Objectives
We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD).
Methods
...Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity.
Results
Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (
P
< 0.00058). Vic and OD in the SNpc and putamen showed significant negative correlations (
P
< 0.05) with disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83).
Conclusion
NODDI is likely to be useful for diagnosing PD and assessing its progression.
Key Points
•
Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique
•
NODDI estimates neurite microstructure more specifically than diffusion tensor imaging
•
By using NODDI, nigrostriatal alterations in PD can be evaluated in vivo
•
NOODI is useful for diagnosing PD and assessing its disease progression
Purpose
The reproducibility of neurite orientation dispersion and density imaging (NODDI) metrics in the human brain has not been explored across different magnetic resonance (MR) scanners from ...different vendors. This study aimed to evaluate the scan–rescan and inter-vendor reproducibility of NODDI metrics in white and gray matter of healthy subjects using two 3-T MR scanners from two vendors.
Methods
Ten healthy subjects (7 males; mean age 30 ± 7 years, range 23–37 years) were included in the study. Whole-brain diffusion-weighted imaging was performed with b-values of 1000 and 2000 s/mm
2
using two 3-T MR scanners from two different vendors. Automatic extraction of the region of interest was performed to obtain NODDI metrics for whole and localized areas of white and gray matter. The coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were calculated to assess the scan–rescan and inter-vendor reproducibilities of NODDI metrics.
Results
The scan–rescan and inter-vendor reproducibility of NODDI metrics (intracellular volume fraction and orientation dispersion index) were comparable with those of diffusion tensor imaging (DTI) metrics. However, the inter-vendor reproducibilities of NODDI (CoV = 2.3–14%) were lower than the scan–rescan reproducibility (CoV: scanner A = 0.8–3.8%; scanner B = 0.8–2.6%). Compared with the finding of DTI metrics, the reproducibility of NODDI metrics was lower in white matter and higher in gray matter.
Conclusion
The lower inter-vendor reproducibility of NODDI in some brain regions indicates that data acquired from different MRI scanners should be carefully interpreted.
BACKGROUND AND PURPOSE―Microstructural damage in the brain induced by chronic ischemia is suggested to play a pivotal role in the neurocognitive dysfunction of adults with Moyamoya disease (MMD). We ...investigated specific changes in the brain microstructure and their correlations with neurocognitive dysfunction in patients with MMD using a multishell diffusion magnetic resonance imaging technique called neurite orientation dispersion and density imaging.
METHODS—We evaluated 26 patients with MMD (16–63 years old, 20 females) and 20 age- and sex-matched normal volunteers using neurite orientation dispersion and density imaging and neuropsychological batteries. Neurite orientation dispersion and density imaging calculates 2 parametersthe intracellular volume fraction (Vic), which reflects the axon density in the white matter and dendrite density in the cortex, and the orientation dispersion index (OD), which reflects the network complexity. The microstructural damage and its correlation with neurocognitive performance were evaluated by performing a whole-brain analysis using SPM12 and correlation analysis with regional values.
RESULTS—Patients with MMD had significantly lower Vic in the white matter and a lower OD mainly in the cortex than those of the controls (P<0.001, family-wise error corrected). Of all neuropsychological scores, Processing Speed Index (PS) exhibited the strongest correlation with Vic in the white matter (P<0.001, family-wise error corrected). The Vic and OD values for regions with group differences, including both temporoparietal and frontal areas, correlated with neurocognitive performance (absolute r=0.37–0.64; P<0.01).
CONCLUSIONS—Chronic ischemia in MMD may decrease the axon density in the white matter and dendrite density in the cortex (Vic) and simplify network complexity (OD), leading to neurocognitive dysfunction. Processing Speed Index may be the most sensitive index used to evaluate the ischemic burden, and the posterior part of the brain may play an important role in neurocognitive function.
CLINICAL TRIAL REGISTRATION—URLhttp://www.umin.ac.jp/ctr/. Unique identifierUMIN000023082.
Medial meniscal extrusion (MME) is associated with progression of medial knee osteoarthritis (OA), but no or little information is available for relationships between MME and osteophytes, which are ...found in cartilage and bone parts. Because of the limitation in detectability of the cartilage part of osteophytes by radiography or conventional magnetic resonance imaging (MRI), the rate of development and size of osteophytes appear to have been underestimated. Because T2 mapping MRI may enable us to evaluate the cartilage part of osteophytes, we aimed to examine the association between MME and OA-related changes, including osteophytes, by using conventional and T2 mapping MRI.
Patients with early-stage knee OA (n = 50) were examined. MRI-detected OA-related changes, in addition to MME, were evaluated according to the Whole-Organ Magnetic Resonance Imaging Score. T2 values of the medial meniscus and osteophytes were measured on T2 mapping images. Osteophytes surgically removed from patients with end-stage knee OA were histologically analyzed and compared with findings derived by radiography and MRI.
Medial side osteophytes were detected by T2 mapping MRI in 98% of patients with early-stage knee OA, although the detection rate was 48% by conventional MRI and 40% by radiography. Among the OA-related changes, medial tibial osteophyte distance was most closely associated with MME, as determined by multiple logistic regression analysis, in the patients with early-stage knee OA (β = 0.711, p < 0.001). T2 values of the medial meniscus were directly correlated with MME in patients with early-stage knee OA, who showed ≥ 3 mm of MME (r = 0.58, p = 0.003). The accuracy of osteophyte evaluation by T2 mapping MRI was confirmed by histological analysis of the osteophytes removed from patients with end-stage knee OA.
Our study demonstrates that medial tibial osteophyte evaluated by T2 mapping MRI is frequently observed in the patients with early-stage knee OA, showing close association with MME, and that MME is positively correlated with the meniscal degeneration.
Early hepatocyte death occurs in most liver injury cases and triggers liver inflammation, which in combination with other risk factors leads to the development of liver disease. However, the ...pathogenesis of early phase hepatocyte death remains poorly understood. Here, C57BL/6J mice were treated with the hepatotoxic drug flucloxacillin (FLUX) and the toll-like receptor 9 agonist CpG oligodeoxynucleotide (ODN) to reproduce the early phase of drug-induced hepatotoxicity and investigate its pathogenesis. C57BL/6J mice were treated with FLUX (100 mg/kg, gavage) alone or in combination with ODN (40 μg/mouse, intraperitoneally). Plasma alanine aminotransferase (ALT) level was measured as a marker of hepatotoxicity. FLUX or ODN alone was insufficient to induce ALT elevation, whereas combination treatment with FLUX and ODN increased ALT levels 24 h after FLUX treatment and upregulated Fas ligand in natural killer T (NKT) cells and Fas in hepatocytes. FLUX induced mitochondrial permeability transition (MPT), and pretreatment with ODN sensitized mitochondria to FLUX-induced MPT. The increase in ALT levels induced by ODN and FLUX co-treatment was suppressed in Fas ligand (
gld/gld
)-deficient mice and in mice deficient in a component of MPT pore opening (cyclophilin D-knockout mice). These results suggested that ODN activated the Fas/Fas ligand-mediated pathway in NKT cells and hepatocytes, which may predispose to FLUX-induced mitochondrial dysfunction and lead to early phase hepatocyte apoptosis. Taken together, these findings elucidate a potentially novel mechanism underlying drug-induced early phase hepatocyte death related to the Fas/Fas ligand death receptor pathway and mitochondrial dysfunction.
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.
Most cancer cells predominantly produce energy by glycolysis, even in the presence of adequate oxygen. Therefore, inhibition of glycolysis is a promising cancer treatment target. Recently, it has ...been recognized that to conduct thorough treatment of cancer, comprehensive understanding of cancer metabolism is essential, not only focusing on glycolysis. Here, we investigated the supporting mechanism of autophagy, which is a catabolic process that recycles intracellular components, for energy supply in the glycolysis-inhibited condition. Autophagy is thought to be highly activated in cancers and to promote their growth or progression by adapting to the harsh surrounding microenvironment. We found that cancer cells positively promoted autophagy to overcome the energy shortage from glycolysis by maintaining mitochondrial activity for ATP production essential for survival. Conclusively, autophagy plays a role in determining whether cancer cells live or die, and autophagic ability in cancer cells is a promising target for therapy.
•Autophagy is enhanced by suppression of glycolytic energy supply.•Autophagy becomes a driving force of oxidative phosphorylation.•Autophagy supports cancer cell survival by maintaining mitochondrial function.
Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, ...the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65-84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 reference, Medium; 1.53 95% confidence interval (CI) 0.94-2.48, Low; 1.86 1.02-3.39, p for trend 0.047) and reduced muscle strength (High; 1.00 reference, Medium; 1.40 0.98-2.02, Low; 1.49 1.04-2.15, p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64-11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk.
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