XCR1+ conventional dendritic cell-induced CD4+ T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury.

Cardiac remodeling has no established therapies targeting inflammation. CD4+ T-cell subsets have been reported to play significant roles in healing process after ischemic myocardial injury, but their detailed mechanisms of activation remain unknown. To explore immune reactions during cardiac remodeling, we applied a non-surgical model of coronary heart disease (CHD) induced by a high-fat diet (HFD-CHD) in SR-BI-/-/ApoeR61h/h mice. Flow cytometry analyses throughout the period of progressive cardiac dysfunction revealed that CD4+ T Helper 1 (Th1) cells were predominantly activated in T-cell subsets. Probucol was reported to attenuate cardiac dysfunction after coronary artery ligation model (ligation-MI) in rats. To determine whether probucol suppress cardiac remodeling after HFD-CHD, we treated SR-BI-/-/ApoeR61h/h mice with probucol. We found treatment with probucol in HFD-CHD mice reduced cardiac dysfunction, with attenuated activation of Th1 cells. RNA-seq analyses revealed that probucol suppressed the expression of CXCR3, a Th1-related chemokine receptor, in the heart. XCR1+ cDC1 cells, which highly expresses the CXCR3 ligands CXCL9 and CXCL10, were predominantly activated after HFD-CHD. XCR1+ cDC1 lineage skewing of pre-DC progenitors was observed in bone marrow, with subsequent systemic expansion of XCR1+ cDC1 cells after HFD-CHD. Activation of CXCR3+ Th1 cell and XCR1+ cDC1 cells was also observed in ligation-MI. Notably, post-MI depletion of XCR1+ cDC1 cells suppressed CXCR3+ Th1 cell activation and prevented cardiac dysfunction. In patient autopsy samples, CXCR3+ Th1 and XCR1+ cDC1 cells infiltrated the infarcted area. In this study, we identified a critical role of XCR1+ cDC1-activated CXCR3+ Th1 cells in ischemic cardiac remodeling.

AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170.

AMP-activated protein kinase (AMPK) is a multifunctional kinase that regulates microtubule (MT) dynamic instability through CLIP-170 phosphorylation; however, its physiological relevance in vivo remains to be elucidated. In this study, we identified an active form of AMPK localized at the intercalated disks in the heart, a specific cell-cell junction present between cardiomyocytes. A contractile inhibitor, MYK-461, prevented the localization of AMPK at the intercalated disks, and the effect was reversed by the removal of MYK-461, suggesting that the localization of AMPK is regulated by mechanical stress. Time-lapse imaging analysis revealed that the inhibition of CLIP-170 Ser-311 phosphorylation by AMPK leads to the accumulation of MTs at the intercalated disks. Interestingly, MYK-461 increased the individual cell area of cardiomyocytes in CLIP-170 phosphorylation-dependent manner. Moreover, heart-specific CLIP-170 S311A transgenic mice demonstrated elongation of cardiomyocytes along with accumulated MTs, leading to progressive decline in cardiac contraction. In conclusion, these findings suggest that AMPK regulates the cell shape and aspect ratio of cardiomyocytes by modulating the turnover of MTs through homeostatic phosphorylation of CLIP-170 at the intercalated disks.

Quantitative Susceptibility Mapping and Amide Proton Transfer-Chemical Exchange Saturation Transfer for the Evaluation of Intracerebral Hemorrhage Model.

This study aimed to evaluate an intracerebral hemorrhage (ICH) model using quantitative susceptibility mapping (QSM) and chemical exchange saturation transfer (CEST) with preclinical 7T-magnetic resonance imaging (MRI) and determine the potential of amide proton transfer-CEST (APT-CEST) for use as a biomarker for the early detection of ICH. Six Wistar male rats underwent MRI, and another six underwent histopathological examinations on postoperative days 0, 3, and 7. The ICH model was created by injecting bacterial collagenase into the right hemisphere of the brain. QSM and APT-CEST MRI were performed using horizontal 7T-MRI. Histological studies were performed to observe ICH and detect iron deposition at the ICH site. T2-weighted images (T2WI) revealed signal changes associated with hemoglobin degeneration in red blood cells, indicating acute-phase hemorrhage on day 0, late-subacute-phase hemorrhage on day 3, and chronic-phase hemorrhage on day 7. The susceptibility alterations in each phase were detected using QSM. QSM and Berlin blue staining revealed hemosiderin deposition in the chronic phase. APT-CEST revealed high magnetization transfer ratios in the acute phase. Abundant mobile proteins and peptides were observed in early ICH, which were subsequently diluted. APT-CEST imaging may be a reliable noninvasive biomarker for the early diagnosis of ICH.

Evaluation of the efficacy of creatine chemical exchange saturation transfer imaging in assessing testicular maturity.

Purpose: Microscopic testicular sperm extraction is the most effective treatment for NOA, but the sperm retrieval rate is low and depends on testicular maturity. However, there are limited useful tests to assess testicular maturity. Chemical exchange saturation transfer (CEST) imaging is a new magnetic resonance imaging (MRI) technique that can image the distribution of trace substances in vivo. We focused on the potential role of creatine (Cr) in testes and hypothesized that Cr-CEST could indicate intratesticular spermatogenesis. Methods: We performed Cr-CEST by using 7T MRI on wild-type C57B6/J mice and several types of male infertility models such as Sertoli-cell only (SCO) (Kitw/Kitwv), maturation arrest (MA) (Zfp541 knockout mouse and Kctd19 knockout mouse), and teratozoospermia (Tbc1d21 knockout mouse). After performing Cr-CEST, histological analysis was performed. Results: The SCO and MA models showed decreased CEST signal intensity (p < 0.05), while no reduction was observed in the teratozoospermia model (p = 1.0). CEST signal intensity increased as the spermatogenesis stage progressed from the SCO model to the MA and teratozoospermia models. Furthermore, CEST signal intensity was reduced in 4-week-old wild-type mice with immature testes (p < 0.05). Conclusions: This study suggests that Cr-CEST evaluates intratesticular spermatogenesis noninvasively and provides a new therapeutic strategy for treating male infertility.

Evaluation of right coronary vascular dysfunction in severe pulmonary hypertensive rats using synchrotron radiation microangiography.

Pulmonary hypertension (PH) causes cardiac hypertrophy in the right ventricle (RV) and eventually leads to RV failure due to persistently elevated ventricular afterload. We hypothesized that the mechanical stress on the RV associated with increased afterload impairs vasodilator function of the right coronary artery (RCA) in PH. Coronary vascular response was assessed using microangiography with synchrotron radiation (SR) in two well-established PH rat models, monocrotaline injection or the combined exposure to chronic hypoxia and vascular endothelial growth factor receptor blockade with Su5416 (SuHx model). In the SuHx model, the effect of the treatment with the nonselective endothelin-1 receptor antagonist (ERA), macitentan, was also examined. Myocardial viability was determined in SuHx model rats, using 18F-FDG Positron emission tomography (PET) and magnetic resonance imaging (MRI). Endothelium-dependent and endothelium-independent vasodilator responses were significantly attenuated in the medium and small arteries of severe PH rats. ERA treatment significantly improved RCA vascular function compared with the untreated group. ERA treatment improved both the decrease in ejection fraction and the increased glucose uptake, and reduced RV remodeling. In addition, the upregulation of inflammatory genes in the RV was almost suppressed by ERA treatment. We found impairment of vasodilator responses in the RCA of severe PH rat models. Endothelin-1 activation in the RCA plays a major role in impaired vascular function in PH rats and is partially restored by ERA treatment. Treatment of PH with ERA may improve RV function in part by indirectly attenuating right heart afterload and in part by associated improvements in right coronary endothelial function.NEW & NOTEWORTHY We demonstrated for the first time the impairment of vascular responses in the right coronary artery (RCA) of the dysfunctional right heart in pulmonary hypertensive rats in vivo. Treatment with an endothelin-1 receptor antagonist ameliorated vascular dysfunction in the RCA, enabled tissue remodeling of the right heart, and improved cardiac function. Our results suggest that impaired RCA function might also contribute to the early progression to heart failure in patients with severe pulmonary arterial hypertension (PAH). The endothelium of the coronary vasculature might be considered as a potential target in treatments to prevent heart failure in severe patients with PAH.

Accurate Estimation of the Duration of Testicular Ischemia Using Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging.

BACKGROUND: In the management of testicular torsion, estimating the duration of testicular ischemia is essential for deciding on an appropriate surgical treatment, but there are currently limited evaluation methods. PURPOSE: To perform testicular creatine chemical exchange saturation transfer (CrCEST) imaging and to evaluate its ability to accurately estimate the duration of testicular ischemia. STUDY TYPE: Prospective. ANIMAL MODEL: C57BL/6 control mice (n = 6) and testicular ischemia models induced by clamping the spermatic cord (n = 14). Eight of testicular ischemia models were serially imaged at two or three timepoints and a total of 26 images of ischemic testis were obtained. The ischemic duration ranged from 6-42 hours. FIELD STRENGTH/SEQUENCE: 11.7T vertical-bore MRI/segment fast low-angle shot acquisition for CEST. ASSESSMENT: CrCEST imaging was performed and the magnetization transfer ratio for the CrCEST effect (MTRCr** ) was calculated in control mice and testicular ischemia models. Correlation analysis between the duration of testicular ischemia and MTRCr** decline was performed. STATISTICAL TESTS: Paired t-test, and Pearson's correlation analysis. RESULTS: In control mice, the CrCEST effect in testes was significantly more than five times higher than that in skeletal muscle. MTRCr** did not differ significantly between the right and left testes (8.6 ± 0.8 vs. 8.3 ± 0.6, P = 0.96). In testicular ischemia models, MTRCr** of ischemic testes was significantly lower than that of controls (4 ± 2 vs. 8.9 ± 0.6, P < 0.001). Correlation analysis revealed a strong linear correlation between MTRCr** decline and the duration of ischemia (r = 0.96, P < 0.001). DATA CONCLUSION: A decreased CrCEST effect in ischemic testes correlated well with ischemic duration. Testicular CrCEST imaging was useful for accurately estimating the duration of testicular ischemia. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Visualization of Spatial Distribution of Spermatogenesis in Mouse Testes Using Creatine Chemical Exchange Saturation Transfer Imaging.

BACKGROUND: When determining treatment strategies for male infertility, it is important to evaluate spermatogenesis and its spatial distribution in the testes. PURPOSE: To investigate the usefulness of creatine chemical exchange saturation transfer (CrCEST) imaging for evaluating spermatogenesis and its spatial distribution. STUDY TYPE: Prospective. ANIMAL MODEL: C57BL/6 control mice (n = 5) and model mice of male infertility induced by whole testis X-ray irradiation (n = 11) or localized X-ray irradiation to lower regions of testes (n = 3). FIELD STRENGTH/SEQUENCE: A 11.7-T vertical-bore magnetic resonance imaging (MRI)/segmented fast low-angle shot acquisition for CEST. ASSESSMENT: The magnetization transfer ratio for the CrCEST effect (MTRCr* ) was calculated in each testis of the control mice and X-ray irradiation model mice at 10, 15, 20, and 30 days after irradiation. Correlation analysis was performed between MTRCr* and Johnsen's score, a histological score for spermatogenesis. In the localized X-ray irradiation model, regional MTRCr* and Johnsen's score were calculated for correlation analysis. STATISTICAL TESTS: Unpaired t-test, one-way analysis of variance with Tukey's HSD test and Pearson's correlation analysis. A P value < 0.05 was considered statistically significant. RESULTS: In the irradiation model, CrCEST imaging revealed a significant linear decrease of MTRCr* after irradiation (control, 8.7 ± 0.6; 10 days, 7.9 ± 0.8; 15 days, 6.5 ± 0.6; 20 days, 5.4 ± 1.0; 30 days, 4.4 ± 0.8). A significant linear correlation was found between MTRCr* and Johnsen's score (Pearson's correlation coefficient (r) = 0.79). In the localized irradiation model, CrCEST imaging visualized a significant regional decrease of MTRCr* in the unshielded region (shielded, 6.9 ± 0.7; unshielded, 4.9 ± 1.0), and a significant linear correlation was found between regional MTRCr* and Johnsen's score (r = 0.78). DATA CONCLUSION: Testicular CrCEST effects correlated well with spermatogenesis. CrCEST imaging was useful for evaluating spermatogenesis and its spatial distribution. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction.

RATIONALE: Myofibroblasts have roles in tissue repair following damage associated with ischemia, aging, and inflammation and also promote fibrosis and tissue stiffening, causing organ dysfunction. One source of myofibroblasts is mesenchymal stromal/stem cells that exist as resident fibroblasts in multiple tissues. We previously identified meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue), a glycosylphosphatidylinositol-anchored membrane protein, as a specific marker of mesenchymal stromal/stem cells and a regulator of their undifferentiated state. The roles of meflin in the development of heart disease, however, have not been investigated. OBJECTIVE: We examined the expression of meflin in the heart and its involvement in cardiac repair after ischemia, fibrosis, and the development of heart failure. METHODS AND RESULTS: We found that meflin has an inhibitory role in myofibroblast differentiation of cultured mesenchymal stromal/stem cells. Meflin expression was downregulated by stimulation with TGF (transforming growth factor)-ß, substrate stiffness, hypoxia, and aging. Histological analysis revealed that meflin-positive fibroblastic cells and their lineage cells proliferated in the hearts after acute myocardial infarction and pressure-overload heart failure mouse models. Analysis of meflin knockout mice revealed that meflin is essential for the increase in the number of cells that highly express type I collagen in the heart walls after myocardial infarction induction. When subjected to pressure overload by transverse aortic constriction, meflin knockout mice developed marked cardiac interstitial fibrosis with defective compensation mechanisms. Analysis with atomic force microscopy and hemodynamic catheterization revealed that meflin knockout mice developed stiff failing hearts with diastolic dysfunction. Mechanistically, we found that meflin interacts with bone morphogenetic protein 7, an antifibrotic cytokine that counteracts the action of TGF-ß and augments its intracellular signaling. CONCLUSIONS: These data suggested that meflin is involved in cardiac tissue repair after injury and has an inhibitory role in myofibroblast differentiation of cardiac fibroblastic cells and the development of cardiac fibrosis.

Radiomics-Based Machine Learning Classification for Glioma Grading Using Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to evaluate various radiomics-based machine learning classification models using the apparent diffusion coefficient (ADC) and cerebral blood flow (CBF) maps for differentiating between low-grade gliomas (LGGs) and high-grade gliomas (HGGs). METHODS: Fifty-two glioma patients, including 18 LGGs (grade II) and 34 HGGs (grade III/IV), were examined using a 3.0-T magnetic resonance scanner. The ADC and CBF maps were obtained from diffusion-weighted imaging and pseudo-continuous arterial spin labeling perfusion-weighted imaging, respectively. A total of 91 radiomic features were extracted from each of the tumor volume on the ADC and CBF maps. We constructed 4 types of machine learning classifiers based on (1) least absolute shrinkage and selection operator regularized logistic regression (LASSO-LR), (2) random forest (RF), (3) support vector machine (SVM) with the radial basis function kernel (SVM-RBF), and (4) SVM with the linear kernel (SVM-L). A training set with 36 gliomas (70%) was used to select the important radiomic features and train each model using 5-fold cross-validation. The remaining 16 gliomas (30%) were used as a test set. Receiver operating characteristic analysis was performed to evaluate the model performance. RESULTS: A radiomic feature, ADC first-order-based skewness, was selected as an important variable in all classification models. According to the receiver operating characteristic analysis, the areas under the curve of the LASSO-LR, RF, SVM-RBF, and SVM-L models for the training set were 0.965, 1.000, 0.979, and 0.969, respectively. For the test set, the areas under the curve of the LASSO-LR, RF, SVM-RBF, and SVM-L models were 0.883, 0.917, 0.717, and 0.917, respectively. All classification models showed sufficient diagnostic performance on the test set. CONCLUSIONS: Radiomics-based machine learning classifiers using the quantitative ADC and CBF maps are useful for differentiating HGGs from LGGs.

Mouse skeletal muscle creatine chemical exchange saturation transfer (CrCEST) imaging at 11.7T MRI.

BACKGROUND: Creatine chemical exchange saturation transfer (CrCEST) imaging is expected to be a novel evaluation method of muscular energy metabolism. PURPOSE: To develop CrCEST imaging of mouse skeletal muscle and to validate this technique by measuring changes in Cr concentration of ischemic hindlimbs. STUDY TYPE: Prospective. ANIMAL MODEL: C57BL/6 mice (n = 6), mild hindlimb ischemic mice (n = 6), and severe hindlimb ischemic mice (n = 6). FIELD STRENGTH/SEQUENCE: Magnetic resonance angiography (MRA), CrCEST imaging, and phosphorus magnetic resonance spectroscopy (31 P MRS) obtained at 11.7T. ASSESSMENT: MRA and 31 P MRS were performed to confirm the presence of ischemia following the compression by rubber tourniquet. CrCEST imaging was performed and magnetization transfer ratio asymmetry (MTRasym ), which reflects Cr concentration, and was calculated in severe ischemia models, mild ischemia models, and control mice. Follow-up CrCEST imaging was performed after the release of ischemia in the mild ischemia models. STATISTICAL TESTS: Mean ± SD, one-way analysis of variance (ANOVA) with Tukey's HSD test, unpaired or paired t-test. RESULTS: MRA revealed the loss of blood flow of the femoral artery in the ischemic hindlimb. 31 P MRS revealed different degrees of PCr decrease in severe and mild ischemic hindlimb (n = 3 per group, normal hindlimb: 1.0 ± 0, mild ischemic hindlimb: 0.77 ± 0.13, severe ischemic hindlimb: 0 ± 0). CrCEST imaging inversely revealed a significant stepwise increase in the MTRasym ratio of ischemic hindlimbs compared with controls (control, mild ischemia, and severe ischemia; 0.99 ± 0.04, 1.36 ± 0.08, and 1.59 ± 0.23, respectively, P < 0.0001). In addition, follow-up CrCEST imaging after the release of ischemia revealed normalization of the MTRasym ratios (recovered hindlimb: 1.01 ± 0.05). DATA CONCLUSION: We demonstrated an increase in the MTRasym of ischemic hindlimbs, along with a decrease of PCr. We demonstrated the normalization of MTRasym after the release of ischemia and developed CrCEST imaging of mouse skeletal muscle. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:563-570.

Magnetic Resonance Elastography: Measurement of Hepatic Stiffness Using Different Direct Inverse Problem Reconstruction Methods in Healthy Volunteers and Patients with Liver Disease.

The purpose of this study was to compare the mean hepatic stiffness values obtained by the application of two different direct inverse problem reconstruction methods to magnetic resonance elastography (MRE). Thirteen healthy men (23.2±2.1 years) and 16 patients with liver diseases (78.9±4.3 years; 12 men and 4 women) were examined for this study using a 3.0 T-MRI. The healthy volunteers underwent three consecutive scans, two 70-Hz waveform and a 50-Hz waveform scans. On the other hand, the patients with liver disease underwent scanning using the 70-Hz waveform only. The MRE data for each subject was processed twice for calculation of the mean hepatic stiffness (Pa), once using the multiscale direct inversion (MSDI) and once using the multimodel direct inversion (MMDI). There were no significant differences in the mean stiffness values among the scans obtained with two 70-Hz and different waveforms. However, the mean stiffness values obtained with the MSDI technique (with mask: 2895.3±255.8 Pa, without mask: 2940.6±265.4 Pa) were larger than those obtained with the MMDI technique (with mask: 2614.0±242.1 Pa, without mask: 2699.2±273.5 Pa). The reproducibility of measurements obtained using the two techniques was high for both the healthy volunteers [intraclass correlation coefficients (ICCs): 0.840-0.953] and the patients (ICC: 0.830-0.995). These results suggest that knowledge of the characteristics of different direct inversion algorithms is important for longitudinal liver stiffness assessments such as the comparison of different scanners and evaluation of the response to fibrosis therapy.

Evaluation of Image Quality in Three-dimensional Fat-suppressed T1-weighted Images with Fast Acquisition Mode for Upper Abdomen.

We compared the uniformity of fat-suppression and image quality using three-dimensional fat-suppressed T1-weighted gradient-echo sequences that are liver acquisition with volume acceleration (LAVA) and Turbo-LAVA at 3.0T-MRI. The subjects were seven patients with liver disease (mean age, 66.7±8.2 years). The axial slices of two LAVA sequences were used for the comparison of the uniformity of fat-suppression and image quality at a region-of-interest (ROI) of the liver dome, the porta, and the renal hilum. To yield a quantitative measurement of the uniformity of fat suppression, the percentage standard deviation (%SD) was calculated by comparing two sequences. For image signal to noise ratio (SNR), the contrast between the liver and fat (Cliver-fat), and the liver and muscle (Cliver-muscle), the other ROIs were placed in the superficial fat, liver, spleen, pancreas, and muscle. The %SD in Turbo-LAVA (28.1±16.8%) was lower than that in LAVA (41.5±13.4%). The SNRs in Turbo-LAVA (17.8±4.1 [liver], 12.5±3.0 [pancreas], 14.7±1.6 [spleen], 8.2±3.5 [fat]) were lower than those in LAVA (20.9±6.1 [liver], 16.8±4.1 [pancreas], 17.4±2.4 [spleen], 12.0±4.5 [fat]). While, the Cliver-fat in the Turbo-LAVA (0.72±0.06) was significantly higher than that in LAVA (0.59±0.07). Turbo-LAVA sequence offers superior and more homogenous fat-suppression in comparison to LAVA sequence.

Male prevalent enhancement of leftward asymmetric development of the cerebellar cortex in ferrets (Mustela putorius).

The present study was conducted in MRI-based volumetry to characterize the sexual dimorphism of the cerebellum in young adult ferrets. High spatial resolution 3D anatomical MRI at 7-tesla were acquired ex vivo from fixed cerebella of 90-day-old male and female ferrets. The 3D morphology and topology of cerebellar structures were reproduced well by volume-rendered images obtained from MRI. Volume of the whole cerebellum was significantly larger in males than in females. The cerebellar cortex was further divided into five transverse domains: the anterior zone (AZ; lobules I-V), central zone anterior (lobule VI), central zone posterior (CZp; lobule VII), posterior zone (PZ; lobules VIII-IXa) and nodular zone (NZ; lobules IXb -X). Significantly greater volumes in males than in females were detected bilaterally in the AZ, CZp, and NZ, and leftward in PZ. Notably, the significant volume asymmetry was detected leftward in the CZp of males. By asymmetry quotient analysis, the counterclockwise torque asymmetry of the cerebellum was revealed, and it was more striking in males than in females. The present results suggest that sexual dimorphism of the ferret cerebellum is characterized by enhancing the leftward laterality in the CZp in males, forming the distinctive counterclockwise torque asymmetry.

Neurochemistry in shiverer mouse depicted on MR spectroscopy.

PURPOSE: To evaluate the neurochemical changes associated with hypomyelination, especially to clarify whether increased total N-acetylaspartate (tNAA) with decreased choline (Cho) observed in the thalamus of msd mice with the plp1 mutation is a common finding for hypomyelinating disorders. MATERIALS AND METHODS: We performed magnetic resonance imaging (MRI) and proton MR spectroscopy ((1) H-MRS) of the thalamus and cortex of postnatal 12-week shiverer mice devoid of myelin basic protein (mbp), heterozygous and wild-type mice with a 7.0T magnet. Luxol Fast Blue staining and immunohistochemical analysis with anti-Mbp, Gfap, Olig2, and NeuN antibodies were also performed. RESULTS: In the thalamus, decreased Cho and normal tNAA were observed in shiverer mice. In the cortex, tNAA, Cho, and glutamate were decreased in shiverer mice. Histological and immunohistochemical analysis of shiverer mice brains revealed hypomyelination in the thalamus, white matter, and cortex; astrogliosis and an increased number of total oligodendrocytes in the white matter; and a decreased number of neurons in the cortex. CONCLUSION: The reduction of Cho on (1) H-MRS might be a common marker for hypomyelinating disorders. A normal tNAA level in the thalamus of shiverer mice might be explained by the presence of mature oligodendrocytes, which enable neuron-to-oligodendrocyte NAA transport or NAA catabolism.

Preclinical magnetic resonance imaging and spectroscopy in the fields of radiological technology, medical physics, and radiology.

Magnetic resonance imaging (MRI) is an indispensable diagnostic imaging technique used in the clinical setting. MRI is advantageous over X-ray and computed tomography (CT), because the contrast provided depends on differences in the density of various organ tissues. In addition to MRI systems in hospitals, more than 100 systems are used for research purposes in Japan in various fields, including basic scientific research, molecular and clinical investigations, and life science research, such as drug discovery, veterinary medicine, and food testing. For many years, additional preclinical imaging studies have been conducted in basic research in the fields of radiation technology, medical physics, and radiology. The preclinical MRI research includes studies using small-bore and whole-body MRI systems. In this review, we focus on the animal study using small-bore MRI systems as "preclinical MRI". The preclinical MRI can be used to elucidate the pathophysiology of diseases and for translational research. This review will provide an overview of previous preclinical MRI studies such as brain, heart, and liver disease assessments. Also, we provide an overview of the utility of preclinical MRI studies in radiological physics and technology.