Secondary thalamic atrophy related to brain infarction may contribute to post-stroke cognitive impairment.

BACKGROUND AND PURPOSE: The thalamus is a key brain hub that is globally connected to many cortical regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or cognitive correlates. This study investigates associations between thalamic volumes and post-stroke cognitive function. METHODS: Participants with non-thalamic brain infarcts (3-42 months) underwent MRI and cognitive testing. Focal infarcts and thalami were traced manually. In cases with bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics were extracted using a standardized and previously validated neuroimaging pipeline. Age and gender-matched healthy controls provided normal comparative thalamic volumes. Thalamic atrophy was considered when the volume exceeded 2 standard deviations greater than the controls. RESULTS: Thalamic volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.5 cc, p < 0.001) and right (4.4 ± 1.4 vs. 5.5 ± 0.6 cc, p < 0.001) thalamic volumes in the controls. After controlling for head-size and global brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume (ß= -0.069, p=0.024). Left thalamic atrophy correlated significantly with poorer cognitive performance (ß = 4.177, p = 0.008), after controlling for demographics and infarct volumes. CONCLUSIONS: Our results suggest that the remote effect of infarction on ipsilateral thalamic volume is associated with global post-stroke cognitive impairment.

Discriminative Utility of Transcranial Magnetic Stimulation-Derived Markers of Cortical Excitability for Transient Ischemic Attack.

BACKGROUND: Several guidelines currently recommend acute diffusion weighted imaging (DWI) for the detection of ischemia in transient ischemic attack (TIA). However, DWI hyperintensities resolve early and only 30%-50% with clinically defined TIA show acute DWI positivity. A recent meta-analysis reported an unexplained 7-fold variation in DWI positivity in TIA across studies, concluding that DWI does not provide a consistent basis for defining ischemia. Intracortical excitability, measured using transcranial magnetic stimulation (TMS), has previously been shown to be altered after TIA and associated with ABCD2 scores; however, whether altered cortical excitability is associated with clinical and DWI-based definitions of TIA remains unclear. METHODS: Individuals with TIA symptoms (N = 23; mean age = 61 ± 12) were prospectively recruited and underwent DWI and paired-pulse TMS. Multivariate linear regression was used to estimate associations between TMS-derived excitability thresholds, and clinical TIA diagnosis, and imaging-based evidence of cerebral ischemia (DWI positivity). Area under the curve (AUC) analyses was used to compare the discriminability of TMS-derived thresholds and clinical TIA diagnoses. RESULTS: Thresholds for intracortical inhibition in the TIA-unaffected hemisphere were significantly associated with the clinical diagnosis of TIA. No associations between TMS-derived thresholds and DWI positivity were observed. TMS thresholds showed low-moderate discriminability and values differed by age (65+) and sex. CONCLUSIONS: In this small sample, TMS-derived markers of intracortical excitability were associated with clinical TIA diagnoses but not DWI positivity. Our results provide preliminary evidence for the potential discriminative utility of TMS for the diagnosis of TIA and highlight the need for future work in larger cohorts.

Measurement of the length of vertebrobasilar arteries: A three-dimensional approach.

Under the assumption that neurovascular compression can be caused by elongation or kinking of the artery, we measured the length of each section of the vertebrobasilar artery, compared the lengths between various age groups, and evaluated the involvement of the arterial sections in brain stem compression in 1000 cases. The lengths of the posterior inferior cerebellar artery (PICA)-union of both vertebral arteries (union), union-anterior inferior cerebellar artery (AICA), AICA-superior cerebellar artery (SCA), and union- superior cerebellar artery were measured using an arterial length measuring tool applied to three-dimensional images. The presence of arterial compression of the brain stem was also evaluated. The mean age of the participants was 66.8 ± 12.9 years, and 44.8% were men. Intraclass correlation coefficients for both inter-rater reliability and intra-rater reliability were high in all sections. The vessel lengths of left AICA-SCA (P < 0.001), left union-SCA (P < 0.0001), left PICA-union (P = 0.03), right AICA-SCA (P = 0.002), right union-SCA (P < 0.0001), and right PICA-union (P = 0.04) increased with age, but each R2 was less than 0.05. Brain stem compression by PICA or vertebral artery was identified in 13.8% of cases. The proportion of the presence of brain stem compression was significantly higher in the cases with arterial elongation than in those without (P = 0.01). Vessel length increased with age, but age had a relatively small impact on the elongation of vertebrobasilar arteries. Brain stem compression might be caused by kinking of the artery rather than arterial elongation.

Central auditory processing in adults with chronic stroke without hearing loss: A magnetoencephalography study.

OBJECTIVE: Stroke lesions in non-auditory areas may affect higher-order central auditory processing. We sought to characterize auditory functions in chronic stroke survivors with unilateral arm/hand impairment using auditory evoked responses (AERs) with lesion and perception metrics. METHODS: The AERs in 29 stroke survivors and 14 controls were recorded with single tones, active and passive frequency-oddballs, and a dual-oddball with pitch-contour and time-interval deviants. Performance in speech-in-noise, mistuning detection, and moving-sound detection was assessed. Relationships between AERs, behaviour, and lesion overlap with functional networks, were examined. RESULTS: Despite their normal hearing, eight patients showed unilateral AER in the hemisphere ipsilateral to the affected hand with reduced amplitude compared to those with bilateral AERs. Both groups showed increasing attenuation of later components. Hemispheric asymmetry of AER sources was reduced in bilateral-AER patients. The N1 wave (100 ms latency) and P2 (200 ms) were delayed in individuals with lesions in the basal-ganglia and white-matter, while lesions in the attention network reduced the frequency-MMN (mismatch negativity) responses and increased the pitch-contour P3a response. Patients' impaired speech-in-noise perception was explained by AER measures and frequency-deviant detection performance with multiple regression. CONCLUSION: AERs reflect disruption of auditory functions due to damage outside of temporal lobe, and further explain complexity of neural mechanisms underlying higher-order auditory perception. SIGNIFICANCE: Stroke survivors without obvious hearing problems may benefit from rehabilitation for central auditory processing.

PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells.

The Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is a novel breast cancer cell expressing peptide, originally found in the neural cells as an anti-apoptotic factor, could inhibit cell apoptosis and enhance cell migration and invasion in human breast cancer cell lines. The expression of PCP4/PEP19 is induced by estrogens in estrogen receptor-positive (ER+) MCF-7 cells but also highly expressed in ER- SK-BR-3 cells. In this study, we investigated the effects of PCP4/PEP19 on aromatase gene expression in MCF-7 and SK-BR-3 human breast cancer cells. In SK-BR-3 cells but not in MCF-7 cells, PCP4/PEP19 knockdown by siRNA silencing decreased the aromatase expression in gene transcriptional level. When PCP4/PEP19 was overexpressed by CMV promoter-driven PCP4/PEP19 expressing plasmid transfection, aromatase gene transcription increased in SK-BR-3 cells. This aromatase gene transcription is mainly mediated through promoter region PI.1, which is usually active in the placental tissue but not in the breast cancer tissue. These results indicate a new function of PCP4/PEP19 that would enhance aromatase gene upregulation to supply estrogens in heterogeneous cancer microenvironment.

Variability in stroke motor outcome is explained by structural and functional integrity of the motor system.

Biomarkers that represent the structural and functional integrity of the motor system enable us to better assess motor outcome post-stroke. The degree of overlap between the stroke lesion and corticospinal tract (CST Injury) is a measure of the structural integrity of the motor system, whereas the left-to-right motor cortex resting state connectivity (LM1-RM1 rs-connectivity) is a measure of its functional integrity. CST Injury and LM1-RM1 rs-connectivity each individually correlate with motor outcome post-stroke, but less is understood about the relationship between these biomarkers. Thus, this study investigates the relationship between CST Injury and LM1-RM1 rs-connectivity, individually and together, with motor outcome. Twenty-seven participants with upper limb motor deficits post-stroke completed motor assessments and underwent MRI at one time point. CST Injury and LM1-RM1 rs-connectivity were derived from T1-weighted and resting state functional MRI scans, respectively. We performed hierarchical multiple regression analyses to determine the contribution of each biomarker in explaining motor outcome. The interaction between CST Injury and LM1-RM1 rs-connectivity does not significantly contribute to the variability in motor outcome. However, inclusion of both CST Injury and LM1-RM1 rs-connectivity explains more variability in motor outcome, than either alone. We suggest both biomarkers provide distinct information about an individual's motor outcome.

The effects of music-supported therapy on motor, cognitive, and psychosocial functions in chronic stroke.

Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music-supported therapy (MST) in chronic stroke on motor, cognitive, and psychosocial functions compared to conventional physical training (GRASP). Twenty-eight adults with unilateral arm and hand impairment were randomly assigned to MST (n = 14) and GRASP (n = 14) and received 30 h of training over a 10-week period. The assessment was conducted at four time points: before intervention, after 5 weeks, after 10 weeks, and 3 months after training completion. As for two of our three primary outcome measures concerning motor function, all patients slightly improved in Chedoke-McMaster Stroke Assessment hand score, while the time to complete Action Research Arm Test became shorter in the MST group. The third primary outcome measure for well-being, Stroke Impact Scale, was improved for emotion and social communication earlier in MST and coincided with the improved executive function for task switching and music rhythm perception. The results confirmed previous findings and expanded the potential usage of MST for enhancing quality of life in community-dwelling chronic-stage survivors.

Blood Pressure Variability in Acute Ischemic Stroke: Influence of Infarct Location in the Insular Cortex.

BACKGROUND: The aim of this study was to elucidate the influence of insular infarction on blood pressure (BP) variability and outcomes according to the region of the insular cortex affected. METHODS: A total of 90 patients diagnosed with acute unilateral ischemic stroke were registered. The BP variability was calculated over 24 h after admission (hyperacute) and for 2-3 days after admission (acute). Patients were classified into groups of right and left, and then right anterior, right posterior, left anterior, and left posterior insular infarction. RESULTS: Patients with insular infarction showed a significantly larger infarct volume, higher modified Rankin scale scores, and lower SD and coefficient of variation (CV) of -systolic BP in the hyperacute phase than shown by patients without insular infarction (p < 0.01, p < 0.01, p = 0.02, and p = 0.03, respectively). The SD and CV of systolic BP in the hyperacute phase showed significant differences among the 3 groups with right insular infarction, with left insular infarction, and without insular infarction (p < 0.05 and p < 0.05, respectively). There was a tendency for the systolic BP variability to be lower in patients with right anterior insular infarction than in patients with infarcts in other areas. CONCLUSION: The right insular cortex, especially the anterior part, might be a hub for autonomic nervous regulation.

Neural coupling between contralesional motor and frontoparietal networks correlates with motor ability in individuals with chronic stroke.

Movement is traditionally viewed as a process that involves motor brain regions. However, movement also implicates non-motor regions such as prefrontal and parietal cortex, regions whose integrity may thus be important for motor recovery after stroke. Importantly, focal brain damage can affect neural functioning within and between distinct brain networks implicated in the damage. The aim of this study is to investigate how resting state connectivity (rs-connectivity) within and between motor and frontoparietal networks are affected post-stroke in correlation with motor outcome. Twenty-seven participants with chronic stroke with unilateral upper limb deficits underwent motor assessments and magnetic resonance imaging. Participants completed the Chedoke-McMaster Stroke Assessment as a measure of arm (CMSA-Arm) and hand (CMSA-Hand) impairment and the Action Research Arm Test (ARAT) as a measure of motor function. We used a seed-based rs-connectivity approach defining the motor (seed=contralesional primary motor cortex (M1)) and frontoparietal (seed=contralesional dorsolateral prefrontal cortex (DLPFC)) networks. We analyzed the rs-connectivity within each network (intra-network connectivity) and between both networks (inter-network connectivity), and performed correlations between: a) intra-network connectivity and motor assessment scores; b) inter-network connectivity and motor assessment scores. We found: a) Participants with high rs-connectivity within the motor network (between M1 and supplementary motor area) have higher CMSA-Hand stage (z=3.62, p=0.003) and higher ARAT score (z=3.41, p=0.02). Rs-connectivity within the motor network was not significantly correlated with CMSA-Arm stage (z=1.83, p>0.05); b) Participants with high rs-connectivity within the frontoparietal network (between DLPFC and mid-ventrolateral prefrontal cortex) have higher CMSA-Hand stage (z=3.64, p=0.01). Rs-connectivity within the frontoparietal network was not significantly correlated with CMSA-Arm stage (z=0.93, p=0.03) or ARAT score (z=2.53, p=0.05); and c) Participants with high rs-connectivity between motor and frontoparietal networks have higher CMSA-Hand stage (rs=0.54, p=0.01) and higher ARAT score (rs=0.54, p=0.009). Rs-connectivity between the motor and frontoparietal networks was not significantly correlated with CMSA-Arm stage (rs=0.34, p=0.13). Taken together, the connectivity within and between the motor and frontoparietal networks correlate with motor outcome post-stroke. The integrity of these regions may be important for an individual's motor outcome. Motor-frontoparietal connectivity may be a potential biomarker of motor recovery post-stroke.

Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase.

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. METHODS: One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute-subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. RESULTS: Multiple linear regression analyses were completed. Although larger infarcts (ß=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (ß=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (ß=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. CONCLUSIONS: In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Progression of limb apraxia in corticobasal syndrome: neuropychological and functional neuroimaging report of a case series.

The current study described the progression of limb apraxia in seven corticobasal syndrome patients through a comprehensive battery, including both gesture production tasks and conceptual tool/action knowledge tasks. The examination of the behavioral and neuroimaging (SPECT) data revealed two patient subgroups. One group consisted of patients with preserved conceptual tool/action knowledge, relatively mild gesture production and neuropsychological deficits with few significantly hypoperfused regions of interest. The other group consisted of those whose conceptual tool/action knowledge and general cognition eventually deteriorated and who were quite severely affected in their gesture production performance. These patients were characterized by bilateral hypoperfusion in parietal regions and in one case bilateral anterior cingulate regions.

Differentiating between visual hallucination-free dementia with Lewy bodies and corticobasal syndrome on the basis of neuropsychology and perfusion single-photon emission computed tomography.

INTRODUCTION: Dementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities. METHODS: Prospectively recruited case-control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them. RESULTS: The Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P <0.001 and F (1, 42) =14.0, P =0.001 respectively) and the delayed visual reproduction of the Wechsler Memory Scale-Revised (F (1, 36) =9.7, P =0.004). The Lewy body group also demonstrated reduced perfusion in the left occipital pole compared to the corticobasal group (F (1,57) =7.4, P =0.009). At autopsy, the Lewy body cases all demonstrated mixed dementia with Lewy bodies, Alzheimer's disease and small vessel arteriosclerosis, while the corticobasal cases demonstrated classical corticobasal degeneration in five, dementia with agyrophilic grains + corticobasal degeneration + cerebral amyloid angiopathy in one, Progressive Supranuclear Palsy in two, and Frontotemporal Lobar Degeneration-Ubiquitin/TAR DNA-binding protein 43 proteinopathy in one. MRI measures were not significantly different between the patient groups. CONCLUSIONS: Reduced perfusion in the left occipital region and worse episodic memory performance may help to distinguish between DLB cases who have never manifested with visual hallucinations and CBS at earlier stages of the disease. Development of reliable neuropsychological and imaging markers that improve diagnostic accuracy will become increasingly important as disease modifying therapies become available.

Congenital absence of the mammillary bodies: a novel finding in a well-studied case of developmental amnesia.

Individuals with developmental amnesia experience compromised development of episodic memory for details of personal life events, believed to relate to changes to the hippocampus after birth. Here we report the very rare discovery of aplasia of the mammillary bodies, hypogenesis of the fornix, and abnormal hippocampal shape and orientation in H.C., a well-documented case of selectively compromised episodic memory development who is the subject of numerous published empirical articles. These anatomical abnormalities are highly suggestive of disrupted extended hippocampal system development very early in gestation, despite an original diagnosis of developmental amnesia and assumed perinatal hypoxia. These findings provide a unique window into the normal function of the mammillary bodies, fornices, and related anterior nuclei of the thalamus bilaterally. The results also encourage re-examination of the pathological basis of developmental amnesia in other cases reported in the literature.

Alzheimer's disease, cerebrovascular disease, and the ß-amyloid cascade.

Alzheimer's disease (AD), considered the commonest neurodegenerative cause of dementia, is associated with hallmark pathologies including extracellular amyloid-ß protein (Aß) deposition in extracellular senile plaques and vessels, and intraneuronal tau deposition as neurofibrillary tangles. Although AD is usually categorized as neurodegeneration distinct from cerebrovascular disease (CVD), studies have shown strong links between AD and CVD. There is evidence that vascular risk factors and CVD may accelerate Aß 40-42 production/ aggregation/deposition and contribute to the pathology and symptomatology of AD. Aß deposited along vessels also causes cerebral amyloid angiopathy. Amyloid imaging allows in vivo detection of AD pathology, opening the way for prevention and early treatment, if disease-modifying therapies in the pipeline show safety and efficacy. In this review, we review the role of vascular factors and Aß, underlining that vascular risk factor management may be important for AD prevention and treatment.

Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the Sunnybrook Dementia Study.

PURPOSE: Quantification methods for white matter hyperintensities (WMH) on Magnetic Resonance Imaging are heterogeneous, deterring their application. This study compared three WMH rating scales, varying in complexity, and a volumetric method, to evaluate trade-offs between complexity and clinical utility in differentiating dementia subgroups and in correlating with cognition. METHODS: WMH were rated using the Fazekas, Age-Related White Matter Changes (ARWMC) and Scheltens scales, and segmented by computational volumetry in 108 patients with Alzheimer's Disease (AD), 23 with Mild Cognitive Impairment (MCI) and 34 normal controls (NC). Global and hippocampal atrophy, age and education, were accounted for in correlations of WMH with cognitive domains. RESULTS: Intra- and inter-rater reliability were high (intraclass correlation coefficients = 0.88-0.97) across rating scales. WMH scores of all scales were highly correlated with volumes (Spearman r = 0.78-0.90, Ps < 0.001), as well as with each other (Spearman r = 0.86-0.91, Ps < 0.001). The Fazekas scale showed significant separation between AD, MCI and NC using non-parametric analysis, while the ARWMC and Scheltens' scales, and WMH volumes demonstrated significant correlations (standardized ß = -0.19 to -0.24, Ps < 0.05) with cognitive domain scores using multivariate regression analysis, controlling for age, education, global and hippocampal atrophy in patients with AD. CONCLUSIONS: This study suggests that the degree of complexity of WMH rating scales did not affect validation against WMH volumes, but did vary in validation against cognition. The simplest scale performed best in separating cognitive subgroups, but the more complex scales and quantification correlated better with cognitive measures, especially executive function. Hence the best choice of scale depends on the particular application.

Alzheimer's disease and infection: do infectious agents contribute to progression of Alzheimer's disease?

Infection with several important pathogens could constitute risk factors for cognitive impairment, dementia, and Alzheimer's disease (AD) in particular. This review summarizes the data related to infectious agents that appear to have a relationship with AD. Infections with herpes simplex virus type 1, picornavirus, Borna disease virus, Chlamydia pneumoniae, Helicobacter pylori, and spirochete were reported to contribute to the pathophysiology of AD or to cognitive changes. Based on these reports, it may be hypothesized that central nervous system or systemic infections may contribute to the pathogenesis or pathophysiology of AD, and chronic infection with several pathogens should be considered a risk factor for sporadic AD. If this hypothesis holds true, early intervention against infection may delay or even prevent the future development of AD.

Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis.

BACKGROUND: As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs). METHODS: We compared 2 sets of partial volume corrected serotonin 1a receptor binding potentials (BPs) resulting from manual vs. semi-automated methods. BPs were obtained from subjects meeting consensus criteria for frontotemporal degeneration and from age- and gender-matched healthy controls. Two trained raters provided each set of data to conduct comparisons of inter-rater mean image processing time, rank order of BPs for 9 PET scans, intra- and inter-rater intraclass correlation coefficients (ICC), repeatability coefficients (RC), percentages of the average parameter value (RM%), and effect sizes of either method. RESULTS: SABRE saved approximately 3 hours of processing time per PET subject over manual delineation (p < .001). Quality of the SABRE BP results was preserved relative to the rank order of subjects by manual methods. Intra- and inter-rater ICC were high (>0.8) for both methods. RC and RM% were lower for the manual method across all ROIs, indicating less intra-rater variance across PET subjects' BPs. CONCLUSION: SABRE demonstrated significant time savings and no significant difference in reproducibility over manual methods, justifying the use of SABRE in serotonin 1a receptor radioligand PET imaging analysis. This implies that semi-automated ROI delineation is a valid methodology for future PET imaging analysis.

Quantitative assessment of cerebral blood flow in genetically confirmed spinocerebellar ataxia type 6.

BACKGROUND: Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by CAG trinucleotide expansion. The characteristics of regional cerebral blood flow (rCBF) in SCA6 patients have not been established, whereas it has been reported that decreased rCBF in the cerebrum seems to be a remote effect of cerebellar impairment in other cerebellar disorders. OBJECTIVE: To clarify the characteristics of rCBF, including cerebro-cerebellar relationship, and its correlation with clinical manifestations in patients with genetically confirmed SCA6 using quantitative assessment of rCBF by brain single-photon emission computed tomography (SPECT). DESIGN: Technetium Tc 99m ethyl cysteinate dimer SPECT study using a Patlak plot. Patients Hiroshima University Hospital, Hiroshima, Japan. Ten patients with SCA6 and 9 healthy controls. Main Outcome Measure The rCBF of the cerebellar vermis, cerebellar hemisphere, and frontal lobes. RESULTS: In SCA6 patients, rCBF was decreased only in the cerebellar vermis and hemisphere compared with healthy controls, and this was inversely correlated with duration of illness. The rCBF in the frontal lobes was slightly correlated with duration of illness without statistical significance. The rCBF in the vermis was inversely correlated with severity of dysarthria, but there was no significant correlation with CAG repeated expansions. CONCLUSIONS: Decrease in rCBF was found only in the cerebellum and was associated with duration of illness, dysarthria and ataxia, and cerebellar atrophy. No remote effect of cerebellar hypoperfusion was found in the SCA6 patients.

Magnetization transfer measurements of brain structures in patients with multiple system atrophy.

To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.