PET images are composed of thousands of voxels (volume elements) so one is left with a situation where there are vastly more variables than subjects. Therefore, it is necessary to perform a data reduction before a statistical procedure can be applied. Approaches using both the entire image and summary statistics calculated on a number of volumes of interest (VOI) are examined. We performed the data reduction techniques of principal components analysis (PCA) and partial least-squares (PLS) on the entire image and then used linear discriminant analysis (LDA), quadratic (QDA) or logistic regression (LR) to classify subjects as having AD or FTD. Some of these methods achieve diagnostic accuracy (as assessed by leave-one-out cross-validation) that is similar to visual ratings by expert raters. Methods using PLS appear to be more successful. Averaging or using VOI data may also be helpful.

Alzheimer Disease↗
PubMed2004

Statistical mapping of functional olfactory connections of the rat brain in vivo.

The olfactory pathway is a unique route into the brain. To better characterize this system in vivo, rat olfactory functional connections were mapped using magnetic resonance (MR) imaging and manganese ion (Mn2+) as a transport-mediated tracer combined with newly developed statistical brain image analysis. Six rats underwent imaging on a 1.5-T MR scanner at pre-administration, and 6, 12, 24, 36, 48, and 72 h and 5.5, 7.5, 10.5, and 13.5 days post-administration of manganese chloride (MnCl2) into the right nasal cavity. Images were coregistered, pixel-intensity normalized, and stereotactically transformed to the Paxinos and Watson rat brain atlas, then averaged across subjects using automated image analysis software (NEUROSTAT). Images at each time point were compared to pre-administration using a one-sample t statistic on a pixel-by-pixel basis in 3-D and converted to Z statistic maps. Statistical mapping and group averaging improved signal to noise ratios and signal detection sensitivity. Significant transport of Mn2+ was observed in olfactory structures ipsilateral to site of Mn2+ administration including the bulb, lateral olfactory tract (lo) by 12 h and in the tubercle, piriform cortex, ventral pallidum, amygdala, and in smaller structures such as the anterior commissure after 24 h post-administration. MR imaging with group-wise statistical analysis clearly demonstrated bilateral transsynaptic Mn2+ transport to secondary and tertiary neurons of the olfactory system. The method permits in vivo investigations of functional neuronal connections within the brain.

Amygdala↗
PubMed2004

Neurochemical imaging of dementias.

Neurochemical imaging is one of the most established "molecular" imaging techniques. There have been tremendous efforts expended to develop radioligands specific to each neurochemical system. Investigational applications of neurochemical imaging in dementing disorders are extensive. Cholinergic, dopaminergic, and serotonergic systems, as well as benzodiazepine receptors, opioid receptors, and glutamatergic receptors have been imaged in Alzheimer disease and other dementing disorders. These investigations have provided important insights into disease processes in living human patients. The clinical diagnostic use of neurochemical imaging for dementing disorders is currently limited, but this technique is used to help develop therapeutic drugs at multiple levels.

Acetylcholine↗
PubMed2004

Subacute necrotizing encephalopathy in a pig-tailed macaque (Macaca nemestrina) that resembles mitochondrial encephalopathy in humans.

A male pig-tailed macaque (Macaca nemestrina), approximately 5 years old, was found to be vision-impaired and to have profound behavioral abnormalities, including hyperactivity and self-injurious behavior that was not amenable to amelioration by environmental enrichment. Facial and skeletal dysmorphisms also were noted. Magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning revealed areas of possible infarction in the occipital lobes and megaventriculosis. At necropsy, following euthanasia for humane reasons, severe polio- and leukoencephalomalacia accompanied by megaventriculosis were seen in both occipital lobes and in several sulci of the parietal and frontal lobes. Light microscopic findings included loss of neocortical structure, with necrosis, neuronal loss, astrogliosis, vascular proliferation, mild spongiosis, and demyelination. The extent and severity of lesions were most pronounced in the occipital lobes and were greater in the left than in the right hemisphere. Other lesions included mild bilateral atrophy of the optic nerves, thymic involution, necrotizing dermatitis due to trauma, and a spectrum of spermatozoal abnormalities. The imaging and gross and light microscopic changes found in this animal resemble the mitochondrial encephalopathies of humans; this was corroborated by results of immunohistochemical analysis demonstrating decreased expression of enzymes of the mitochondrial oxidative complex ([OC]-I, -III, and -IV) in brain and muscle, and detection of fibrinogen immunoreactivity in neurons and glial cells. The spermatozoal defects may represent yet another aspect of a mitochondrial defect.

Animals↗