Gaining Insight into Updated MR Imaging for Quantitative Assessment of Cartilage Injury in Knee Osteoarthritis.

PURPOSE OF THE REVIEW: Knee Osteoarthritis (KOA) entails progressive cartilage degradation, reviewed via MRI for morphology, biochemical composition, and microtissue alterations, discussing clinical advantages, limitations, and research applicability. RECENT FINDINGS: Compositional MRI, like T2/T2* mapping, T1rho mapping, gagCEST, dGEMRIC, sodium imaging, diffusion-weighted imaging, and diffusion-tensor imaging, provide insights into cartilage injury in KOA. These methods quantitatively measure collagen, glycosaminoglycans, and water content, revealing important information about biochemical compositional and microstructural alterations. Innovative techniques like hybrid multi-dimensional MRI and diffusion-relaxation correlation spectrum imaging show potential in depicting initial cartilage changes at a sub-voxel level. Integration of automated image analysis tools addressed limitations in manual cartilage segmentation, ensuring robust and reproducible assessments of KOA cartilage. Compositional MRI techniques reveal microstructural changes in cartilage. Multi-dimensional MR imaging assesses biochemical alterations in KOA-afflicted cartilage, aiding early degeneration identification. Integrating artificial intelligence enhances cartilage analysis, optimal diagnostic accuracy for early KOA detection and monitoring.

Do Habitat MRI and Fractal Analysis Help Distinguish Triple-Negative Breast Cancer From Non-Triple-Negative Breast Carcinoma.

Purpose: To determine whether multiparametric MRI-based spatial habitats and fractal analysis can help distinguish triple-negative breast cancer (TNBC) from non-TNBC. Method: Multiparametric DWI and DCE-MRI at 3T were obtained from 142 biopsy- and surgery-proven breast cancer with 148 breast lesions (TNBC = 26 and non-TNBC = 122). The contrast-enhancing lesions were divided into 3 spatial habitats based on perfusion and diffusion patterns using K-means clustering. The fractal dimension (FD) of the tumour subregions was calculated. The accuracy of the habitat segmentation was measured using the Dice index. Inter- and intra-reader reliability were evaluated with the intraclass correlation coefficient (ICC). The ability to predict TNBC status was assessed using the receiver operating characteristic curve. Results: The Dice index for the whole tumour was 0.81 for inter-reader and 0.88 for intra-reader reliability. The inter- and intra-reader reliability were excellent for all 3 tumour habitats and fractal features (ICC > 0.9). TNBC had a lower hypervascular cellular habitat and higher FD 1 compared to non-TNBC (all P < .001). Multivariate analysis confirmed that hypervascular cellular habitat (OR = 0.88) and FD 1 (OR = 1.35) were independently associated with TNBC (all P < .001) after adjusting for rim enhancement, axillary lymph nodes status, and histological grade. The diagnostic model combining hypervascular cellular habitat and FD 1 showed excellent discriminatory ability for TNBC, with an AUC of 0.951 and an accuracy of 91.9%. Conclusions: The fraction of hypervascular cellular habitat and its FD may serve as useful imaging biomarkers for predicting TNBC status.

Dynorphin participates in interaction between depression and non-erosive reflux disease.

BACKGROUND: To explore the relationships between anxiety/depression and NERD, we focused on dynorphin (Dyn), an important member of visceral hypersensitivity, and its related pathways. METHODS: Pearson's correlation analysis on patients with NERD and in vivo experiment on NERD rat model. Part 1: Pearson's correlation analysis among serum levels of Dyn, clinical symptoms and HADS scores of NERD patients were carried on. Part 2: Wistar rats were randomly divided into 2 groups: control group and model group. The data of pH value, immobility time, serum Dyn concentration, NMDAR1 and SP expression were, respectively, derived from automatic pH recorder, tail suspension test, enzyme-linked immunosorbent assay, immunohistochemistry and immunofluorescence. RESULTS: Part 1: Pearson's correlation analysis showed that there was a linear correlation between Clinical Symptom (CS) score and HADS score (HAD-A, HAD-D), and the correlation coefficients were 0.385 and 0.273 respectively; the correlation coefficient between lg (Dyn) and lg (CS score) was r = 0.441, P = 0.002; the correlation coefficient between lg(Dyn) and lg (HAD-D score) was r = 0.447, P = 0.002. Part 2: The pH value of the lower esophagus in the model group was lower than that in the control group (P < 0.01). The tail suspension immobility time of model group was significantly longer than that of control group (P < 0.01). The serum Dyn concentration and the expression level of NMDAR1 in spinal cord and SP in lower esophageal mucosa of model group were significantly higher than those of control group (P < 0.05). CONCLUSION: Increased serum dynorphin level may be a sign of correlation between depression and NERD.

Association of Serum Ferritin With Marrow Iron Concentration Using a Three-Dimension Fat Analysis & Calculation Technique Sequence in Postmenopausal Women.

OBJECTIVE: The aim of the study was to determine whether serum iron and ferritin levels are determinants of iron accumulation in bone marrow using a three-dimension Fat Analysis & Calculation Technique (FACT) sequence. METHODS: We measured spinal marrow R2* using a 3T FACT sequence in 112 postmenopausal women (mean age, 62.6 years; range, 50-82.6 years). Serum iron and ferritin levels were determined in blood specimens. Lumbar spine bone mineral density was measured by dual-energy x-ray absorptiometry. The levels of serum iron and ferritin were evaluated in relation to the spinal marrow R2* values before and after adjustments for potential confounders. RESULTS: In the unadjusted model, magnetic resonance imaging-based spinal marrow R2* was positively correlated to the levels of serum ferritin (Spearman ρ = 0.436, P < 0.001) and iron (Spearman ρ = 0.245, P = 0.009). Multiple stepwise linear regression analyses (adjusting for age, years since menopause, body mass index, alcohol intake, tobacco use, physical activity, serum lipids profile, biomarkers of bone turnover, and lumbar spine bone density) were performed in 3 separate models with marrow R2* values as potential explanatory variables. The level of serum ferritin, but not iron, was an independent predictor of marrow R2* (standardized ß coefficient, 0.302, 95% confidence interval, 0.141-0.509, P = 0.001). Similarly, spinal marrow R2* increased with a linear trend from the lowest (<139 ng/mL) to highest (≥180 ng/mL) serum ferritin quartiles (P for trend = 0.007). CONCLUSIONS: Quantitative assessment of R2* derived from FACT is a fast, simple, noninvasive, and nonionizing method to evaluate marrow iron accumulation.

Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer.

Zinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-ß, ß-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.

Recombinant Human Growth Hormone Ameliorates Cognitive Impairment in Stroke Patients.

OBJECTIVE: We aimed to determine the effects of recombinant human growth hormone (rhGH) replacement on cognitive function in subjects with poststroke cognitive impairment using resting-state functional magnetic resonance imaging. METHODS: We included 60 patients with a first-ever stroke for 3 months and a diagnosis of cognitive impairment who were randomized 1:1 to receive either rhGH subcutaneously or placebo injection for 6 months. All subjects were required to receive the same rehabilitative therapy program. Both groups were subjected to pretreatment and posttreatment neuropsychological assessment using the Montreal Cognitive Assessment, serum neurotrophic factors, biomarkers of glucose and lipid metabolism, and functional magnetic resonance imaging during 6 months of the study period. The pattern of brain activity was determined by examining the functional connectivity and amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. RESULTS: Forty-three (82.7%) completed the study. Treatment with rhGH reduced levels of triglycerides and low-density lipoprotein cholesterol but did not significantly altered plasma concentrations of glucose and glycated hemoglobin. We found a significant increase in serum insulin-like growth factor 1 levels (32.6%; P < 0.001) in the rhGH-treated group compared with that in the controls. After 6 months of rhGH treatment, mean Montreal Cognitive Assessment score improved from 16.31 (5.32) to 21.19 (6.54) (P < 0.001). The rhGH group showed significant increased area of activation with increased ALFF values in the regions of the frontal lobe, putamen, temporal lobe, and thalamus (P < 0.05), relative to the baseline conditions. The correlation analysis revealed that the ALFF and functional connectivity of default mode network was positively correlated with the ΔMoCA score and ΔIGF-1 levels; that is, the more the scale score increased, the higher the functional connection strength. No undesirable adverse effects were observed. CONCLUSIONS: The rhGH replacement has a significant impact on global and domain cognitive functions in poststroke cognitive impairment.

Resveratrol induces autophagy-dependent apoptosis in HL-60 cells.

BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student's unpaired t test. RESULTS: We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. CONCLUSIONS: These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways.

DNA methylation of a non-CpG island promoter represses NQO1 expression in rat arsenic-transformed lung epithelial cells.

NAD(P)H:quinone oxidoreductase 1 (NQO1), a phase II flavoenzyme that catalyzes reduction reactions to protect cells against electrophiles and oxidants, is involved in tumorigenesis. Altered methylation of the NQO1 gene has been observed and is speculated to result in aberrant NQO1 expression in rat cells undergoing chemical carcinogenesis, although this has not been proven experimentally. In this study, we first investigated the potential epigenetic mechanisms underlying the phenomenon of NQO1 differential expression in individual subclones of rat arsenic-transformed lung epithelial cells (TLECs). NQO1 expression of TLEC subclones with or without 5-aza-2'-deoxycytidine (5-Aza-CdR) treatment was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot analysis, and real-time PCR. Methylation status of the NQO1 promoter in TLEC subclones was analyzed by bisulfite sequencing. Transcriptional activity of NQO1 promoter in vitro methylated was determined by luciferase assay using a CpG-free luciferase reporter driven by the NQO1 promoter region (-435 to +229). We found that non-CpG island (non-CpGI) within the NQO1 promoter was hyper- or hypo-methylated in TLEC subclones and corresponded to low and high gene expressions, respectively. Following the treatment with 5-Aza-CdR, transcription of the NQO1 gene in the hypermethylated subclones was restored, accompanied by demethylation of the NQO1 promoter. In vitro promoter methylation almost completely silenced reporter activity in TLECs. These results indicate that DNA methylation of the non-CpGI promoter contributes to epigenetic silencing of NQO1 in rat TLECs.

Comparison of chemical shift-encoded water-fat MRI and MR spectroscopy in quantification of marrow fat in postmenopausal females.

PURPOSE: To validate a chemical shift-encoded (CSE) water-fat imaging for quantifying marrow fat fraction (FF), using proton magnetic resonance spectroscopy (MRS) as reference. MATERIALS AND METHODS: Multiecho T2 -corrected MRS and CSE imaging with eight-echo gradient-echo acquisitions at 3T were performed to calculate marrow FF in 83 subjects, including 41 with normal bone mineral density (BMD), 26 with osteopenia, and 16 with osteoporosis (based on DXA). Eight participants were scanned three times with repositioning to assess the repeatability of CSE FF map measurements. Pearson correlation coefficient, Bland-Altman 95% limit of agreement, and Lin's concordance correlation coefficient were calculated. RESULTS: The Pearson correlation coefficient was 0.979 and Lin's concordance correlation coefficient was 0.962 between CSE-based FF and MRS-based FF. All data points, calculated using the Bland-Altman method, were within the limits of agreement. The intra- and interrater agreement for average CSE-based FF was excellent (intrarater, intraclass correlation coefficient [ICC] = 0.993; interrater, ICC = 0.976-0.982 for different BMD groups). In the subgroups of varying BMD, inverse correlations were observed to be very similar between BMD (r = -0.560 to -0.710), T-score (r = -0.526 to -0.747), and CSE-based FF, and between BMD (r = -0.539 to -0.706), T-score (r = -0.501 to -0.742), and MRS-based FF even controlling for age, years since menopause, and body mass index. The repeatability for CSE FF map measurements expressed as absolute precision error was 1.45%. CONCLUSION: CSE imaging is equally accurate in characterizing marrow fat content as MRS. Given its excellent correlation and concordance with MRS, the CSE sequence could be used as a potential replacement technique for marrow fat quantification. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:66-73.

Differential effects of bisphenol A diglicydyl ether on bone quality and marrow adiposity in ovary-intact and ovariectomized rats.

Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promote bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups for 12 wk (n = 10/group): sham+vehicle, sham+BADGE, OVX+vehicle, and OVX+BADGE. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR, and Western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, and adipogenic markers PPARγ2 and C/EBPα by ∼50% in OVX rats. Similar results were observed in sham rats vs. vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength, and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30 mg/kg attenuates marrow adiposity in ovary-intact and OVX rats and stimulates bone formation in ovary-intact rats but does not significantly rescue bone quality in OVX rats.

To assess the association between vertebral marrow fat content and colorectal adenoma in postmenopausal women using magnetic resonance spectroscopy.

BACKGROUND: Although lower bone mineral density (BMD) is considered to have an increased risk for colorectal adenoma, no association between marrow fat content and colorectal adenoma has been elucidated yet. PURPOSE: To evaluate the relationship between marrow fat fraction (MFF) and the presence of colorectal adenoma in postmenopausal women using magnetic resonance spectroscopy (MRS). MATERIAL AND METHODS: We performed a cross-sectional observational study on 152 postmenopausal patients with colorectal adenoma and 100 matched control subjects who underwent screening colonoscopy, biochemical measurements, dual-energy X-ray absorptiometry, and MRS. Logistic regression models were performed to assess the relationships among BMD, MFF, and colorectal adenoma. RESULTS: With univariate analysis, marrow fat accumulation was higher and BMD values were lower in patients with colorectal adenoma compared with those in controls. After adjustment for potential confounders including demographics, health history, blood lipid levels, indexes of glucose metabolism, and validated measures of diet and physical activity, MFF was significantly positively associated with colorectal adenoma (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.10-2.46; P = 0.008). Vertebral BMD, but not total hip and femoral neck BMD, was inversely related with colorectal adenoma (OR, 0.62; 95% CI, 0.14-0.89; P = 0.027). Additionally, MFF was associated with adenoma number, size, and high-risk adenoma (all P < 0.01). MFF was found to be an independent risk factor of a high-risk colorectal adenoma (OR, 2.08; 95% CI, 1.24-3.60; P = 0.019). CONCLUSION: Marrow fat accumulation is highly associated with colorectal adenoma, particularly high-risk adenoma, in postmenopausal women.

Short- and midterm reproducibility of marrow fat measurements using mDixon imaging in healthy postmenopausal women.

OBJECTIVE: We tested the short- and midterm reproducibility of vertebral marrow fat fraction (FF) measurements using mDixon imaging. MATERIALS AND METHODS: Thirty postmenopausal women underwent mDixon scans to obtain L1-4 FF from three slices per vertebra by two independent observers (session 1). Measurements were repeated after 6 weeks (session 2) and 6 months (session 3). The mean FF for three regions of interest per vertebra was calculated. The coefficients of variation (CVs) were calculated for each participant and imaging session, and the intraclass correlation coefficients (ICCs) were calculated to assess interobserver and intersession agreements. RESULTS: There were no significant differences in FF measurements among the three slices, imaging sessions or observers. The mean intrasubject CV for FF measurement reproducibility was 1.94 %. The interobserver agreement for the average FF value was excellent (ICC ≥0.945 for each session). The ICC for intersession agreement was excellent (ICC ≥0.955 between sessions). The mean intersession CV was lower within a short-term interval (2.97 %) than within sessions 1 and 3 (4.80 %) or sessions 3 and 2 (4.44 %). The overall mean CV for the reproducibility of FF measured with mDixon imaging over the short- and midterm was 4.09 % (95 % CI, 3.79-4.40 %). CONCLUSION: mDixon is a reproducible method for FF quantification over short- and midterm intervals up to 6 months in healthy postmenopausal women. Our results also provide data by which a power analysis can be optimized when designing studies involving the use of FF derived from similar mDixon sequences.

An Electrolyte Engineered Homonuclear Copper Complex as Homogeneous Catalyst for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries suffer from severe polysulfide shuttle, retarded sulfur conversion kinetics and notorious lithium dendrites, which has curtailed the discharge capacity, cycling lifespan and safety. Engineered catalysts act as a feasible strategy to synchronously manipulate the evolution behaviors of sulfur and lithium species. Herein, a chlorine bridge-enabled binuclear copper complex (Cu-2-T) is in situ synthesized in electrolyte as homogeneous catalyst for rationalizing the Li-S redox reactions. The well-designed Cu-2-T provides completely active sites and sufficient contact for homogeneously guiding the Li2S nucleation/decomposition reactions, and stabilizing the lithium working interface according to the synchrotron radiation X-ray 3D nano-computed tomography, small angle neutron scattering and COMSOL results. Moreover, Cu-2-T with the content of 0.25 wt% approaching saturated concentration in electrolyte further boosts the homogeneous optimization function in really operated Li-S batteries. Accordingly, the capacity retention of the Li-S battery is elevated from 51.4% to 86.3% at 0.2 C, and reaches 77.0% at 1.0 C over 400 cycles. Furthermore, the sulfur cathode with the assistance of Cu-2-T realizes the stable cycling under the practical scenarios of soft-packaged pouch cell and high sulfur loading (6.5 mg cm-2 with the electrolyte usage of 4.5 µL mgS -1).

Chlorine bridge bond-enabled binuclear copper complex for electrocatalyzing lithium-sulfur reactions.

Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium-sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium-sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium-sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm-2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm-2 and electrolyte dosage of 4.8 µL mg-1.

Prediction of hip osteoporotic fractures from composite indices of femoral neck strength.

OBJECTIVE: To clarify whether composite hip strength indices improve predictive ability for hip osteoporotic fractures independent of conventional bone mineral density (BMD). SUBJECTS AND METHODS: Three hundred and eighty-two health controls and 43 women with hip fractures (aged 28.2-87.7 years, mean age 59.5 ± 9.2 years) were measured by dual energy X-ray absorptiometry for femoral neck bone mineral density (FN_BMD) and proximal femur geometry parameters of hip, and composite hip strength indices (Compression strength index, Bending strength index, and Impact strength index). The association between the studied parameters and the fractures was modelled using multiple logistic regression, including age, height, weight, and menopausal status. Fracture-predicted probability was calculated for each predictor tested. ROC curve areas (AUCs) were calculated for the fracture status, having the calculated fracture-predicted probability as a test variable. AUCs were compared by the Hanley-McNeil test. RESULTS: Women with hip fractures had lower FN_BMD, composite hip strength indices, and longer hip axis length than controls, and no significant difference in femoral neck width. Logistic regression showed composite hip strength indices could predict hip fractures risk. To the same extent as FN BMD, Compression Strength Index (CSI) best predicted the risk for each fracture (AUC = 0.787 ± 0.028). When CSI was added to FN_BMD, there was a small but not statistically significant increase in AUC to 0.796 ± 0.027 (P = 0.9018). CONCLUSION: Composite indices of femoral neck strength may be valuable in the assessment of the biomechanics of bone fragility; however, they do not appear to add diagnostic value to the simple measurement of BMD.

The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis.

OBJECTIVE: To characterize the temporal changes in marrow lipids content and adipocytes in the development of glucocorticoid-induced osteoporosis (GIOP) in rabbits using MR spectroscopy. SUBJECTS AND METHODS: Twenty 20-week-old female rabbits were randomized to a control group and a GIOP group equally. Marrow lipids fraction and bone mineral density at the left proximal femur and L3-L4 vertebrae were measured by MR spectroscopy and dual-energy X-ray absorptiometry at week 0, 4, 8, and 12. Marrow adipocytes were quantitatively evaluated by histopathology. RESULTS: Marrow adiposity in the GIOP group showed a significant increase over time, with a variation of marrow lipids fraction (+35.9 %) at week 4 from baseline and it was maintained until week 12 (+75.2 %, p < 0.001 for all). The GIOP group demonstrated continuous deterioration of bone with significant difference between the two groups at week 8, followed by increased marrow fat with significant difference at week 4 (p < 0.05 for all). In comparison with the controls, marrow adipocyte density in the GIOP group increased by 57.1 % at week 8 and 35.4 % at week 12, respectively. A reduction (-13.3 %) in adipocyte mean diameter at week 8 (but an increase (+22.7 %) at week 12) were observed in the GIOP group compared with the control group (p < 0.05 for all). There was significant difference between two periods (p = 0.023) in adipocyte mean diameter in the GIOP group. The percentage area of marrow adipocytes in the GIOP group was 62.8 ± 8.7 % at week 8 and 79.2 ± 7.7 % at week 12, both of which were significantly higher than those of the controls (p < 0.05 for all). CONCLUSIONS: Marrow adipogenesis is synchronized with bone loss in the development of GIOP, which was characterized by a significant increase in the number of small-sized marrow adipocytes in the relatively early stage and concomitant volume increase later on. MR spectroscopy appears to be the most powerful tool for detecting the sequential changes in marrow lipid content.

Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI.

BACKGROUND: The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI. METHODS: Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS. RESULTS: Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS. CONCLUSION: dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.

Comparative proteomic analysis of differentiation of mouse F9 embryonic carcinoma cells induced by retinoic acid.

The multipotent mouse F9 embryonic carcinoma cell is an ideal model system to investigate the mechanism of retinoic acid (RA) in cell differentiation and cell growth control and the biochemical basis of early embryonic development. We reported here a proteomics approach to study protein expression changes during the differentiation of F9 cells into the visceral endoderm. F9 cells were incubated with or without RA at 0, 24, 48, and 72 h. Total proteins extracted were separated by two-dimensional electrophoresis (2-DE) and the protein patterns on the gels were comparatively analyzed by computer. Approximately 1,100 protein spots were detected in the F9 proteome, within the pH 3-10 range. Fourteen protein spots which the levels of expression were found to be altered dramatically during the F9 cells differentiating, and were identified by MALDI-TOF MS or ESI-MS/MS. These proteins included metabolism enzymes, HSP60s, RAN, hnRNP K, FUBP1, VDAC1, STI1, and prohibitin. These proteins are involved in cellar metabolism, gene expression regulation, stress response, and apoptosis, respectively. The data from proteomic analyze are consistent with the result obtained from Western blot analysis. This study increases our understanding of the proteomics changes during F9 cells differentiation induced by RA.

MR spectroscopy and micro-CT in evaluation of osteoporosis model in rabbits: comparison with histopathology.

PURPOSE: To explore the evidence of regular alteration of bone quality in osteoporosis dynamically examined by MRS and micro-CT, comparing with histopathology. METHODS: Forty rabbits were allocated into two groups. Group A were used as sham. Group B underwent bilateral ovariectomy (OVX) combined with daily intramuscular methylprednisolone, underwent MR spectroscopy, micro-CT, and histopathology of L5 at 2, 4, 8, and 10 weeks after operation. RESULTS: Fat fraction as shown by MRS in Group B was significantly increased over the time course of osteoporosis development with significant difference between two groups at 4, 8, and 10 weeks after OVX. Continuous deterioration of cancellous bone architecture in Group B, was first detected at week 4. FF value in group B correlated with micro-CT parameters. Marrow fat as measured by MR and CT was positively correlated with both the mean density and diameter of adipocytes (both of which increased over time). CONCLUSIONS: Marrow adipogenesis occurs in synchrony with deterioration of trabecular microarchitecture.MRS may be valuable to assess the pathophysiological changes of bone marrow in osteoporosis in early stage. KEY POINTS: MRS revealed gradually increasing bone marrow fat in rabbits rendered osteoporotic. Marrow adipogenesis occurs in synchrony with deterioration of trabecular microarchitecture. Pathology revealed an early increase in number of marrow adipocytes in osteoporosis. MRS may help assess early pathophysiological bone marrow changes in osteoporosis.

Effects of Total Flavonoids of Epimedium on Bone Marrow Adipose Tissue in Ovariectomized Rats.

Bone marrow adipose tissue has brown fat characteristics. Several studies have demonstrated that total flavonoids of Epimedium (TFE) could prevent bone loss and reduce the white adiposity in bone marrow induced by ovariectomy (OVX) in rats. However, the effects of TFE on marrow brown fat in OVX rats remain unclear. In this word, we addressed this question expected to provide a new target for preventing and treating osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were equally divided into Sham controls, OVX controls, and OVX treated with TFE. Chemical shift coding magnetic resonance was performed to detect marrow fat fraction at the left femur at baseline, 6 and 12 weeks post-OVX. Bone mineral density at the lumbar spine and femur was measured by dual-energy x-ray absorptiometry. Serum bone biomarkers by ELISA, trabecular bone microarchitecture at the proximal tibia by micro-CT, quantitative parameters of marrow adipocyte by hematoxylin, and eosin staining were evaluated. The marrow adipocyte gene and protein expressions profile were determined by real-time quantitative PCR and immunostaining in whole tibiae. We found that TFE treatment could decrease bone turnover rate and improved bone mineral density and trabecular microarchitecture in OVX rats. OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARγ2 and FABP4. These pathological changes induced by estrogen deficiency were restored by TFE treatment. TFE also increased brown adipocyte expressions of the transcription factor Ucp1 and Prdm16 in whole tibiae. There was no detectible protein expression of brown adipocyte markers in the proximal tibia. Taken together, TFE regulation of bone marrow adiposity in OVX rats is mediated, at least in part, via maintaining the reciprocity of white and brown adipose tissue.