Explore the vast range of titles available.

PurposeThe diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was developed to evaluate the brain’s glymphatic function or interstitial fluid dynamics. This study aimed to evaluate the reproducibility of the DTI-ALPS method and the effect of modifications in the imaging method and data evaluation.Materials and methodsSeven healthy volunteers were enrolled in this study. Image acquisition was performed for this test–retest study using a fixed imaging sequence and modified imaging methods which included the placement of region of interest (ROI), imaging plane, head position, averaging, number of motion-proving gradients, echo time (TE), and a different scanner. The ALPS-index values were evaluated for the change of conditions listed above.ResultsThis test–retest study by a fixed imaging sequence showed very high reproducibility (intraclass coefficient = 0.828) for the ALPS-index value. The bilateral ROI placement showed higher reproducibility. The number of averaging and the difference of the scanner did not influence the ALPS-index values. However, modification of the imaging plane and head position impaired reproducibility, and the number of motion-proving gradients affected the ALPS-index value. The ALPS-index values from 12-axis DTI and 3-axis diffusion-weighted image (DWI) showed good correlation (r = 0.86). Also, a shorter TE resulted in a larger value of the ALPS-index.ConclusionALPS index was robust under the fixed imaging method even when different scanners were used. ALPS index was influenced by the imaging plane, the number of motion-proving gradient axes, and TE in the imaging sequence. These factors should be uniformed in the planning ALPS method studies. The possibility to develop a 3-axis DWI-ALPS method using three axes of the motion-proving gradient was also suggested.

Most cancer cells rely on glycolysis to generate ATP, even when oxygen is available. However, merely inhibiting the glycolysis is insufficient for the eradication of cancer cells. One main reason for this is that cancer cells have the potential to adapt their metabolism to their environmental conditions. In this study, we investigated how cancer cells modify their intracellular metabolism when glycolysis is suppressed, using PANC-1 pancreatic cancer cells and two other solid tumor cell lines, A549 and HeLa. Our study revealed that glycolytically suppressed cells upregulated mitochondrial function and relied on oxidative phosphorylation (OXPHOS) to obtain the ATP necessary for their survival. Dynamic changes in intracellular metabolic profiles were also observed, reflected by the reduced levels of TCA cycle intermediates and elevated levels of most amino acids. Glutamine and glutamate were important for this metabolic reprogramming, as these were largely consumed by influx into the TCA cycle when the glycolytic pathway was suppressed. During the reprogramming process, activated autophagy was involved in modulating mitochondrial function. We conclude that upon glycolytic suppression in multiple types of tumor cells, intracellular energy metabolism is reprogrammed toward mitochondrial OXPHOS in an autophagy-dependent manner to ensure cellular survival.

A bstract In the DsTau experiment at the CERN SPS (NA65), an independent and direct way to measure tau neutrino production following high energy proton interactions was proposed. As the main source of tau neutrinos is a decay of D s mesons, produced in proton-nucleus interactions, the project aims at measuring a differential cross section of this reaction. The experimental method is based on a use of high resolution emulsion detectors for effective registration of events with short lived particle decays. Here we present the motivation of the study, details of the experimental technique, and the first results of the analysis of the data collected during test runs, which prove feasibility of the full scale study of the process in future.

Inhibiting prepotent responses in the face of external stop signals requires complex information processing, from perceptual to control processing. However, the cerebral circuits underlying these processes remain elusive. In this study, we used neuroimaging and brain stimulation to investigate the interplay between human brain regions during response inhibition at the whole-brain level. Magnetic resonance imaging suggested a sequential four-step processing pathway: initiating from the primary visual cortex (V1), progressing to the dorsal anterior insula (daINS), then involving two essential regions in the inferior frontal cortex (IFC), namely the ventral posterior IFC (vpIFC) and anterior IFC (aIFC), and reaching the basal ganglia (BG)/primary motor cortex (M1). A combination of ultrasound stimulation and time-resolved magnetic stimulation elucidated the causal influence of daINS on vpIFC and the unidirectional dependence of aIFC on vpIFC. These results unveil asymmetric pathways in the insular - prefrontal cortex and outline the macroscopic cerebral circuits for response inhibition: V1→daINS→vpIFC/aIFC→BG/M1. Osada et al. used MRI and brain stimulation to outline the macroscopic cerebral circuits for response inhibition: visual cortex→dorsal anterior insula→inferior frontal cortex→basal ganglia/motor cortex, confirming the insula’s critical bridging role.

•We evaluated gray and white matter microstructure alterations using diffusion kurtosis imaging, free-water imaging, and neurite orientation dispersion and density imaging, in 28 patients with euthymic BD and 28 healthy controls.•We detected microstructure alterations in wide areas of white matter and gray matter in patients with BD.•In BD, cognitive function was correlated with gray matter microstructure alterations, reflected by increased extracellular FW in relevant brain areas, more strongly than with white matter impairment according to decreased FA. Bipolar disorder (BD) is a chronic mental disorder involving cognitive dysfunction. Imaging studies reveal reduced cortical thickness and impaired white matter integrity in BD; however, the biological pathophysiology underlying cognitive dysfunctions remains unclear. In 28 patients with euthymic BD and 28 healthy controls, we evaluated gray and white matter microstructure alterations using diffusion kurtosis imaging, free-water imaging, and neurite orientation dispersion and density imaging. We detected microstructure alterations using tract-based spatial statistics (TBSS) analysis and gray matter-based spatial statistics (GBSS). Voxel-wise analysis was performed to evaluate associations between microstructure alterations and cognitive performance measured by WAIS-IV. Compared to healthy controls, BD patients exhibited decreased fractional anisotropy (FA) and free-water (FW)-corrected FA, along with mean diffusivity (MD) and radial diffusivity (RD) across a wide area on TBSS. BD patients showed increased diffusion tensor imaging (DTI) indices, accompanied by increased isotropic volume fraction (ISOVF) and free-water (FW) in the frontal, temporal, parietal, and limbic areas on GBSS. The working memory index was negatively correlated with FW in the right hemisphere of the posterior corona radiata, and processing speed index was negatively correlated with FW in the bilateral isthmus of the cingulate gyrus, bilateral cerebellum cortex, parahippocampal gyrus, left hemisphere entorhinal cortex, and precuneus. Cognitive performance showed negligible correlations with DTI indices. In BD, cognitive function was correlated with gray matter microstructure alterations, reflected by increased extracellular FW in relevant brain areas, more strongly than with white matter impairment according to decreased FA.

Despite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells.

PurposeThis study aimed to evaluate the relationship between sleep quality as assessed using the Pittsburgh Sleep Quality Index (PSQI) and the index of diffusivity along the perivascular space (ALPS index), a possible indirect indicator of glymphatic system activity.Materials and methodsThis study included the diffusion magnetic resonance imaging (MRI) data of 317 people with sleep disruption and 515 healthy controls (HCs) from the Human Connectome Project (WU-MINN HCP 1200). The ALPS index was calculated automatically based on diffusion tensor image analysis (DTI)-ALPS of diffusion MRI. The ALPS index of the sleep disruption and HC groups was compared using general linear model (GLM) analysis with covariates, such as age, sex, level of education, and intracranial volume. In addition, to confirm the relationship between sleep quality and the ALPS index in the sleep disruption group as well as evaluate the effect of each PSQI component on the ALPS index, correlation analyses between the ALPS indices and PSQI scores of all the components and between the ALPS index and each PSQI component was performed using GLM analysis with the abovementioned covariates, respectively.ResultsThe ALPS index was significantly lower in the sleep disruption group than in the HC group (p = 0.001). Moreover, the ALPS indices showed significant negative correlations with the PSQI scores of all the components (false discovery rate [FDR]-corrected p < 0.001). Two significant negative correlations were also found between the ALPS index and PSQI component 2 (sleep latency, FDR-corrected p < 0.001) and 6 (the use of sleep medication, FDR-corrected p < 0.001).ConclusionOur findings suggest that glymphatic system impairment contributes to sleep disruption in young adults.

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

Hypertension and diabetes are prevalent among older people and may be associated with cancer. Although several network analyses have been conducted to visualize the associations between diseases and relevant factors, to the best of our knowledge, none have focused on visualizing the associations between cancer and other diseases. We conducted a network analysis to explore the associations between cancer, hypertension, and diabetes. This study used a large-scale clinical dataset of 1,026,305 hospitalized patients aged ≥ 65 years, collected between April 2008 and December 2020. Diseases were categorized using the International Classification of Diseases-10 (2019 version) codes. The analysis focused on diseases with a prevalence of ≥ 1%. A multimorbidity network was constructed for the entire patient cohort, and the same analysis was applied specifically to cancer patients. Hypertension (degree centrality: 58/61) and diabetes (degree centrality: 56/61) were connected to several diseases, indicating significant multimorbidity in the cohort. The associations (observed-to-expected ratio) between digestive system cancers and hypertension and diabetes were relatively stronger than those between the diseases and other cancers. Type 2 diabetes and essential hypertension may be risk factors of cancers at multiple digestive system sites. Early treatment of these conditions could prevent or delay the progression of digestive system cancers.

Magnetization transfer (MT) imaging has been widely used for estimating myelin content in the brain. Recently, two other approaches, namely simultaneous tissue relaxometry of R 1 and R 2 relaxation rates and proton density (SyMRI) and the ratio of T 1 -weighted to T 2 -weighted images (T 1 w/T 2 w ratio), were also proposed as methods for measuring myelin. SyMRI and MT imaging have been reported to correlate well with actual myelin by histology. However, for T 1 w/T 2 w ratio, such evidence is limited. In 20 healthy adults, we examined the correlation between these three methods, using MT saturation index (MT sat ) for MT imaging. After calibration, white matter (WM) to gray matter (GM) contrast was the highest for SyMRI among these three metrics. Even though SyMRI and MT sat showed strong correlation in the WM (r = 0.72), only weak correlation was found between T 1 w/T 2 w and SyMRI (r = 0.45) or MT sat (r = 0.38) (correlation coefficients significantly different from each other, with p values < 0.001). In subcortical and cortical GM, these measurements showed moderate to strong correlations to each other (r = 0.54 to 0.78). In conclusion, the high correlation between SyMRI and MT sat indicates that both methods are similarly suited to measure myelin in the WM, whereas T 1 w/T 2 w ratio may be less optimal.