Diagnostic approach with Z-score mapping to reduce artifacts caused by cerebral atrophy in regional CBF assessment of mild cognitive impairment (MCI) and Alzheimer's disease by [99mTc]-ECD and SPECT.

PURPOSE: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy. MATERIALS AND METHODS: [99mTc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically. RESULTS: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%. CONCLUSION: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies.

Detecting Comparative Features of Comprehensive Geriatric Assessment through the International Classification of Functioning, Disability, and Health Linkage: A Web-Based Survey.

Multidimensional assessments are important in evaluating the overall health of older adults. The comprehensive geriatric assessment (CGA) is a representative framework; however, the burden associated with the CGA has led to the development of simplified multidimensional tools. Comparing these tools to the CGA can help utilize them effectively. However, a direct comparison is challenging owing to the conceptual nature of the CGA. In this study, we conducted a web-based survey to identify essential CGA components by linking International Classification of Functioning, Disability, and Health (ICF) category level 2 items and "not defined/not covered" (nd/nc) items. Healthcare professionals and individuals aged >65 years participated in a two-stage Delphi study. In total, 182 respondents (7 geriatricians, 22 nurses, 20 therapists, and 4 case managers) completed the survey. Sixty-one essential components for CGA were identified, including 55 ICF categories. Additionally, personal factors (i.e., proactiveness) and nd/nc items (i.e., subjective perceptions) were aggregated. The results suggest that the CGA includes objective conditions of intrinsic capacity, functional ability, and environment as well as subjective perceptions and proactiveness toward those conditions. Thus, CGA is not merely expected to assess geriatric syndrome but also to estimate broader concepts, such as interoception, resilience, and quality of life.

Childhood socioeconomic status is associated with psychometric intelligence and microstructural brain development.

Childhood socioeconomic status is robustly associated with various children's cognitive factors and neural mechanisms. Here we show the association of childhood socioeconomic status with psychometric intelligence and mean diffusivity and fractional anisotropy using diffusion tensor imaging at the baseline experiment (N = 285) and longitudinal changes in these metrics after 3.0 ± 0.3 years (N = 223) in a large sample of normal Japanese children (mean age = 11.2 ± 3.1 years). After correcting for confounding factors, cross-sectional and longitudinal analyses show that higher childhood socioeconomic status is associated with greater baseline and baseline to follow-up increase of psychometric intelligence and mean diffusivity in areas around the bilateral fusiform gyrus. These results demonstrate that higher socioeconomic status is associated with higher psychometric intelligence measures and altered microstructural properties in the fusiform gyrus which plays a key role in reading and letter recognition and further augmentation of such tendencies during development. Definitive conclusions regarding the causality of these relationships requires intervention and physiological studies. However, the current findings should be considered when developing and revising policies regarding education.

Arterial Spin Labeling Magnetic Resonance Imaging in the Assessment of Non-Convulsive Status Epilepticus in Alzheimer's Disease: A Report of Two Cases.

BACKGROUND The diagnosis of early non-convulsant status epilepticus (NCSE) can be challenging and can overlap with other critical conditions. Two patients with Alzheimer's disease are reported with clinically suspected NCSE presenting in the emergency setting who were diagnosed using arterial spin-labeling magnetic resonance imaging (ASL-MRI) sequences. CASE REPORT In Case 1, a 69-year-old woman with mild Alzheimer's disease and diabetes presented with acute worsening of cognitive status and fluctuating level of consciousness. In Case 2, a 70-year-old man with mild cognitive impairment due to Alzheimer's disease and hypertension presented with acute loss of consciousness and left hemiparesis, without evidence of hypoglycemia or a hypertensive crisis. In both cases, ASL-MRI perfusion images showed focal cerebral hyperperfusion in the posterior cingulate and parietal associative cortex, which involved neurodegenerative areas associated with epilepsy in early Alzheimer's disease. In both cases, the patients developed generalized tonic-clonic epileptic seizures that lasted for 5 minutes or more, which indicated the emergence of status epilepticus that developed from the initial presentation of NCSE. In both cases, electroencephalogram (EEG) findings confirmed that the seizures were controlled by intravenous administration of antiepileptic drugs. Both patients discharged home from the hospital without recurrence of seizures, between 10-12 days after the onset of symptoms. CONCLUSIONS These two cases have demonstrated that ASL-MRI is feasible as an emergency diagnostic tool in clinically suspected NCSE in patients with Alzheimer's disease.

Assessment of Gait Symmetry in Elderly Women with Low Bone Mineral Density Using a Portable Trunk Accelerometer: A Pilot Study.

BACKGROUND Convincing evidence regarding gait and balance function in elderly women with low bone mineral density (BMD) and/or osteoporosis is limited. In the present study, we aimed to compare the gait characteristics in elderly women with and without low BMD and to analyze plausible parameter(s) for predicting low BMD. MATERIAL AND METHODS We retrospectively analyzed prospectively collected data of 26 consecutive postmenopausal women aged >65 years who were admitted to our geriatric outpatient service. They were assigned to 2 groups, with (n=14) and without (n=12) low BMD based on T-score (0.05). Receiver operating characteristic curve analysis demonstrated that LI can predict low BMD in the femur neck with moderate accuracy (area under the curve=0.75, 95% confidence interval 0.55-0.95; P=0.031). The optimal cut-off value was 17%, with 67% specificity and 86% sensitivity. CONCLUSIONS These results suggest that elderly women with low BMD may walk with asymmetrical trunk movement, but they are able to generate gait patterns similar to healthy peers. The LI may provide valuable quantitative information for preventing fractures in subjects with osteoporosis.

Precision Radiotherapy and Radiation Risk Assessment: How Do We Overcome Radiogenomic Diversity?

Precision medicine is a rapidly developing area that aims to deliver targeted therapies based on individual patient characteristics. However, current radiation treatment is not yet personalized; consequently, there is a critical need for specific patient characteristics of both tumor and normal tissues to be fully incorporated into dose prescription. Furthermore, current risk assessment following environmental, occupational, or accidental exposures to radiation is based on population effects, and does not account for individual diversity underpinning radiosensitivity. The lack of personalized approaches in both radiotherapy and radiation risk assessment resulted in the current situation where a population-based model, effective dose, is being used. In this review article, to stimulate scientific discussion for precision medicine in both radiotherapy and radiation risk assessment, we propose a novel radiological concept and metric - the personalized dose and the personalized risk index - that incorporate individual physiological, lifestyle-related and genomic variations and radiosensitivity, outlining the potential clinical application for precision medicine. We also review on recent progress in both genomics and biobanking research, which is promising for providing novel insights into individual radiosensitivity, and for creating a novel conceptual framework of precision radiotherapy and radiation risk assessment.

Non-invasive three-dimensional power Doppler imaging for the assessment of acute cerebral blood flow alteration in a mouse model of subarachnoid haemorrhage.

We aimed to evaluate the feasibility of a non-invasive method of cerebral blood flow (CBF) measurement using high-frequency power Doppler ultrasound imaging in a mouse model of subarachnoid haemorrhage (SAH). The 3-dimensionally (3D) reconstructed blood flow signals (%vascularity) within the brain volume of the middle cerebral artery territory correlated well with reference parameters, baseline carotid artery blood flow (r2  = 0.52, P < 0.0001) and normalized CBF changes (r2  = 0.74 P < 0.0001). These data suggest that the 3D power Doppler analysis may have the potential for reflecting real-time CBF changes during the acute phase of experimental SAH, which may be applicable to preclinical studies on early brain injury.

MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. METHODS: Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. RESULTS: Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n=12; caudate putamen, n=3; hippocampus, n=1) or multiple lesions (cortex and caudate putamen, n=6; cortex and hippocampus, n=2; cortex, hippocampus and thalamus/hypothalamus, n=3; bilateral cortex, n=2). The mortality rate within 24h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P=0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r2=0.31, P=0.0002). CONCLUSION: Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction.

Application of a tri-axial accelerometry-based portable motion recorder for the quantitative assessment of hippotherapy in children and adolescents with cerebral palsy.

[Purpose] This case series aims to evaluate the effects of hippotherapy on gait and balance ability of children and adolescents with cerebral palsy using quantitative parameters for physical activity. [Subjects and Methods] Three patients with gait disability as a sequela of cerebral palsy (one female and two males; age 5, 12, and 25 years old) were recruited. Participants received hippotherapy for 30 min once a week for 2 years. Gait parameters (step rate, step length, gait speed, mean acceleration, and horizontal/vertical displacement ratio) were measured using a portable motion recorder equipped with a tri-axial accelerometer attached to the waist before and after a 10-m walking test. [Results] There was a significant increase in step length between before and after a single hippotherapy session. Over the course of 2 year intervention, there was a significant increase in step rate, gait speed, step length, and mean acceleration and a significant improvement in horizontal/vertical displacement ratio. [Conclusion] The data suggest that quantitative parameters derived from a portable motion recorder can track both immediate and long-term changes in the walking ability of children and adolescents with cerebral palsy undergoing hippotherapy.

Individual differences in cognitive performance and brain structure in typically developing children.

Individual differences in cognitive patterning is informative in understanding one's cognitive strengths and weaknesses. However, little is known about the difference in brain structures relating to individual differences in cognitive patterning. In this study, we classified typically developing children (n=277; age range, 5-16 years) into subtypes with k-means cluster analysis along with factor index scores using the Wechsler Intelligence Scale for Children (Third Edition). We then applied voxel-based morphometry to investigate whether significant gray-matter-volume differences existed among subtypes of cognitive patterns. Depending on the level of performance and cognitive patterning, we obtained six subtypes. One subtype that generally scored below average showed larger volume in the right middle temporal gyrus than the other five. On the other hand, two subtypes that achieved average levels of performance showed reverse-patterned factor index scores (one scored higher in Verbal Comprehension and Freedom from Distractibility, and the other scored lower in these two factor index scores) and had smaller volume in the right middle temporal gyrus than the other subtypes. From these results, we concluded that cognitive discrepancy was also obvious in typically developing children and that differences in cognitive patterning are represented in brain structure.

Assessment of myocardial metabolic disorder associated with mediastinal radiotherapy for esophageal cancer -a pilot study.

BACKGROUND: To evaluate the dose-effect relations for myocardial metabolic disorders after mediastinal radiotherapy (RT) by performing iodine-123 ß-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy. METHODS: Between 2011 and 2012, we performed I-123 BMIPP scintigraphy for patients with esophageal cancer before and six months after curative mediastinal RT. Single photon emission computed tomography (SPECT) images of pre-RT and post-RT were registered into RT dose distributions. The myocardium was contoured, and the regional RT dose was calculated. Normalization is required to compare pre- and post-RT SPECT images because the uptake pattern is changed due to the breathing level. Normalization was applied on the mean of SPECT counts in regions of the myocardium receiving less than 5 Gy. Relative values in each dose region (interval of 5 Gy) were calculated on the basis of this normalization for each patient. The reduction in the percent of relative values was calculated. RESULTS: Five patients were enrolled in this study. None of the patients had a past history of cardiac disease. The left ventricle was partially involved in RT fields in all patients. The patients received RT with median total doses of 60-66 Gy for the primary tumor and metastatic lymph nodes. Concomitant chemotherapy consisting of cisplatin or nedaplatin and 5-fluorouracil with RT was performed in 4 patients. All patients had reduced uptake corresponding to RT fields. Dose-effect relations for reduced uptake tended to be observed at 6 months after RT with mean decreases of 8.96% in regions at 10-15 Gy, 12.6% in regions at 20-25 Gy, 15.6% in regions at 30-35 Gy, 19.0% in regions at 40-45 Gy and 16.0% in regions at 50-55 Gy. CONCLUSIONS: Dose-effect relations for myocardial metabolic disorders tended to be observed. We may need to make an effort to reduce high-dose mediastinal RT to the myocardium in RT planning.

Association between gray matter volume in the caudate nucleus and financial extravagance: findings from voxel-based morphometry.

Consumer behavior differs among individuals; one such common individual difference is financial extravagance. Recent research suggests that the activation of the caudate nucleus plays an important role in consumer behavior. However, to the best of our knowledge, no study has investigated the specific relationship between the caudate nucleus and consumer financial extravagance. Therefore, in this study, we investigated the association between individual differences in financial extravagance and regional gray matter volume in the caudate nucleus by using voxel-based morphometry (VBM). We recruited 776 healthy, right-handed individuals (432 men and 344 women; mean age=20.7 ± 1.8) and used voxel-based morphometry and a financial extravagance questionnaire to determine the association between financial extravagance and gray matter structure in the caudate nucleus. Our measure of financial extravagance was based on the novelty seeking subscales of the Japanese version of the Temperament and Character Inventory. A multiple regression analysis including financial extravagance, age, sex, Raven's Advanced Progressive Matrix score, total intracranial volume, and novelty seeking subscales was conducted to examine what variables were related to regional gray matter volume in the region of interest within the caudate nucleus. A significant positive correlation was found between the obtained financial extravagance score and regional gray matter volume in the caudate nucleus. We found that structural variations in the caudate nucleus contributed to individual differences in financial extravagance. This finding may provide a new neuroscientific approach to understanding individual characteristics of consumers.