Denoising approach with deep learning-based reconstruction for neuromelanin-sensitive MRI: image quality and diagnostic performance

[Purpose]Neuromelanin-sensitive MRI (NM-MRI) has proven useful for diagnosing Parkinson’s disease (PD) by showing reduced signals in the substantia nigra (SN) and locus coeruleus (LC), but requires a long scan time. The aim of this study was to assess the image quality and diagnostic performance of NM-MRI with a shortened scan time using a denoising approach with deep learning-based reconstruction (dDLR).[Materials and methods]We enrolled 22 healthy volunteers, 22 non-PD patients and 22 patients with PD who underwentNM-MRI, and performed manual ROI-based analysis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in ten healthy volunteers were compared among images with a number of excitations (NEX) of 1 (NEX1), NEX1 images with dDLR (NEX1+dDLR) and 5-NEX images (NEX5). Acquisition times for NEX1 and NEX5 were 3 min 12 s and 15 min 58 s, respectively. Diagnostic performances using the contrast ratio (CR) of the SN (CR_SN) and LC (CR_LC) and those by visual assessment for diferentiating PD from non-PD were also compared between NEX1 and NEX1+dDLR.[Results]Image quality analyses revealed that SNRs and CNRs of the SN and LC in NEX1+dDLR were signifcantly higherthan in NEX1, and comparable to those in NEX5. In diagnostic performance analysis, areas under the receiver operating characteristic curve (AUC) using CR_SN and CR_LC of NEX1+dDLR were 0.87 and 0.75, respectively, which had no signifcant diference with those of NEX1. Visual assessment showed improvement of diagnostic performance by applying dDLR.[Conclusion]Image quality for NEX1+dDLR was comparable to that of NEX5. dDLR has the potential to reduce scan time of NM-MRI without degrading image quality. Both 1-NEX NM-MRI with and without dDLR showed high AUCs for diagnosing PD by CR. The results of visual assessment suggest advantages of dDLR. Further tuning of dDLR would be expected to provide clinical merits in diagnosing PD

APOE2 gene therapy reduces amyloid deposition and improves markers of neuroinflammation and neurodegeneration in a mouse model of Alzheimer disease

Epidemiological studies show that individuals who carry the relatively uncommon APOE ε2 allele rarely develop Alzheimer disease, and if they do, they have a later age of onset, milder clinical course, and less severe neuropathological findings than people without this allele. The contrast is especially stark when compared with the major genetic risk factor for Alzheimer disease, APOE ε4, which has an age of onset several decades earlier, a more aggressive clinical course and more severe neuropathological findings, especially in terms of the amount of amyloid deposition. Here, we demonstrate that brain exposure to APOE ε2 via a gene therapy approach, which bathes the entire cortical mantle in the gene product after transduction of the ependyma, reduces Aβ plaque deposition, neurodegenerative synaptic loss, and, remarkably, reduces microglial activation in an APP/PS1 mouse model despite continued expression of human APOE ε4. This result suggests a promising protective effect of exogenous APOE ε2 and reveals a cell nonautonomous effect of the protein on microglial activation, which we show is similar to plaque-associated microglia in the brain of Alzheimer disease patients who inherit APOE ε2. These data increase the potential that an APOE ε2 therapeutic could be effective in Alzheimer disease, even in individuals born with the risky ε4 allele.</p

RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS

Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone–collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.Shimizu Mikito, Shiraishi Naoyuki, Tada Satoru, et al. RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS. Science Advances 9, 686 (2023); https://doi.org/10.1126/sciadv.adg3193

A case study of Sunshine College\u27s policy and administrative dimensions for teaching conversational English to Japanese students

A linear, analytic case study was conducted of Sunshine College, Tokyo, Japan, to analyze the factors responsible for students improving their conversational English skills and to provide evidence for this improvement. The factors analyzed at Sunshine College included the culture (facilities, philosophy, policy and administration), the administrative staff, the faculty, the students, the Sunshine English Language Method and the criteria for evaluating student success. Sources of information included in-house records, testimonies, participant observation, and tape recordings. Major conclusions of the study were that Sunshine was successful because it uses a naturalistic approach to instruction, similar to that described by Krashen in his theory of language acquisition, and that the separate aspects of Sunshine College function successfully as a system to produce the intended outcome: improvement in conversational English language skills in a culture where such skills are rare due to traditional methods of English instruction