Three-dimensional Stereotactic Surface Projection Research Articles

Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

Cerebellar blood perfusion is a diagnostic, but not a prognostic, marker for parkinsonian-dominant type multiple system atrophy

IntroductionMultiple system atrophy (MSA) is clinically characterized by various neurological symptoms. According to the diagnostic criteria, MSA is classified into parkinsonian-dominant type (MSA-P) or cerebellar ataxia-dominant type (MSA-C) based on the predominant signs displayed. Recently, N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT), a radiological examination evaluating brain perfusion, has been successful in detecting cerebellar hypoperfusion in MSA-P patients, demonstrating its utility in the early detection of cerebellar dysfunction. In this study, we further explored whether this cerebellar hypoperfusion impacts the clinical features of MSA-P, whether it is observable in patients without cerebellar symptoms, and, most importantly, whether it influences the prognosis of MSA-P. MethodsWe conducted a retrospective analysis of 88 MSA patients who were admitted to our department for the last fifteen years. Clinical data were collected, and cerebellar perfusion was examined using 123I-IMP SPECT. This analysis includes the application of the three-dimensional stereotactic surface projection (3D-SSP) technique and Z-score. ResultsCerebellar perfusion decreased in MSA-P patients without cerebellar ataxia, compared to healthy individuals (p = 0.0017). The Receiver Operating Characteristic (ROC) curve demonstrated a moderate ability to distinguish MSA-P patients without cerebellar ataxia (MSA-Pp) from healthy controls (AUC = 0.6832). Among MSA-Pp, those exhibiting cerebellar hypoperfusion showed relatively improved neurological prognosis, although the difference was not statistically significant when compared to those with normal cerebellar perfusion. ConclusionAssessing cerebellar perfusion through IMP-SPECT proves valuable in detecting subclinical cerebellar dysfunction in MSA-Pp. Importantly, cerebellar hypoperfusion does not correlate with a poorer neurological prognosis.

Progression of regional cortical cholinergic denervation in Parkinson's disease.

Cortical cholinergic deficits contribute to cognitive decline and other deficits in Parkinson's disease. Cross-sectional imaging studies suggest a stereotyped pattern of posterior-to-anterior cortical cholinergic denervation accompanying disease progression in Parkinson's disease. We used serial acetylcholinesterase PET ligand imaging to characterize the trajectory of regional cholinergic synapse deficits in Parkinson's disease, testing the hypothesis of posterior-to-anterior progression of cortical cholinergic deficits. The 16 Parkinson's disease subjects (4 females/12 males; mean age: 64.4 ± 6.7 years; disease duration: 5.5 ± 4.2 years; Hoehn & Yahr stage: 2.3 ± 0.6 at entry) completed serial 11C-methyl-4-piperidinyl propionate acetylcholinesterase PET scans over a 4-8 year period (median 5 years). Three-dimensional stereotactic cortical surface projections and volume-of-interest analyses were performed. Cholinergic synapse integrity was assessed by the magnitude, k 3, of acetylcholinesterase hydrolysis of 11C-methyl-4-piperidinyl propionate. Based on normative data, we generated Z-score maps for both the k 3 and the k 1 parameters, the latter as a proxy for regional cerebral blood flow. Compared with control subjects, baseline scans showed predominantly posterior cortical k 3 deficits in Parkinson's disease subjects. Interval change analyses showed evidence of posterior-to-anterior progression of cholinergic cortical deficits in the posterior cortices. In frontal cortices, an opposite gradient of anterior-to-posterior progression of cholinergic deficits was found. The topography of k 3 changes exhibited regionally specific disconnection from k 1 changes. Interval-change analysis based on k 3/k 1 ratio images (k 3 adjustment for regional cerebral blood flow changes) showed interval reductions (up to 20%) in ventral frontal, anterior cingulate and Brodmann area 6 cortices. In contrast, interval k 3 reductions in the posterior cortices, especially Brodmann areas 17-19, were largely proportional to k 1 changes. Our results partially support the hypothesis of progressive posterior-to-cortical cholinergic denervation in Parkinson's disease. This pattern appears characteristic of posterior cortices. In frontal cortices, an opposite pattern of anterior-to-posterior progression of cholinergic deficits was found. The progressive decline of posterior cortical acetylcholinesterase activity was largely proportional to declining regional cerebral blood flow, suggesting that posterior cortical cholinergic synapse deficits are part of a generalized loss of synapses. The disproportionate decline in regional frontal cortical acetylcholinesterase activity relative to regional cerebral blood flow suggests preferential loss or dysregulation of cholinergic synapses in these regions. Our observations suggest that cortical cholinergic synapse vulnerability in Parkinson's disease is mediated by both diffuse processes affecting cortical synapses and processes specific to subpopulations of cortical cholinergic afferents.

Distribution and progression of cerebral amyloid angiopathy in early-onset V30M (p.V50M) hereditary ATTR amyloidosis

Background Cerebral amyloid angiopathy (CAA) is becoming the most common and serious complications in long-lived hereditary ATTR amyloidosis patients. It is therefore imperative to elucidate the characteristics of ATTR-type CAA and develop useful biomarkers. Methods We enrolled 34 ATTRv amyloidosis patients with the V30M (p.V50M) variant for analysis with three-dimensional stereotactic surface projection z score imaging of Pittsburgh compound B (PiB)-PET. Results Eight patients exhibited central nervous system (CNS) symptoms. Seven patients suffered transient focal neurologic episodes, and 2 patients each experienced cerebellar haemorrhages or cognitive decline. The amount of 11C-PiB accumulation increased as a function of disease duration. 11C-PiB-PET abnormalities were seen at 8 years from onset and were associated with CNS manifestations from 12 years. The annual increase rate of the standardised uptake value ratio (SUVR) in female patients was significantly higher than in male patients. CNS amyloid deposition started in the upper middle surface of the cerebellar cortex, and then spread out over the entire surface of the cerebellum, Sylvian fissure, and anterior part of the longitudinal fissure of the cerebrum. Conclusions PiB-PET is a useful biomarker for the early detection and treatment evaluation of ATTR-type CAA. Female gender is associated with more rapid progression of ATTR-type CAA.

Unclassified fluent variants of primary progressive aphasia: distinction from semantic and logopenic variants.

Primary progressive aphasia, a neurodegenerative syndrome, presents mainly with language impairment. Both semantic and logopenic variants are fluent variants of primary progressive aphasia. Before the research criteria of primary progressive aphasia were proposed, progressive fluent aphasias, such as progressive anomic aphasia, transcortical sensory aphasia and Wernicke’s aphasia, were reported as classical progressive fluent aphasias seen in Alzheimer’s disease. However, since the research criteria of primary progressive aphasia were established, classical fluent variants (other than semantic and logopenic variants) have been neglected and have not been included in the current classification of primary progressive aphasia. This study aimed to determine whether unclassified fluent variants (other than semantic and logopenic variants) can be manifestations of primary progressive aphasia. This study also reconfirmed the characteristics of classical progressive fluent aphasia, such as progressive anomic aphasia, progressive transcortical sensory aphasia and progressive Wernicke’s aphasia as unclassified fluent variants of primary progressive aphasia, using comparison with the current model of primary progressive aphasia. Twelve consecutive patients with an unclassified fluent variant other than semantic or logopenic variant underwent language, neurological, neuropsychological and neuroimaging (MRI and single-photon emission computed tomography) testing. Based on comprehensive language tests, we redefined the diagnoses as primary progressive anomic aphasia (n = 8), primary progressive transcortical sensory aphasia (n = 3) and primary progressive Wernicke’s aphasia (n = 1). Anomic aphasia was characterized by anomia but preserved repetition and comprehension; transcortical sensory aphasia by relatively preserved repetition but poor word comprehension; and Wernicke’s aphasia by poor repetition and word comprehension. In patients with anomic aphasia, voxel-based morphometry of MRI data revealed cortical atrophy, which was most prominent in the temporoparietal lobes, with no obvious lateralization; in two-thirds of patients with transcortical sensory aphasia and in one patient with Wernicke’s aphasia, it revealed atrophy, predominantly in the left temporoparietal lobe. Statistical analysis of single-photon emission computed tomography using three-dimensional stereotactic surface projections revealed patterns of left-sided hypoperfusion in the majority of patients. The temporal and parietal lobes were involved in all cases; the degree of hypoperfusion was higher in patients with transcortical sensory aphasia or Wernicke’s aphasia than in patients with anomic aphasia. The present study demonstrated the clinical and imaging features of 12 patients with an unclassified fluent variant of primary progressive aphasia, which we redefined as primary progressive anomic aphasia, primary progressive transcortical sensory aphasia and primary progressive Wernicke’s aphasia. Classical fluent variants other than semantic and logopenic variants can be found in primary progressive aphasia.

Relationship between cerebral blood flow reduction patterns on scintigraphy and nonmotor symptoms in new-onset Lewy body disease.

This study aimed to investigate the relationship between patterns of reduced cerebral blood flow (CBF) evaluated by means of 123I-N-isopropyl-p-iodoamphetamine ([123I]IMP) scintigraphy and nonmotor symptoms in new-onset Lewy body disease (Parkinson's disease and dementia with Lewy bodies [DLB]). Twenty-four patients diagnosed with new-onset Parkinson's disease or DLB underwent [123I]IMP CBF scintigraphy at St. Marianna Medical University Hospital between January 1, 2010, and March 30, 2018. The reductions in CBF in various brain regions were analyzed using the three-dimensional stereotactic surface projection method and were compared to standard database values, yielding extent values (%). The extent values were evaluated in relation to the presence/absence of motor or nonmotor symptoms such as visual hallucinations, auditory hallucinations, delirium, depression, delusions, and dementia. The extent value was 100% in the angular, supramarginal, and lingual gyri; 95% in the orbital gyri; and 92.6% in the fusiform gyri. The extent value in patients without hallucinations and those with visual hallucinations was 41.2% and 54.3%, respectively, in the frontal lobe (p = 0.02) and 33.3% and 51.0%, respectively, in the medial prefrontal gyri (p = 0.02). Age-adjusted multivariate analysis showed that extent values in the frontal lobe were associated with visual hallucinations (odds ratio: 1.09, 95% confidence interval 1.00-1.18, p = 0.04). The above results show that the CBF is reduced in several areas of the cerebral cortex and suggest an association between reduced blood flow in the frontal lobe and the appearance of visual hallucinations in patients with new-onset DLB.

Localizing Epileptic Foci Before Surgery in Patients With MRI-Negative Refractory Epilepsy Using Statistical Parameter Mapping and Three-Dimensional Stereotactic Surface Projection Based on 18F-FDG PET.

Patients with refractory epilepsy are not only free of seizures after resecting epileptic foci, but also experience significantly improved quality of life. Fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) is a promising avenue for detecting epileptic foci in patients with magnetic resonance imaging (MRI)-negative refractory epilepsy. However, the detection of epileptic foci by visual assessment based on 18F-FDG PET is often complicated by a variety of factors in clinical practice. Easy imaging methods based on 18F-FDG PET images, such as statistical parameter mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), can objectively detect epileptic foci. In this study, the regions of surgical resection of patients with over 1 year follow-up and no seizures were defined as standard epileptic foci. We retrospectively analyzed the sensitivity of visual assessment, SPM and 3D-SSP based on 18F-FDG PET to detect epileptic foci in MRI-negative refractory epilepsy patients and obtained the sensitivities of visual assessment, SPM and 3D-SSP are 57, 70 and 60% respectively. Visual assessment combined with SPM or 3D-SSP can improve the sensitivity of detecting epileptic foci. The sensitivity was highest when the three methods were combined, but decreased consistency, in localizing epileptic foci. We conclude that SPM and 3D-SSP can be used as objective methods to detect epileptic foci before surgery in patients with MRI-negative refractory epilepsy. Visual assessment is the preferred method for PET image analysis in MRI-negative refractory epilepsy. When the visual assessment is inconsistent with the patient’s electroclinical information, SPM or 3D-SSP was further selected to assess the epileptic foci. If the combination of the two methods still fails to accurately locate the epileptic foci, comprehensive evaluation can be performed by combining the three methods.

Effect of different parietal hypoperfusion on neuropsychological characteristics in mild cognitive impairment.

In early-stage amnestic mild cognitive impairment (aMCI), differences in the neuropsychological characteristics of each individual are subtle. We investigated differences in neuropsychological performance between aMCI patients with and without hypoperfusion in the medial parietal regions (MP). We further compared patients with hypoperfusion in the left and right lateral parietal regions. We examined 165 aMCI patients (mean age: 76.8 ± 5.5 years; 87 women) who had undergone neuropsychological measurement and single-photon emission computed tomography. We classified participants into two subgroups with and without hypoperfusion: MP hypoperfusion (+) and MP hypoperfusion (-); classification was based on Z-scores (calculated by three-dimensional stereotactic surface projection technique) of three regions of interest in the parietal lobes (i.e. MP regions including posterior cingulate cortex and precuneus and left and right inferior parietal lobules (lateral parietal regions)). The MP hypoperfusion (-) group was classified into left lateral parietal hypoperfusion (+) and right lateral parietal hypoperfusion (+) subgroups. We performed either univariate or multivariate ancova to compare neuropsychological scores for continuous variables between groups and examined dichotomous variables using χ2 tests. In the overall aMCI sample, scores on logical memory delayed recall in the MP hypoperfusion (+) group were significantly lower than those in the MP hypoperfusion (-) group. Total scores on Rey-Osterrieth Complex Figure Test delayed recall were also marginally lower in the MP hypoperfusion (+) group than in the MP hypoperfusion (-) group. Comparisons of neuropsychological test scores between the left and right lateral parietal hypoperfusion (+) groups revealed no significant differences. The present findings suggest that MP hypoperfusion (+) is associated with more robust memory deficits than MP hypoperfusion (-). Combining neuropsychological tests and single-photon emission computed tomography findings may be useful for early detection of cognitive decline in aMCI.

Brain hypometabolic changes in 14 adolescent-adult patients with Niemann-Pick disease type C assessed by 18F-fluorodeoxyglucose positron emission tomography.

Niemann Pick disease type C (NPC) is a rare progressive neurovisceral lysosomal disorder caused by autosomal recessive mutations in the NPC1 or NPC2 genes. 18F-fluorodeoxyglucose (FDG) is a positron-emitting glucose analogue for non-invasive imaging of brain metabolism. FDG PET is commonly used for dementia imaging but its specific application to NPC is rarely described. This is a retrospective study of all baseline brain FDG PET performed for NPC patients. Images were assessed using a normal database statistical comparison of metabolic changes expressed in standard deviations and three-dimensional Stereotactic Surface Projection maps. Typical hypometabolic patterns in NPC were identified. We further investigated any correlation between the degree of regional brain hypometabolism and the Iturriaga clinical severity scale. Brain FDG PET images of 14 adolescent-adult NPC patients were analysed, with mean age of 35years. We found significant frontal lobe hypometabolism in 12 patients (86%), thalamic hypometabolism in eight patients (57%) and variable parietal lobe hypometabolism in 13 patients (93%). Hypometabolic changes were usually bilateral and symmetric. Ten out of 13 ataxic patients showed cerebellar or thalamic hypometabolism (sensitivity 77%, specificity 100%). Linear regression analysis showed frontal lobe hypometabolism to have the best correlation with the Iturriaga clinical scale (R2 = 0.439; p = 0.01). We found bilateral symmetric hypometabolism of the frontal lobes, thalami and parietal lobes (especially posterior cingulate gyrus) to be typical of adolescent-adult NPC. Ataxia was commonly associated with cerebellar or thalamic hypometabolism. Frontal lobe hypometabolism showed the best inverse correlation with clinical severity.

A Pioneering Paper That Provided a Tool for Accurate, Observer-Independent Analysis of 18F-FDG Brain Scans in Neurodegenerative Dementias.

Minoshima’s innovative paper included in this anniversary issue of JNM built on advances in basic research and clinical brain imaging to present an objective, automated method to assess 18F-FDG PET scans in individual patients with cognitive decline ([1][1]). With the widespread use of 18F-FDG in

Improvement in gait function after carotid endarterectomy is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex: a 123I-iomazenil SPECT study.

Carotid endarterectomy (CEA) often restores cerebral perfusion and neurotransmitter receptor function, which is seen on early and late images, respectively, on brain I-iomazenil single-photon emission computed tomography (SPECT). The reliability of gait-related parameters obtained using a triaxial accelerometer, a portable device for gait assessment, has been confirmed with test-retest measurements. The purpose of the present prospective cohort study was to determine whether improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex. Gait testing using a triaxial accelerometer was performed preoperatively and 6 months postoperatively in 64 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%). I-iomazenil SPECT was also performed with scanning within 30 min (early images) and at 180 min (late images) after tracer administration before and after surgery. SPECT data were analyzed using a three-dimensional stereotactic surface projection, and motor (Brodmann 4) and premotor (Brodmann 6) cortexes in each hemisphere were combined and defined as the motor-related cortex. Based on preoperative and postoperative gait testing, seven patients (11%) showed postoperative improved gait. Logistic regression analysis revealed that postoperative increase in I-iomazenil uptake in the motor-related cortex ipsilateral to surgery on early [95% confidence interval (CI), 4.32-365.21; P = 0.0477) or late (95% CI, 9.45-1572.57; P = 0.0173) images was an independent predictor of postoperative improved gait. Improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex.

Relationship between decreased cerebral blood flow and amnesia after microsurgery for anterior communicating artery aneurysm

ObjectivePostoperative amnesia after surgery for anterior communicating artery aneurysm might be associated with the damage of the basal forebrain. Our purpose was to verify whether decreased regional cerebral blood flow (rCBF) in basal forebrain could be related to the degree of postoperative amnesia.MethodsRegional voxel rCBF data analyzed using three-dimensional stereotactic surface projection on 123I-IMP-SPECT were compared between ten patients with postoperative amnesia and 13 normal subjects. The Severity (average Z score of the voxels with a Z score that exceeds a threshold value of 2) was calculated. The cerebral lobes with rCBF exhibiting Severity > 2 in all patients were identified. In these lobes, we then examined whether there was a gyrus exhibiting Severity that was negatively related to memory quotients (MQs).ResultsIn the right subcallosal gyrus, there was a significant negative correlation between Severity and visual MQ (ρ= − 0.884, p = 0.0007) or general MQ (ρ =− 0.853, p = 0.0017). In the right anterior cingulate gyrus, there was a significant negative correlation between Severity and verbal MQ (ρ = − 0.769, p = 0.0092). In the right rectal gyrus, there was a significant negative correlation between Severity and general MQ (ρ = − 0.811, p = 0.0044). No significant correlations were found between Severity in other brain regions and verbal, visual, or general MQ.ConclusionsThe decreased rCBF in the subcallosal gyrus included in the basal forebrain, anterior cingulate gyrus, and the rectal gyrus in the right hemisphere was related to postoperative amnesia.

Clinical utility of the normal database of 123I-iodoamphetamine brain perfusion single photon emission computed tomography for statistical analysis using computed tomography-based attenuation correction: a multicenter study

We have established a common normal database (NDB) with applicability in multicenter settings for the statistical analysis of brain perfusion single photon emission computed tomography (SPECT) with triple energy window scatter correction, computed tomography-based attenuation correction (CTAC), and spatial resolution compensation. This study aimed to compare the CTAC normal database (CTAC-NDB) with conventional normal databases for the statistical analysis of 123I-iodoamphetamine (123I-IMP) brain perfusion SPECT at three institutions and to assess the clinical efficiency of CTAC-NDB. We recruited 45 patients (26 men and 19 women; mean age, 74.2 ± 3.9years; Mini-Mental State Examination score, 19.8 ± 6.1) with Alzheimer's disease (AD, n = 26), dementia with Lewy bodies (DLB, n = 9), and mild cognitive impairment (n = 10) from three institutions. Three-dimensional stereotactic surface projection (3D-SSP) technique was used to analyze data obtained from the 123I-IMP brain perfusion SPECT images compared with both CTAC-NDB and conventional NDB. We visually assessed each 3D-SSP z score map to determine the changes in specific findings, such as AD/DLB pattern. Furthermore, the stereotactic extraction estimation analysis software was used to measure the regional z score severity and extent as a semiquantitative assessment. In the visual assessment, all cases exhibited clearer findings with CTAC-NDB than with conventional NDB in the parietotemporal association cortex as well as in the inferior temporal, frontal, and lateral occipital cortices. Contrarily, the findings from the medial cerebral regions, including the precuneus and the posterior cingulate, became indistinct in 71% of the cases and remained unchanged in 25% of the cases. In the semiquantitative analysis, a similar tendency was observed in the mean z score in the three institutions included in the study. Using the CTAC-NDB, the findings in the vicinity of the cranium became increasingly clear, whereas those in the medial surface of the brain became less defined or remained unchanged. These findings were confirmed via a semiquantitative analysis. Moreover, similar changes in the reduction pattern were observed in the three institutions. Therefore, the new database with CTAC might be applicable in other institutions. Data collected in this study may serve as a CTAC-NDB.

Selective neuronal damage and blood pressure in atherosclerotic major cerebral artery disease

ObjectiveIn patients with atherosclerotic major cerebral artery disease, low blood pressure might impair cerebral perfusion, thereby exacerbate the risk of selective neuronal damage. The purpose of this retrospective study was...

Biopathological Significance of Early-Phase Amyloid Imaging in the Spectrum of Alzheimer's Disease.

Amyloid imaging with positron emission tomography (PET) often comes with glucose metabolic imaging in diagnosis of Alzheimer's disease (AD). The present purpose was to explore the clinical valence of early amyloid-β (Aβ) PET scans to determine whether they could substitute for other imaging biomarkers (early and delayed Aβ images of 11C-Pittsburgh compound B (PIB) and 18F-fluorodeoxyglucose (FDG) images) in the AD spectrum. Thirty healthy control subjects, 20 patients with mild cognitive impairment, and 45 patients with AD underwent 11C-PIB and 18F- FDG PET. Image analyses were performed with three-dimensional stereotactic surface projection and Brodmann's area regions-of-interest methods. Since early accumulation of PIB (ePIB) reflects blood flow, we classified all subjects according to the level of ePIB in the posterior cingulate gyrus, precuneus, and lateral parietal cortex. We compared the PET parameters (ePIB, delayed-phase PIB accumulation or dPIB, FDG) to determine whether ePIB-based categorization reflected Aβ deposition in a Braak stage-related fashion. We found that ePIB images were similar to 18F-FDG images and that the progress of Aβ deposition deduced from the reduction in ePIB index was similar to the pathological progress of Braak staging. A decrease in the ePIB level in the posterior cingulate gyrus, precuneus, and parietal cortex was shown to correspond to greater and wider Aβ deposition in the medial frontal, anterior, and posterior cingulate gyri. The early-phase 11C-PIB index can be an alternative to the neurogenerative markers of glucose hypometabolism and reflects the Braak stage of Aβ deposition in the living AD brain.

Age-related increase in GABAA receptor distribution in the prefrontal cortex

Profound insight into age-related changes in γ-aminobutyric acid type A receptor (GABAA-R) distribution using iodine-123-iomazenil single photon emission computed tomography (IMZ-SPECT) can contribute to accurate in vivo evaluation. We evaluated the age-related changes in prefrontal cortex (PFC), which is the key region involved in various neurological and psychiatric diseases. In this study, IMZ-SPECT imaging data of 21 healthy males with an age range of 22–59 (mean, 38 ± 12) years were analyzed using three-dimensional stereotactic surface projection (3D-SSP). The Z-score images of the younger group (age < 40, n = 11) and the older group (age ≥ 40, n = 10) were compared. Subsequently, the mean RI-count ratios calculated for each Brodmann area (BA) by stereotactic extraction estimation method were compared between these groups. Thereafter, linear regression analysis between age and RI-count ratio was performed for all enrolled subjects. In the result, IMZ accumulation increased in bilateral BA10, 11, and the BA47 (left hemisphere) in the older group compared with the younger group. Furthermore, regression analysis demonstrated a significant positive correlation between age and RI-count ratio in these areas. Our findings indicate that GABAA-R distribution in the PFC relatively increases with age. Therefore, we concluded that the age-related changes should be considered to accurately evaluate pathophysiology of neurological and psychiatric diseases.

Influence of Pre-existing Cognitive Impairment on Rehabilitation Outcomes in Patients with Cerebral Infarction

The present study determined the effects of pre-existing cognitive impairment (PreCI) on the rehabilitation outcomes in patients with cerebral infarction. From June 2013 to August 2015, we classified 52 patients with unilateral cerebral hemispheric infarction into the PreCI and non-PreCI group based on three-dimensional stereotactic surface projection (3D-SSP) cerebral blood flow (CBF) decrease images and the past history of dementia. Furthermore we investigated the related clinical factors and functional independence measure (FIM). 1. Multivariate analysis revealed that the most important factors that affect total FIM at discharge were age, National institutes of Health Stroke Scale (NIHSS) and the Mini-Mental State Examination (MMSE) (R²=0.756). 2. The mean CBF values (P<0.05) were significantly associated with lesion volume, (P<0.001, P<0.05), the NIHSS score (P<0.001, P<0.01), the MMSE score (P<0.001, P<0.005), and total FIM (P<0.005, P<0.05) at discharge. 3. Both cognitive and motor FIM at discharge were significantly lower in the PreCI group (P<0.005, P<0.005). 4. The MMSE score of ZSAM abnormal group was significantly lower in the case of NIHSS score<10 of lesion and non lesion sides. PreCI, age, and neurological severity, affected the outcomes of stroke rehabilitation Therefore, the diagnosis of PreCI is considered important for effective stroke rehabilitation. (Received August 3, 2017; Accepted February 9, 2018; Published June 1, 2018).

RCBF and cognitive impairment changes assessed by SPECT and ADAS-cog in late-onset Alzheimer's disease after 18months of treatment with the cholinesterase inhibitors donepezil or galantamine.

Late-onset Alzheimer's disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.

Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder

ObjectivesDepression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. MethodsWe performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. ResultsEvery SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. ConclusionHypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship.

Relationships between cognitive impairment on ADAS-cog and regional cerebral blood flow using SPECT in late-onset Alzheimer's disease.

The aim of this study was to examine brain hypoperfusion and its relationship with cognitive dysfunction in late-onset Alzheimer's disease (AD). Forty patients with late-onset AD and not receiving acetylcholinesterase inhibitors were recruited from outpatient clinics. We examined cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain perfusion using single-photon emission computed tomography, and analyzed classified gyrus level segments with three-dimensional stereotactic surface projection and the stereotactic extraction estimation method level 3. ADAS-cog subscales were grouped into three domains: language, memory, and praxis. Patients with late-onset AD showed an apparent reduction in regional cerebral blood flow (rCBF) with a z score >1.5 in the frontal, temporal, and limbic lobes, with lesser reduction in the parietal and occipital lobes. Although hypoperfusion in the orbital, rectal, and subcallosal gyri of the frontal lobe was prominent, rCBF in the inferior frontal gyrus of the frontal lobe was significantly correlated with ADAS-cog total and language and praxis subscale scores. The parahippocampal gyrus of the limbic lobe was also significantly correlated with the ADAS-cog total, language, and praxis subscale scores. Additionally, the cingulate of the limbic lobe was significantly related with ADAS-cog memory. In spite of lesser hypoperfusion, the posterior cingulate gyrus of the limbic lobe was significantly related with ADAS-cog total, language, and memory subscale scores. Further, each subdivision of ADAS-cog was found to be related with various brain regions.