Radiomics signature: A potential biomarker for the prediction of MGMT promoter methylation in glioblastoma.

BACKGROUND: In glioblastoma (GBM), promoter methylation of the DNA repair gene O-methylguanine-DNA methyltransferase (MGMT) is associated with beneficial chemotherapy. PURPOSE/HYPOTHESIS: To analyze radiomics features for utilizing the full potential of medical imaging as biomarkers of MGMT promoter methylation. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: In all, 98 GBM patients with known MGMT (48 methylated and 50 unmethylated tumors). FIELD STRENGTH/SEQUENCE: 3.0T magnetic resonance (MR) images, containing T1 -weighted image (T1 WI), T2 -weighted image (T2 WI), and enhanced T1 WI. ASSESSMENT: A region of interest (ROI) of the tumor was delineated. A total of 1665 radiomics features were extracted and quantized, and were reduced using least absolute shrinkage and selection operator (LASSO) regularization. STATISTICAL TESTING: After the support vector machine construction, accuracy, sensitivity, and specificity were computed for different sequences. An independent validation cohort containing 20 GBM patients was utilized to further evaluate the radiomics model performance. RESULTS: Radiomics features of T1 WI reached an accuracy of 67.54%. Enhanced T1 WI features reached an accuracy of 82.01%, while T2 WI reached an accuracy of 69.25%. The best classification system for predicting MGMT promoter methylation status originated from the combination of 36 T1 WI, T2 WI, and enhanced T1 WI images features, with an accuracy of 86.59%. Further validation on the independent cohort of 20 patients produced similar results, with an accuracy of 80%. DATA CONCLUSION: Our results provide further evidence that radiomics MR features could predict MGMT methylation status in preoperative GBM. Multiple imaging modalities together can yield putative noninvasive biomarkers for the identification of MGMT. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1380-1387.

Predicting Disease-Free Survival With Multiparametric MRI-Derived Radiomic Signature in Cervical Cancer Patients Underwent CCRT.

Prognostic biomarkers that can reliably predict the disease-free survival (DFS) of locally advanced cervical cancer (LACC) are needed for identifying those patients at high risk for progression, who may benefit from a more aggressive treatment. In the present study, we aimed to construct a multiparametric MRI-derived radiomic signature for predicting DFS of LACC patients who underwent concurrent chemoradiotherapy (CCRT). METHODS: This multicenter retrospective study recruited 263 patients with International Federation of Gynecology and Obetrics (FIGO) stage IB-IVA treated with CCRT for whom pretreatment MRI scans were performed. They were randomly divided into two groups: primary cohort (n = 178) and validation cohort (n = 85). The LASSO regression and Cox proportional hazard regression were conducted to construct the radiomic signature (RS). According to the cutoff of the RS value, patients were dichotomized into low- and high-risk groups. Pearson's correlation and Kaplan-Meier analysis were conducted to evaluate the association between the RS and DFS. The RS, the clinical model incorporating FIGO stage and lymph node metastasis by the multivariate Cox proportional hazard model, and a combined model incorporating RS and clinical model were constructed to estimate DFS individually. RESULTS: The final radiomic signature consisted of four radiomic features: T2W_wavelet-LH_ glszm_Size Zone NonUniformity, ADC_wavelet-HL-first order_ Median, ADC_wavelet-HH-glrlm_Long Run Low Gray Level Emphasis, and ADC_wavelet _LL_gldm_Large Dependence High Gray Emphasis. Higher RS was significantly associated with worse DFS in the primary and validation cohorts (both p<0.001). The RS demonstrated better prognostic performance in predicting DFS than the clinical model in both cohorts (C-index, 0.736-0.758 for RS, and 0.603-0.649 for clinical model). However, the combined model showed no significant improvement (C-index, 0.648, 95% CI, 0.571-0.685). CONCLUSIONS: The present study indicated that the multiparametric MRI-derived radiomic signature could be used as a non-invasive prognostic tool for predicting DFS in LACC patients.

Predicting response to electroconvulsive therapy combined with antipsychotics in schizophrenia using multi-parametric magnetic resonance imaging.

Electroconvulsive therapy (ECT) has been shown to be effective in schizophrenia, particularly when rapid symptom reduction is needed or in cases of resistance to drug treatment. However, there are no markers available to predict response to ECT. Here, we examine whether multi-parametric magnetic resonance imaging (MRI)-based radiomic features can predict response to ECT for individual patients. A total of 57 treatment-resistant schizophrenia patients, or schizophrenia patients with an acute episode or suicide attempts were randomly divided into primary (42 patients) and test (15 patients) cohorts. We collected T1-weighted structural MRI and diffusion MRI for 57 patients before receiving ECT and extracted 600 radiomic features for feature selection and prediction. To predict a continuous improvement in symptoms (ΔPANSS), the prediction process was performed with a support vector regression model based on a leave-one-out cross-validation framework in primary cohort and was tested in test cohort. The multi-parametric MRI-based radiomic model, including four structural MRI feature from left inferior frontal gyrus, right insula, left middle temporal gyrus and right superior temporal gyrus respectively and six diffusion MRI features from tracts connecting frontal or temporal gyrus possessed a low root mean square error of 15.183 in primary cohort and 14.980 in test cohort. The Pearson's correlation coefficients between predicted and actual values were 0.671 and 0.777 respectively. These results demonstrate that multi-parametric MRI-based radiomic features may predict response to ECT for individual patients. Such features could serve as prognostic neuroimaging biomarkers that provide a critical step toward individualized treatment response prediction in schizophrenia.

Baseline Brain Gray Matter Volume as a Predictor of Acupuncture Outcome in Treating Migraine.

Background: The present study aimed to investigate the use of imaging biomarkers to predict the outcome of acupuncture in patients with migraine without aura (MwoA). Methods: Forty-one patients with MwoA received 4 weeks of acupuncture treatment and two brain imaging sessions at the Beijing Traditional Chinese Medicine Hospital affiliated with Capital Medical University. Patients kept a headache diary for 4 weeks before treatment and during acupuncture treatment. Responders were defined as those with at least a 50% reduction in the number of migraine days. The machine learning method was used to distinguish responders from non-responders based on pre-treatment brain gray matter (GM) volume. Longitudinal changes in GM predictive regions were also analyzed. Results: After 4 weeks of acupuncture, 19 patients were classified as responders. Based on 10-fold cross-validation for the selection of GM features, the linear support vector machine produced a classification model with 73% sensitivity, 85% specificity, and 83% accuracy. The area under the receiver operating characteristic curve was 0.7871. This classification model included 10 GM areas that were mainly distributed in the frontal, temporal, parietal, precuneus, and cuneus gyri. The reduction in the number of migraine days was correlated with baseline GM volume in the cuneus, parietal, and frontal gyri in all patients. Moreover, the left cuneus showed a longitudinal increase in GM volume in responders. Conclusion: The results suggest that pre-treatment brain structure could be a novel predictor of the outcome of acupuncture in the treatment of MwoA. Imaging features could be a useful tool for the prediction of acupuncture efficacy, which would enable the development of a personalized medicine strategy.

Association Between Connectivity of Hippocampal Sub-Regions and Auditory Verbal Hallucinations in Schizophrenia.

Background: Hippocampal dysconnectivity has been detected in schizophrenia patients with auditory verbal hallucinations (AVHs). Neuroanatomical evidence has indicated distinct sub-regions in the hippocampus, but which sub-regions within the hippocampus may emerge dysfunction in the brain network, and the relationship between connection strength and the severity of this debilitating disorder have yet to be revealed. Masked independent component analysis (mICA), i.e., ICA restricted to a defined region of interest, can provide insight into observing local functional connectivity in a particular brain region. We aim to map out the sub-regions in the hippocampus with dysconnectivity linked to AVHs in schizophrenia. Methods: In this functional magnetic resonance imaging study of schizophrenia patients with (n = 57) and without (n = 83) AVHs, and 71 healthy controls, we first examined hippocampal connectivity using mICA, and then the correlation between connection metric and clinical severity was generated. Results: As compared with patients without AVHs, mICA showed a group of hyper-connections for the left middle part, as well as another group of hypo-connections for the bilateral antero-lateral and right antero-medial parts in patients with AVHs. Connectivity was linked to the clinical symptoms scores in the sample of patients with AVHs. Conclusion: These findings demonstrate that the left middle part is more densely connected, but the bilateral antero-lateral and right antero-medial parts are more sparsely connected in schizophrenia patients with AVHs. The findings in the present study show proof of precious location in the hippocampus mediating the neural mechanism behind AVHs in schizophrenia.

[Investigation on nutritional intakes for hospitalized children with blood disease].

OBJECTIVE: To investigate the diet and nutritional status of hospitalized children with blood disease in order to provide nutritional guidelines. METHODS: The patients' daily dietary intakes, including breakfast, lunch, dinner and additional meals, were recorded in detail for seven consecutive days. The intake amount of various nutrients was calculated using the dietary database. RESULTS: The majority of children with blood disease showed inadequate intakes of calories [mean 1825.81 kCal/d, 73.62% of the recommended intake (RNI)] and protein (mean 67.68 g/d, 81.34% of RNI). Intakes of vitamin E and riboflavin were adequate, but intakes of vitamin A, thiamine and vitamin C (66.67%, 77.78% and 69.89% of RNI, respectively) were inadequate. Iron and selenium intakes were adequate, but calcium and zinc intakes (41.11% and 56.21% of RNI, respectively) were grossly inadequate. CONCLUSIONS: Hospitalized children with blood disease had decreased dietary intakes of calories, protein, vitamin A, vitamin C, thiamin, calcium and zinc. The dietary pattern and nutritional intake need to be improved.

Hemangiopoietin supports animal survival and accelerates hematopoietic recovery of chemotherapy-suppressed mice.

OBJECTIVE: To determine if recombinant human hemangiopoietin (HAPO), a novel growth factor for primitive cells of hematopoietic and endothelial cell lineages, accelerates hematopoietic reconstitution after high-dose chemotherapy in vivo in mice. METHODS: Male Balb/c mice after treatment of 5-fluorouracil were subcutaneously injected with HAPO or its dilution for consecutive 10 d. Their survival and body weight together with peripheral blood were routinely tested. At day 7 and 14, the numbers of bone marrow (BM) cells as well as colony-forming units (CFU) after in vitro colony culture were counted. The peripheral blood CFU and the percentage of CD34+ CD117+ cells in BM were analyzed. Transwell chamber was used for cell migratory assay. RESULTS: HAPO at different doses significantly increased the survival rate and body weight, with an optimal effect in the HAPO 10 microg/d group. The number of BM cells and the percentage of CD34+ CD117+ cells were also increased after HAPO administration. The number of granulocyte/macrophage CFU and granulocyte, erythroid, macrophage and megakaryocyte CFU in BM after HAPO treatment was greater than that from the HAPO dilution group. More circulating CFU could be observed after injection of HAPO. In addition, this novel cytokine had a chemotactic effect on the hematopoietic stem/progenitor cells. CONCLUSION: HAPO improves animal survival and accelerates hematopoietic reconstitution of mice after high-dose chemotherapy.

Cerebral blood flow and its connectivity features of auditory verbal hallucinations in schizophrenia: A perfusion study.

The goal of the study was to investigate cerebral blood flow (CBF) and its connectivity (an across-subject covariance measure) patterns of schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs). A total of demographically matched 25 SZ patients with AVHs, 25 without AVHs, and 25 healthy controls (HCs) underwent resting state perfusion imaging using a pulsed arterial spin labeling sequence. CBF and its connectivity were analyzed and then CBF topological properties were calculated. AVHs patients exhibited decreased CBF in the bilateral superior and middle frontal gyri and postcentral gyri, and right supplementary motor area compared with SZ patients without AVHs. SZ patients without AVHs showed reduced CBF in the left middle frontal gyrus relative to HCs. Moreover, AVHs groups showed distinct connectivity pattern, an intermediate level between HCs and patients without AVHs in the global efficiency. Our study demonstrates aberrant CBF in the brain regions associated with inner speech monitoring and language processing in SZ patients with AVHs. The complex network measures showed by CBF-derived functional connectivity indicate dysconnectivity between different functional units within the network of AVHs in SZ. Our findings might shed light on the neural underpinnings behind AVHs in this devastating disease at the level of CBF and its connectivity.

Aberrant perfusion and its connectivity within default mode network of first-episode drug-naïve schizophrenia patients and their unaffected first-degree relatives.

Neural substrates behind schizophrenia (SZ) and its heritability mediated by brain function are largely unknown. Cerebral blood flow (CBF), as a biomarker of activation in the brain, reflects the neuronal metabolism, and is promisingly used to detect cerebral alteration thereby shedding light on the features of individuals at high genetic risk. We performed a cross-sectional functional magnetic resonance imaging (MRI) study enrolling 45 first-episode drug-naïve patients with SZ, 32 unaffected first-degree relatives of these patients, and 51 healthy controls (HCs). We examined CBF, CBF connectivity, and CBF topological properties. SZ patients showed increased CBF in the left medial superior frontal gyrus and right precuneus compared with HCs, and decreased CBF in the left middle temporal gyrus compared with their relatives. Furthermore, unaffected relatives revealed higher level of CBF pronounced in regions within default mode network (DMN). Both SZ patients and their relatives exhibited dysconnectivity patterns. Notably, as for the network properties, unaffected relatives were with an intermediate level between SZ patients and HCs in the local efficiency and global efficiency. Our findings demonstrate the aberrant CBF of areas within DMN and the CBF connectivity pattern might be a familial feature in the brain of first-episode SZ patients and their relatives.

[Effect of flavonoids from Hippophae rhamniodes residues on blood lipoid metabolism and antioxidative activity in climacteric rats].

OBJECTIVE: To study the effect of flavonoids from seed residues of Hippophae rhamnoides (FH) on the lipid metabolism and antioxidative activity in climacteric rats. METHOD: Menopausal rats with aging were used in this experiment. The rats were fed with FH by gastrogavage for 13 weeks. The effect of drug on the lipid metabolism and the antioxidative activity were observed after the rats were killed. RESULT: Serum total cholesterol was decreased significantly in rats fed with FH, T-AOC and SOD in serum and liver were significantly higher than those in rats fed with water, and at the same time MDA was lower than that in rats fed with water. CONCLUSION: FH can improve the climacteric rats' lipid metabolism, and enhance the antioxidation in climacteric rats.