Neuro4Neuro: A neural network approach for neural tract segmentation using large-scale population-based diffusion imaging

Subtle changes in white matter (WM) microstructure have been associated with normal aging and neurodegeneration. To study these associations in more detail, it is highly important that the WM tracts can be accurately and reproducibly characterized from brain diffusion MRI. In addition, to enable analysis of WM tracts in large datasets and in clinical practice it is essential to have methodology that is fast and easy to apply. This work therefore presents a new approach for WM tract segmentation: Neuro4Neuro, that is capable of direct extraction of WM tracts from diffusion tensor images using convolutional neural network (CNN). This 3D end-to-end method is trained to segment 25 WM tracts in aging individuals from a large population-based study (N=9752, 1.5T MRI). The proposed method showed good segmentation performance and high reproducibility, i.e., a high spatial agreement (Cohen's kappa, k = 0.72 ~ 0.83) and a low scan-rescan error in tract-specific diffusion measures (e.g., fractional anisotropy: error = 1% ~ 5%). The reproducibility of the proposed method was higher than that of a tractography-based segmentation algorithm, while being orders of magnitude faster (0.5s to segment one tract). In addition, we showed that the method successfully generalizes to diffusion scans from an external dementia dataset (N=58, 3T MRI). In two proof-of-principle experiments, we associated WM microstructure obtained using the proposed method with age in a normal elderly population, and with disease subtypes in a dementia cohort. In concordance with the literature, results showed a widespread reduction of microstructural organization with aging and substantial group-wise microstructure differences between dementia subtypes. In conclusion, we presented a highly reproducible and fast method for WM tract segmentation that has the potential of being used in large-scale studies and clinical practice.Comment: Preprint to be published in NeuroImag

Study pertaining to the preparation status of disaster-emergency/stocked at hospitals and elderly care facilities in Niigata Prefecturefood

本研究では、現在の新潟県の病院と高齢者施設における災害時の非常食・備蓄食の準備状況をアンケート調査し考察した。調査は、2013（平成25）年5 〜6 月、新潟県内の給食施設395 施設（病院128、高齢者施設267）の管理栄養士に回答を依頼し、205 施設（病院71、高齢者施設134）から回答を得た（回収率51.9%）。その結果、災害時における危機管理マニュアルが182 施設（88.8%）で整備されており、非常食・備蓄食は、201 施設（98.0%）とほとんどの施設で備蓄されていた。非常食・備蓄食の備蓄量は、3 日分が最も多く、平均2.4 ± 0.9 日分で、保存期間が3 〜4 年の食品を備蓄している施設が47.2% あった。備蓄食品は、主食が、お粥（レトルト・缶）、アルファ化米、レトルトご飯の順に多く、主菜、副菜が、缶詰、レトルト、フリーズドライの形態で、魚・肉料理や野菜の煮物が多かった。また、主食・主菜だけでなく、野菜や果物などの副菜も備蓄し、1 食分の献立として組み合わされていた。水については、飲料用と調理用に分けて備蓄している施設が多かった。飲料用として平均2.4 ± 1.6 日分、1 人1 日1.8 ± 1.2ℓ となった。非常食・備蓄食および水の保管は、86.1% が施設内に保管しており、更新方法としては、賞味期限内に日常献立や避難訓練時に使用し、入れ替えていることがわかった。また、施設の厨房の熱源は「ガス+ 電気」「ガス+ 電気+ 蒸気」のように複数の熱源を備えている施設が78.5% あった。食材料以外の備えとして、調理用にガスコンロなどの熱源を20.8% の施設が備蓄していた。　以上の結果から、新潟県の病院・高齢者施設における非常食・備蓄食の準備状況が明らかになり、地域防災計画を基に準備が進められていることが明らかになった。また、危機管理マニュアルの見直しを検討している施設が8.3%、非常食の備蓄量が4 〜5 日以上の施設が2.5% あることも明らかになった。これらの施設は、東日本大震災後に見直しを図っていると推察された。Our study involved the distribution of a questionnaire survey designed to assess the preparation status of disaster-emergency/stocked food inventories at the current hospitals and elderly care facilities in Niigata Prefecture.The survey was conducted during the period from May through June 2013, and 205 responses (71hospitals and 134 elderly care facilities) were obtained (the recovery of 51.9%). The result revealed that 182 facilities (88.8%) had compiled crisis-management manuals in preparation for disasters; moreover,201 facilities (98.0%), or nearly all the participating facilities, had prepared emergency/stocked food supplies. Most of the facilities had stocks of food sufficient for three days, with the average amount being sufficient for 2.4±0.9 days. Water was divided into two categories for storage: one for drinking and the other for cooking. The average amount of stocked drinking water was sufficient for 2.4±1.6 days,or 1.8±1.2ℓ per person per day. Furthermore, 78.5% of all the participating facilities used multiple heat sources such as “gas + electricity” or “gas + electricity + steam.”The above results show that the preparation status of food/water storage has been established based on the regional disaster prevention plan of Niigata refecture. It has also been revealed that 8.3% of the participating facilities are discussing the review of their crisis-management manuals

White matter integrity, executive dysfunction, and processing speed in amyotrophic lateral sclerosis

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is characterized by deficits on tests of executive functions however the contribution of processing speed is unknown. By contrast, multiple sclerosis (MS) is a disorder in which slowed processing speed is regarded as the core deficit, however, methodology is often confounded by tasks which depend on motor speed. MRI studies have revealed multi-system cerebral involvement in ALS, with evidence of reduced white matter volume and integrity in predominantly frontotemporal regions. The current study had two aims. Firstly, to investigate whether cognitive impairments in ALS and MS are due to executive dysfunction or slowed processing speed, independent of motor dysfunction. Secondly, to investigate the relationship between specific cognitive impairments and the integrity of distinct white matter tracts in ALS. Twenty-nine ALS patients, twenty-five MS patients, and matched healthy control groups were administered a dual task paradigm and processing speed tasks in which stimulus presentation times were manipulated. In addition background measures of executive functioning, working memory, verbal memory, and language were administered. White matter integrity was investigated using region-of-interest (ROI) and tract based spatial statistics (TBSS) analyses of diffusion MRI data. ALS patients did not show impairments in tests of processing speed, but deficits were revealed in the dual task, as well as background tests of executive functioning, working memory, and verbal memory. MS patients also exhibited deficits in the dual task as well as background tests of executive functioning, working memory, and verbal memory. However, in contrast to ALS patients, a processing speed deficit was also observed in MS. ROI analyses revealed significant differences in fractional anisotropy (FA) and mean diffusivity () between ALS patients and healthy controls. Reduced integrity was observed in the corticospinal tracts and prefrontal and temporal white matter tracts including uncinate fasciculus, inferior longitudinal fasciculus, and regions of the cingulum. Significant differences also emerged in the white matter underlying the superior, medial and inferior frontal gyri, and the temporal gyri. Similar group differences were found in the TBSS analyses; ALS patients displayed prominent changes in the corticospinal tract and corpus callosum as well as extensive changes in prefrontal and temporal tracts and association fibres. Correlations between task performance and ROI parameters revealed that dual task performance was associated with FA in the middle frontal gyrus white matter while letter fluency indices correlated with FA in the corpus callosum and corticospinal tracts. Furthermore, verbal memory performance correlated with FA in the inferior longitudinal fasciculus and working memory performance correlated with in uncinate fasciculus and hippocampal portion of the cingulum. Correlations with TBSS revealed significant associations between letter fluency indices and FA in the corticospinal tracts and anterior corpus callosum. The current study demonstrates that cognitive impairment in ALS is not due to slowed processing speed. Moreover dual task deficits are related to distinct prefrontal tract involvement in ALS, whilst fluency deficits may reflect decreasing callosal integrity. Deficits in working memory and verbal memory are related to white matter changes in fibre bundles connecting prefrontal, temporal, and limbic structures

A High-Speed Congenic Strategy Using First-Wave Male Germ Cells

BACKGROUND: In laboratory mice and rats, congenic breeding is essential for analyzing the genes of interest on specific genetic backgrounds and for analyzing quantitative trait loci. However, in theory it takes about 3-4 years to achieve a strain carrying about 99% of the recipient genome at the tenth backcrossing (N10). Even with marker-assisted selection, the so-called 'speed congenic strategy', it takes more than a year at N4 or N5. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new high-speed congenic system using round spermatids retrieved from immature males (22-25 days of age). We applied the technique to three genetically modified strains of mice: transgenic (TG), knockin (KI) and N-ethyl-N-nitrosourea (ENU)-induced mutants. The donor mice had mixed genetic backgrounds of C57BL/6 (B6):DBA/2 or B6:129 strains. At each generation, males used for backcrossing were selected based on polymorphic marker analysis and their round spermatids were injected into B6 strain oocytes. Backcrossing was repeated until N4 or N5. For the TG and ENU-mutant strains, the N5 generation was achieved on days 188 and 190 and the proportion of B6-homozygous loci was 100% (74 markers) and 97.7% (172/176 markers), respectively. For the KI strain, N4 was achieved on day 151, all the 86 markers being B6-homozygous as early as on day 106 at N3. The carrier males at the final generation were all fertile and propagated the modified genes. Thus, three congenic strains were established through rapid generation turnover between 41 and 44 days. CONCLUSIONS/SIGNIFICANCE: This new high-speed breeding strategy enables us to produce congenic strains within about half a year. It should provide the fastest protocol for precise definition of the phenotypic effects of genes of interest on desired genetic backgrounds

Abnormal White Matter Integrity in Adolescents with Internet Addiction Disorder: A Tract-Based Spatial Statistics Study

Background: Internet addiction disorder (IAD) is currently becoming a serious mental health issue around the globe. Previous studies regarding IAD were mainly focused on associated psychological examinations. However, there are few studies on brain structure and function about IAD. In this study, we used diffusion tensor imaging (DTI) to investigate white matter integrity in adolescents with IAD. Methodology/Principal Findings: Seventeen IAD subjects and sixteen healthy controls without IAD participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA) was performed by tract-based spatial statistics (TBSS) to localize abnormal white matter regions between groups. TBSS demonstrated that IAD had significantly lower FA than controls throughout the brain, including the orbito-frontal white matter, corpus callosum, cingulum, inferior fronto-occipital fasciculus, and corona radiation, internal and external capsules, while exhibiting no areas of higher FA. Volume-of-interest (VOI) analysis was used to detect changes of diffusivity indices in the regions showing FA abnormalities. In most VOIs, FA reductions were caused by an increase in radial diffusivity while no changes in axial diffusivity. Correlation analysis was performed to assess the relationship between FA and behavioral measures within the IAD group. Significantly negative correlations were found between FA values in the left genu of the corpus callosum and the Screen for Child Anxiety Related Emotional Disorders, and between FA values in the left external capsule and the Young’s Internet addiction scale

Phosphatidylinositol-3 kinase-Akt-mammalian target of rapamycin signaling pathway mediates contractility of human endometriotic stromal cells: A promising new target for the treatment of endometriosis-associated fibrosis

Objective: To assess the involvement of phosphatidylinositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) on the extracellular matrix contractility of endometriotic cells. Materials and methods: The effects of wortmannin, LY294002, Akt inhibitor IV, and Ku-0063794 on the contractility of endometriotic cyst stromal cells (ECSCs) were investigated using collagen gel contraction assay. Results: All four inhibitors of PI3K-Akt-mTOR evaluated in the current study significantly inhibited the contractility of ECSCs. Conclusion: The current findings suggest that the PI3K-Akt-mTOR signaling pathway is involved in the development of endometriosis-associated fibrosis. The PI3K-Akt-mTOR signaling pathway is a promising target for the treatment of endometriosis

Altered balance of epidermis-related chemokines in epidermolysis bullosa

Background: Epidennolysis bullosa (EB) is a congenital, refractory skin disease and there are no fundamental treatments. Recently, allogenic cell therapies are beginning to be applied as potential treatments, that are based on the concept that the allogenic cells can migrate into the skin and reconstitute the skin components. Although the mechanisms of cell migration into skin are not fully understood, chemokines are regarded as key factors in recruiting bone marrow-derived cells. Objectives: Our study aims to elucidate the expression of chemokines in the EB patients. Methods: We determined the expression of wound-healing related chemokines in the sera, keratinocytes, and skin tissues of EB patients and compared them to those of healthy volunteers by enzyme-linked immunosorbent assays, quantitative reverse transcription PCR, and immunofluorescence staining. Results: The serum levels of CXCL12 and HMGB1 were found to be significantly elevated in the EB patients. Conversely, the serum levels of CCL21 were found to be lower in the EB patients than in healthy controls. In addition, the serum levels of CXCL12 tended to increase and the serum levels of CCL27 tended to decrease with an increase in the affected body surface areas. To detect the origin of the circulating chemokines, we performed immunofluorescence staining. CCL21, CCL27, HMGB1 and CXCL12 were stained more broadly in the EB patient tissues than those in the control tissues. Conclusions: These results suggest that fluctuations in chemokine levels may contribute in a coordinated way to the wound-healing process and lend clues toward efficient cell therapies for EB