Noninvasive Characterization of Metabolic Changes in Ischemic Stroke Using Z-spectrum-fitted Multiparametric Chemical Exchange Saturation Transfer-weighted Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging (CEST-MRI). METHODS: Three sets of Z-spectrum data with saturation power (B1) values of 1.5, 2.5, and 3.5 µT, respectively, were acquired from 17 patients with ischemic stroke. Multiple contrasts contributing to the Z-spectrum, including fitted amide proton transfer (APTfitted), +2 ppm peak (CEST@2ppm), concomitantly fitted APTfitted and CEST@2ppm (APT&CEST@2ppm), semisolid magnetization transfer contrast (MT), aliphatic nuclear Overhauser effect (NOE), and direct saturation of water (DSW), were fitted with 4 and 5 Lorentzian functions, respectively. The CEST metrics were compared between ischemic lesions and contralateral normal white matter (CNWM), and the correlation between the CEST metrics and the apparent diffusion coefficient (ADC) was assessed. The differences in the Z-spectrum metrics under varied B1 values were also investigated. RESULTS: Ischemic lesions showed increased APTfitted, CEST@2ppm, APT&CEST@2ppm, NOE, and DSW as well as decreased MT. APT&CEST@2ppm, MT, and DSW showed a significant correlation with ADC [APT&CEST@2ppm at the 3 B1 values: R=0.584/0.467/0.551; MT at the 3 B1 values: R=-0.717/-0.695/-0.762 (4-parameter fitting), R=-0.734/-0.711/-0.785 (5-parameter fitting); DSW of 4-/5-parameter fitting: R=0.794/0.811 (2.5 µT), R=0.800/0.790 (3.5 µT)]. However, the asymmetric analysis of amide proton transfer (APTasym) could not differentiate the lesions from CNWM and showed no correlation with ADC. Furthermore, the Z-spectrum contrasts varied with B1. CONCLUSION: The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues.

Application of Neurite Orientation Dispersion and Density Imaging in Assessing Glioma Grades and Cellular Proliferation.

OBJECTIVE: To explore the performance of neurite orientation dispersion and density imaging (NODDI) in grading gliomas and to evaluate the cellular proliferation. METHODS: NODDI and diffusion-weighted imaging were performed on 79 patients with histopathologically proven gliomas. Parameter maps of intracellular volume fraction (ICVF), orientation dispersion index (ODI), and apparent diffusion coefficient (ADC) were calculated. Regions of interest were placed in the most solid part of the tumor. These metrics were normalized to the contralateral normal-appearing white matter and correlated with Ki-67 expression. RESULTS: ICVF and ODI increased as tumor grades increased, whereas ADC decreased with the increase of tumor grades. Significant differences in normalized ICVF and ODI were observed between low-grade gliomas and high-grade gliomas (ICVF: 0.208 ± 0.104 vs. 0.718 ± 0.234; ODI: 0.952 ± 0.428 vs. 1.767 ± 0.636, P < 0.001, respectively) and between grades II and III (ICVF: 0.208 ± 0.104 vs. 0.603 ± 0.253; ODI: 0.952 ± 0.428 vs. 1.762 ± 0.542, P < 0.001, respectively). Normalized ICVF was also significantly different between grades III and IV (0.603 ± 0.253 vs. 0.803 ± 0.182, P = 0.004). Ki-67 labeling index was positively correlated with normalized ICVF and ODI (r = 0.755 and 0.572, P < 0.001, respectively), and negatively correlated with normalized ADC (r = -0.709, P < 0.001). CONCLUSIONS: NODDI is a promising method in grading gliomas and predicting cellular proliferation. These results may be of great significance for the clinical diagnosis and treatment of gliomas.

JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression.

It has recently been shown that JARID2 contributes to the malignant character of solid tumors, such as epithelial-mesenchymal transition in lung and colon cancer cell lines, but its role in leukemia progression is unexplored. In this study, we explored the effect and underlying molecular mechanism of JARID2 on leukemia cell proliferation. Real-time PCR and Western assay were carried out to detect JARID2 and CCND1 expression. Cell number and cell cycle change were detected using hemocytometer and flow cytometry, and a ChIP assay was utilized to investigate JARID2 and H3K27me3 enrichment on the CCND1 promoter. JARID2 is down-regulated in B-chronic lymphocytic leukemia (B-CLL) and acute monocytic leukemia (AMOL), and knockdown of JARID2 promotes leukemia cell proliferation via acceleration of the G1/S transition. Conversely, ectopic expression of JARID2 inhibits these malignant phenotypes. Mechanistic studies show that JARID2 negatively regulates CCND1 expression by increasing H3K27 trimethylation on the CCND1 promoter. Our findings indicate that JARID2 is a negative regulator of leukemia cell proliferation, and functions as potential tumor suppressor in leukemia.

Methylenetetrahydrofolate reductase polymorphisms and susceptibility to acute lymphoblastic leukemia in a Chinese population: a meta-analysis.

BACKGROUND: Although many epidemiologic studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their association with acute lymphoblastic leukemia (ALL), definitive conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of ALL, a meta-analysis was performed in a Chinese population. MATERIALS AND METHODS: A computerized literature search was carried out in PubMed, the Chinese Biomedicine (CBM) database, China National Knowledge Infrastructure (CNKI) platform, and the Wanfang database (Chinese) to collect relevant articles. RESULTS: A total of 11 articles including 1,738 ALL cases and 2,438 controls were included in this meta-analysis. Overall, a significantly decreased association was found between the MTHFR C677T polymorphism and ALL risk when all studies in Chinese populations were pooled into the meta-analysis. In subgroup analyses stratified by age, ethnicity, and source of controls, the same results were observed in children, in population-based studies, and in people with no stated ethnicity. However, a significantly increased association was also found for MTHFR C677T in hospital-based studies, and for MTHFR A1298C in people with no stated ethnicity. CONCLUSION: Our results suggest that the MTHFR C677T and A1298C polymorphisms may be potential biomarkers for ALL risk in Chinese populations, and studies with a larger sample size and wider population spectrum are required before definitive conclusions can be drawn.