Comparative examination of the pons and corpus callosum as reference regions for quantitative evaluation in positron emission tomography imaging for Alzheimer's disease using 11C-Pittsburgh Compound-B.

OBJECTIVES: Standardised uptake value ratio (SUVR) is usually obtained by dividing the SUV of the region of interest (ROI) by that of the cerebellar cortex. Cerebellar cortex is not a valid reference in cases where amyloid ß deposition or lesions are present. Only few studies have evaluated the use of other regions as references. We compared the validity of the pons and corpus callosum as reference regions for the quantitative evaluation of brain positron emission tomography (PET) using 11C-PiB compared to the cerebellar cortex. METHODS: We retrospectively evaluated data from 86 subjects with or without Alzheimer's disease (AD). All subjects underwent magnetic resonance imaging, PET imaging, and cognitive function testing. For the quantitative analysis, three-dimensional ROIs were automatically placed, and SUV and SUVR were obtained. We compared these values between AD and healthy control (HC) groups. RESULTS: SUVR data obtained using the pons and corpus callosum as reference regions strongly correlated with that using the cerebellar cortex. The sensitivity and specificity were high when either the pons or corpus callosum was used as the reference region. However, the SUV values of the corpus callosum were different between AD and HC (p < 0.01). CONCLUSIONS: Our data suggest that the pons and corpus callosum might be valid reference regions.

Involvement of the Precuneus/Posterior Cingulate Cortex Is Significant for the Development of Alzheimer's Disease: A PET (THK5351, PiB) and Resting fMRI Study.

Background: Imaging studies in Alzheimer's disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

[Case of cerebral venous thrombosis with a high plasma lipoprotein (a) level].

A 28-year-old man was admitted to our hospital because of severe headache and diplopia. Enhanced CT of the head revealed defects of contrast enhancement in the superior sagittal sinus and the right transverse sinus. Accordingly, he was diagnosed as suffering from cerebral venous thrombosis. The patient made a good recovery after receiving anticoagulant therapy. Investigations revealed a high plasma lipoprotein (a) [Lp (a)] level of 142 mg/ dl. We thought that his high Lp (a) level was associated with a thrombotic tendency. His mother also had an elevated plasma Lp (a) level of 45 mg/dl. Cerebral venous thrombosis of unknown etiology is not rare. In such patients, we should investigate the plasma Lp (a) level.

Neuronal and glial tau pathology in early frontotemporal lobar degeneration-tau, Pick's disease subtype.

Frontotemporal lobar degeneration-tau, Pick's disease subtype (PiD) is one of the major types of frontotemporal dementia, but its pathogenesis and disease mechanisms remain unclear. Here, we report a case of very early PiD. The patient was a 63-year-old healthy woman without dementia or any apparent psychosis. She was admitted to the hospital with multiple organ failure, and died three days later. The brain weighed 1050g and showed focal atrophy of the parahippocampal gyrus and right medial temporal lobe. Microscopically, neuronal loss and gliosis were limited to the atrophic areas. Surprisingly, Pick bodies (PiBs) and ballooned neurons were abundant throughout the bilateral temporal cortices, including the dentate gyrus. Cortical lamination of PiBs was predominant in the upper layer (layer II>VI), and the size of early PiBs tended to be smaller than that in severely affected areas. Numerous glial tau-positive inclusions (astrocytic inclusions, oligodendroglial coiled bodies, and threads) were found not only in the cerebral cortex but also in the temporal white matter. The neuropathological findings in this case suggest that PiB formation started long before the appearance of clinical symptoms and that PiB formation originating from small neurons may differ from other tau aggregations such as neurofibrillary tangles.

Inclusion-positive cell types in adult-onset intranuclear inclusion body disease: implications for clinical diagnosis.

The distribution of inclusions in adult-onset type intranuclear inclusion body disease (INIBD) has not been fully described. We analyzed the clinical and pathological changes of three autopsy cases of adult type INIBD and provide a detailed description of the distribution of inclusions in nervous system and visceral organs. Although patients showed cognitive decline and autonomic dysfunction, there were no specific symptoms related to general organs. The neuropathological changes responsible for cognitive decline and autonomic dysfunction were considered to be white matter changes in the cerebral hemispheres and inclusions in the autonomic nervous system, e.g., in the sympathetic ganglia and myenteric plexus. Alterations of spongiosis with both myelin and axon loss in the cerebral white matter seemed to be related to dysfunction of astrocytes with intranuclear inclusions. In visceral organs, the inclusions were much more widely distributed than previously appreciated and included renal mesangial cells, adrenal sustentacular cells, fibrocytes, Kupffer cells, pancreatic centroacinar and ductal epithelial cells. Since skeletal muscle cells, Schwann cells and smooth muscle cells were also inclusion positive, we propose that biopsy of muscle, peripheral nerve or rectum may prove useful for the clinical diagnosis of INIBD.