New Computer-Aided Diagnosis of Dementia Using Positron Emission Tomography: Brain Regional Sensitivity-Mapping Method

Purpose: We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score) derived from the Brodmann area (BA) sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) from normal adults (NL). Methods: We studied 101 adults (NL: 40, AD: 37, MCI: 24) who underwent 18FDG positron emission tomography (PET) measurement. We divided NL and AD groups into two categories: a training group with (Category A) and a test group without (Category B) clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a summated index (Total Z score) by utilizing the sensitivitydistribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients. Results: In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate ADconverters from non-converters in MCI group. Conclusions: The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study.浜松医科大学学位論文　医博第695号（平成27年3月16日

Neural correlates of standing imagery and execution in Parkinsonian patients: The relevance to striatal dopamine dysfunction.

It has been reported that the cerebellar vermis is equally involved in both motor imagery about axial movement and the actual execution of postural balance in healthy human subjects, but this finding is yet to be explored in Parkinson's disease (PD). We therefore investigated the neuronal responses during observation of standing posture, imagination of standing and the assumption of an upright posture in ten drug-naïve PD patients using positron emission tomography (PET) with [15O]H2O and evaluated dopamine dysfunction by measuring the level of dopamine transporter binding of [11C]CFT. Within-group statistical parametric mapping (SPM) analysis showed similar cerebellar activation during imagination of standing and its real execution between the PD and control groups (12 healthy subjects); i.e., increases in regional cerebral blood flow (rCBF) were observed in the anterior cerebellar vermis during motor imagination and the posterior vermis during standing. A comparison between the groups showed that the motor execution of standing significantly activated the superior part of the posterior vermis (declive VI) and the paracentral sulcus region in the PD patients, while the prefrontal cortices were deactivated during standing (p<0.001 uncorrected). Correlation analysis within the PD group revealed that the postural rCBF increases in the cerebellar vermis (pyramis) were negatively correlated with putaminal [11C]CFT binding (p<0.01, r = 0.94) and that the postural rCBF reductions in the orbitofrontal cortex were positively correlated with caudate [11C]CFT binding (p<0.05, r = 0.70). These results suggest that while the neural circuits for postural imagery and execution are intact in PD, standing performance, which requires more recruitment of dopaminergic control, may result in compensatory overstimulation of the cerebellar vermis and paracentral foot area in PD patients. Hyperactivity in these areas along with mesocortical hypofunction may be pathophysiological aspects of postural control in PD patients. Hence, our findings would help understand the modifications observed within the neural networks in relationship with postural performance, and possible compensatory mechanisms in PD

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer\u27s disease.

Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer\u27s disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [C]PBB3 and [C]DPA713

Medial Orbitofrontal Cortex Is Associated with Fatigue Sensation

Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performed H2O  15 positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue

Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor.

BACKGROUND: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies. METHODOLOGY: Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups. CONCLUSION: The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients