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.

CT-based deep learning model for predicting hospital discharge outcome in spontaneous intracerebral hemorrhage.

OBJECTIVES: To predict the functional outcome of patients with intracerebral hemorrhage (ICH) using deep learning models based on computed tomography (CT) images. METHODS: A retrospective, bi-center study of ICH patients was conducted. Firstly, a custom 3D convolutional model was built for predicting the functional outcome of ICH patients based on CT scans from randomly selected ICH patients in H training dataset collected from H hospital. Secondly, clinical data and radiological features were collected at admission and the Extreme Gradient Boosting (XGBoost) algorithm was used to establish a second model, named the XGBoost model. Finally, the Convolution model and XGBoost model were fused to build the third "Fusion model." Favorable outcome was defined as modified Rankin Scale score of 0-3 at discharge. The prognostic predictive accuracy of the three models was evaluated using an H test dataset and an external Y dataset, and compared with the performance of ICH score and ICH grading scale (ICH-GS). RESULTS: A total of 604 patients with ICH were included in this study, of which 450 patients were in the H training dataset, 50 patients in the H test dataset, and 104 patients in the Y dataset. In the Y dataset, the areas under the curve (AUCs) of the Convolution model, XGBoost model, and Fusion model were 0.829, 0.871, and 0.905, respectively. The Fusion model prognostic performance exceeded that of ICH score and ICH-GS (p = 0.043 and p = 0.045, respectively). CONCLUSIONS: Deep learning models have good accuracy for predicting functional outcome of patients with spontaneous intracerebral hemorrhage. CLINICAL RELEVANCE STATEMENT: The proposed deep learning Fusion model may assist clinicians in predicting functional outcome and developing treatment strategies, thereby improving the survival and quality of life of patients with spontaneous intracerebral hemorrhage. KEY POINTS: • Integrating clinical presentations, CT images, and radiological features to establish deep learning model for functional outcome prediction of patients with intracerebral hemorrhage. • Deep learning applied to CT images provides great help in prognosing functional outcome of intracerebral hemorrhage patients. • The developed deep learning model performs better than clinical prognostic scores in predicting functional outcome of patients with intracerebral hemorrhage.

Comparison of Sensory Observation and Somatosensory Stimulation in Mirror Neurons and the Sensorimotor Network: A Task-Based fMRI Study.

Objective: This study aimed to investigate brain plasticity by somatosensory stimulation (SS) and sensory observation (SO) based on mirror neuron and embodied cognition theory. Action observation therapy has been widely adopted for motor function improvement in post-stroke patients. However, it is uncertain whether the SO approach can also contribute to the recovery of sensorimotor function after stroke. In this study, we explored the therapeutic potential of SO for sensorimotor dysfunction and provided new evidence for neurorehabilitation. Methods: Twenty-six healthy right-handed adults (12 men and 14 women), aged 18-27 (mean, 22.12; SD, 2.12) years were included. All subjects were evaluated with task-based functional magnetic resonance imaging (fMRI) to discover the characteristics and differences in brain activation between SO and SS. We adopted a block design with two conditions during fMRI scanning: observing a sensory video of brushing (task condition A, defined as SO) and brushing subjects' right forearms while they watched a nonsense string (task condition B, defined as SS). One-sample t-tests were performed to identify brain regions and voxels activated for each task condition. A paired-sample t-test and conjunction analysis were performed to explore the differences and similarities between SO and SS. Results: The task-based fMRI showed that the bilateral postcentral gyrus, left precentral gyrus, bilateral middle temporal gyrus, right supramarginal gyrus, and left supplementary motor area were significantly activated during SO or SS. In addition to these brain regions, SO could also activate areas containing mirror neurons, like the left inferior parietal gyrus. Conclusion: SO could activate mirror neurons and sensorimotor network-related brain regions in healthy subjects like SS. Therefore, SO may be a promising novel therapeutic approach for sensorimotor dysfunction recovery in post-stroke patients.

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.

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.

Adding marrow R2∗ to proton density fat fraction improves the discrimination of osteopenia and osteoporosis in postmenopausal women assessed with 3D FACT sequence.

OBJECTIVE: To evaluate the role of three-dimensional Fat Analysis & Calculation Technique sequence in improving the diagnostic accuracy for the detection of osteopenia and osteoporosis by simultaneous quantification of proton density fat fraction (PDFF) and fat-corrected R2∗. METHODS: Fat Analysis & Calculation Technique imaging of lumbar spine was obtained in 99 postmenopausal women including 52 normal bone mass, 29 osteopenia, and 18 osteoporosis. The diagnostic performance of PDFF and R2∗ in the differentiation of different bone-density groups was evaluated with the receiver operating characteristic curve. RESULTS: The reproducibility of PDFF and R2∗ measures was satisfactory with the root mean square coefficient of variation, 2.16% and 2.70%, respectively. The intra- and interobserver agreements for the PDFF and R2∗ were excellent with the intraclass correlation coefficient > 0.9 for all. There were significant differences in PDFF and R2∗ among the three groups (P < 0.05). Bone density had a moderate inverse correlation with PDFF (r  = -0.659) but a positive association with R2∗ (r = 0.508, P < 0.001). Adjusted for age, years since menopause and body mass index, odds ratios (95% confidence interval) for osteopenia and osteoporosis per standard deviation higher marrow PDFF and R2∗ were 2.9 (1.4-5.8) and 0.4 (0.2-0.8), respectively. The areas under the curve were 0.821 for PDFF, 0.784 for R2∗, and 0.922 for both combined for the detection of osteoporosis (P < 0.05). Similar results were obtained in distinguishing osteopenia from healthy controls. CONCLUSIONS: Simultaneous estimation of marrow R2∗ and PDFF improves the discrimination of osteopenia and osteoporosis in comparison with the PDFF or R2∗ alone.

Marrow adiposity as an indicator for insulin resistance in postmenopausal women with newly diagnosed type 2 diabetes - an investigation by chemical shift-encoded water-fat MRI.

BACKGROUND: Marrow fat accumulates in diabetic conditions but remains elusive. The published works on the relationships between marrow fat phenotypes and glucose homeostasis are controversial. PURPOSE: To detect the association of insulin resistance with marrow adiposity in postmenopausal women with newly diagnosed type 2 diabetes (T2D) using chemical shift-encoded water-fat MRI. METHODS: We measured vertebral proton density fat fraction (PDFF) by 3T-MRI in 75 newly diagnosed T2D and 20 nondiabetic postmenopausal women. Bone mineral density (BMD), whole body fat mass and lean mass were determined by dual-energy X-ray absorptiometry. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Lumbar spine PDFF was higher in women with T2D (65.9 ± 6.8%) than those without diabetes (59.5 ± 6.1%, P = 0.009). There was a consistent inverse association between the vertebral PDFF and BMD. PDFF had a positive association with glycated hemoglobin and HOMA-IR but not with fasting plasma glucose and insulin. PDFF was significantly increased, and BMD was decreased in a linear trend from the lowest (<1.90) to highest (≥2.77) HOMA-IR quartile. Multivariate linear regression analyses revealed a positive association between log-transformed HOMA-IR and PDFF after adjustment for multiple covariates (ß = 0.382, P < 0.001). The positive association of HOMA-IR with PDFF remained robust when total body lean mass and fat mass, BMD was entered into the multivariate regression model, respectively (ß = 0.293 and ß = 0.251, respectively; all P <0.05). CONCLUSIONS: Elevated HOMA-IR was linked to higher marrow fat fraction in postmenopausal women with newly diagnosed T2D independently of body compositions.

Association between insulin resistance and the magnetic resonance spectroscopy-determined marrow fat fraction in nondiabetic postmenopausal women.

OBJECTIVE: The clinical consequences of insulin resistance and hyperinsulinemia on marrow lipid remain elusive. We aimed to explore the effects of anthropometric and biochemical measures, that is, estimates of insulin resistance, on marrow lipid accumulation in nondiabetic postmenopausal women using magnetic resonance (MR) spectroscopy. METHODS: The study participants were 91 nondiabetic postmenopausal women. Marrow fat fraction (FF) at the L3 vertebral body by single-voxel MR spectroscopy and bone mineral density (BMD) by dual-energy x-ray absorptiometry were measured. Their glucose and lipid metabolism were determined by biochemical analysis, and their insulin sensitivity was evaluated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Adjusted for multiple covariates including age, years since menopause, body mass index, alcohol intake, tobacco use, physical activity, and serum lipid profile, the mean FF was significantly increased, and BMD at the lumbar spine, femoral neck, and total hip decreased as quartiles of HOMA-IR increased (P for trends <0.01). HOMA-IR had a positive association with FF (mean difference 0.300, P < 0.001) and a negative association with BMD at the lumbar spine (mean difference -0.182, P = 0.016), total hip (mean difference -0.219, P = 0.001), and femoral neck (mean difference -0.195, P = 0.013). The above described associations of HOMA-IR with FF, lumbar spine, and total hip BMD remained essentially unchanged; however, the association with femoral neck BMD lost significance after adjusting for the aforementioned confounders. CONCLUSION: In nondiabetic postmenopausal women, insulin resistance is correlated with marrow lipid expansion. This association persists after adjusting for the body mass index and other potential covariates, suggesting an independent effect of insulin resistance on marrow adiposity.

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care.

Quantitative susceptibility mapping (QSM) has enabled magnetic resonance imaging (MRI) of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:951-971.

Magnetic Resonance Spectroscopy-Detected Change in Marrow Adiposity Is Strongly Correlated to Postmenopausal Breast Cancer Risk.

PURPOSE: To determine whether marrow fat fraction (FF) is correlated with postmenopausal breast cancer risk and clinicopathological characteristics of breast cancer. METHODS: Fifty-six patients with newly diagnosed and histologically confirmed postmenopausal breast cancer and 56 healthy controls underwent serologic test and magnetic resonance spectroscopy-based FF measurements. Data were analyzed by logistic multivariate regression models to determine the independent predictors of breast cancer risk and clinicopathological characters of breast cancer. RESULTS: Patients with breast cancer had higher FF than that of the controls. Marrow FF showed positive association with serum leptin levels (r = 0.607, P < .001) in the cases, but no relationship was found in the controls. In the univariate analysis, both levels of leptin and marrow FF were significantly associated with breast cancer risk and clinicopathological characteristics of breast cancer. In the multivariable model with adjustment for established breast cancer risk factors, serum leptin was a significant predictor of breast cancer risk (OR 1.746; 95% CI, 1.226-2.556) and clinicopathological characteristics of breast cancer including TNM, tumor size, lymph node status, and histological grade (OR 1.461-1.695); but when marrow FF was additionally added to the regression model, marrow FF but not leptin levels was observed to be an independent risk factor for breast cancer risk (OR 1.940; 95% CI, 1.306-2.910) and clinicopathological characteristics of breast cancer (OR 1.770-1.903). CONCLUSION: Marrow adiposity is a predictor of postmenopausal breast cancer risk and clinicopathological characteristics of breast cancer.

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.

To assess differential features of marrow adiposity between postmenopausal women with osteoarthritis and osteoporosis using water/fat MRI.

OBJECTIVE: To assess the differential features of marrow adiposity between osteoarthritis (OA) and osteoporosis (OP) in postmenopausal women using water/fat MRI. METHODS: This cross-sectional study included 97 postmenopausal women (OA [n = 25], OA + osteopenia [n = 27], OA + OP [n = 23], and OP groups [n = 22]). Water/fat MRI, dual-energy x-ray absorptiometry and biochemical analysis were performed to assess vertebral marrow fat fraction, bone mineral density, and bone biomarkers, respectively. Harris Hip Score was recorded to evaluate hip function. RESULTS: There were significant differences in marrow fat content among the OA, OA + osteopenia, and OA + OP groups, between OP and OA participants with normal bone mass or osteopenia (all P < 0.05); no significant difference was observed between OA + OP and OP groups. Serum levels of leptin and ß-Crosslaps in OA with normal bone mass and osteopenic OA groups were higher than in OP group. Marrow fat fraction was inversely correlated with Harris Hip Score (r = -0.371, P = 0.013), bone mineral density (r = -0.554, P = 0.009) and leptin levels (r = -0.610, P < 0.001). In multivariate regression analysis, marrow fat fraction was found to have a consistent and unchanged inverse association with leptin levels (Sß = -0.311, P = 0.002) and bone mineral density (Sß =  -0.265, P = 0.006) after adjusting for age, years since menopause, and body mass index. CONCLUSIONS: Postmenopausal OA with OP have a phenotype with higher marrow adiposity. OA and OP could coexist, for the presence of a specific subgroup of OA with increased marrow fat accumulation and high risk of developing OP.

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.

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.

Longitudinal assessment of marrow fat content using three-point Dixon technique in osteoporotic rabbits.

OBJECTIVE: In this longitudinal pilot study, we aimed to investigate the intra-, interobserver, and scan-rescan reproducibility of marrow fat fraction (FF) measurements using three-point Dixon imaging in osteoporotic rabbits: comparison with histopathology. METHODS: Twenty female rabbits were randomly assigned to sham-operation and ovariectomy in combination with daily methylprednisolone hemisuccinate groups (n = 10 per group). Marrow FF by three-point Dixon technique and bone density by dual-energy x-ray absorptiometry were assessed at baseline, 6 and 12 weeks after operation. Intra-, inter-reader, and scan-rescan reliability of FF measurements were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman 95% limit of agreement. Histomorphometry was performed to quantify marrow adipocyte parameters. RESULTS: Intra- and inter-reader reproducibility of FF measurements was "substantial" (ICC = 0.984 and 0.978, respectively). Although the ICC for scan-rescan reliability was excellent (ICC = 0.962), increased measurement variability was observed using Bland-Altman plot. Relative to the sham-operated rabbits, the adipocytes mean diameter, density, and percent adipocytes area in the osteoporotic rabbits increased by 23.4%, 68.9%, and 117.0%, respectively. Marrow FF was positively correlated with the quantitative parameters of adipocytes, particularly with percent adipocyte area, but inversely associated with bone density. At the relatively early stage, the percentage of bone loss was similar to that of elevated fatty marrow in the osteoporotic rabbits; at the later stage, the change for the latter outweighed that of the former. CONCLUSIONS: Results of three-point Dixon technique demonstrated a very reproducible manner within and between observers and acceptable scan-rescan performance in the assessment of marrow fat in rabbits.

Quantitative Susceptibility Mapping of Intracerebral Hemorrhages at Various Stages.

PURPOSE: To investigate the magnetic susceptibility of intracerebral hemorrhages (ICH) at various stages by applying quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Blood susceptibility was measured serially using QSM after venous blood withdrawal from healthy subjects. Forty-two patients who provided written consent were recruited in this Institutional Review Board-approved study. Gradient echo magnetic resonance imaging (MRI) data of the 42 patients (17 females; 64 ± 12 years) with ICH were processed with QSM. The susceptibilities of various blood products within hematomas were measured on QSM. RESULTS: Blood susceptibility continually increased and reached a plateau 96 hours after venous blood withdrawal. Hematomas at all stages were consistently hyperintense on QSM. Susceptibility was 0.57 ± 0.48, 1.30 ± 0.33, 1.14 ± 0.46, 0.40 ± 0.13, and 0.71 ± 0.31 ppm for hyperacute, acute, early subacute, late subacute, and chronic stages of hematomas, respectively. The susceptibility decrease from early subacute (1.14 ppm) to late subacute (0.4 ppm) was significant (P < 0.01). CONCLUSION: QSM reveals positive susceptibility in hyperacute hematomas, indicating that even at their hyperacute stage, deoxyhemoglobin may exist throughout the hematoma volume, not just at its rim, as seen on conventional T2* imaging. QSM also reveals a reduction of susceptibility from early subacute to late subacute ICH, suggesting that methemoglobin concentration decreases at the late subacute stage. J. Magn. Reson. Imaging 2016;44:420-425.

Panax notoginseng saponins mitigate ovariectomy-induced bone loss and inhibit marrow adiposity in rats.

OBJECTIVE: Previous data have suggested that Panax notoginseng saponins (PNS) can prevent estrogen deficiency-induced bone loss by dual action: stimulation of new bone formation and inhibition of bone resorption. Marrow adipogenesis has been identified as a negative indicator of skeletal strength and integrity. This study assessed the effects of early PNS supplementation on bone microarchitecture preservation and marrow fat content in an ovariectomized rat model. METHODS: Forty adult female Sprague-Dawley rats were randomly assigned to four equal groups for 12 weeks of treatment: (1) sham operation (SHAM) + vehicle; (2) ovariectomy (OVX) + vehicle; (3) OVX + 17ß-estradiol (25 µg/kg); (4) OVX + PNS (300 mg/kg/d, PO). Marrow fat content of the femur was determined, using fat/water magnetic resonance imaging (MRI), at baseline and 6 and 12 weeks after operation. At the end of the experiment, bone turnover, trabecular microarchitecture, and marrow adipocytes were assessed by serum biomarkers, micro-computed tomography (micro-CT), and histopathology, respectively. The effects of PNS on adipocytic differentiation were reflected by expression levels of the adipogenic genes PPARγ2 and C/EBPα, as determined by reverse transcription-polymerase chain reaction. RESULTS: Ovariectomized rats experienced remarkable increases in marrow fat content across time points, which were accompanied by elevated rate of bone turnover, global volumetric bone density, and trabecular microarchitecture deterioration. These OVX-induced pathological changes are reversible in that most of them could be mostly corrected upon 17ß-estradiol treatment. PNS treatment significantly reduced marrow adipogenesis (adipocyte density, -27.2%; size, -22.7%; adipocyte volume-to-tissue volume ratio, -53.3%; all P < 0.01) and adipocyte marker gene expression, and prevented bone mass loss and microarchitecture deterioration. Moreover, PNS enhanced osteoblast activity but suppressed osteoclast turnover, as evidenced by decreased levels of serum C-terminal telopeptides of type I collagen and elevated levels of alkaline phosphatase. CONCLUSIONS: PNS mitigates estrogen deficiency-induced deterioration of trabecular microarchitecture and suppresses marrow adipogenesis.

Phase-corrected bipolar gradients in multi-echo gradient-echo sequences for quantitative susceptibility mapping.

OBJECTIVE: Large echo spacing of unipolar readout gradients in current multi-echo gradient-echo (GRE) sequences for mapping fields in quantitative susceptibility mapping (QSM) can be reduced using bipolar readout gradients thereby improving acquisition efficiency. MATERIALS AND METHODS: Phase discrepancies between odd and even echoes in the bipolar readout gradients caused by non-ideal gradient behaviors were measured, modeled as polynomials in space and corrected for accordingly in field mapping. The bipolar approach for multi-echo GRE field mapping was compared with the unipolar approach for QSM. RESULTS: The odd-even-echo phase discrepancies were approximately constant along the phase encoding direction and linear along the readout and slice-selection directions. A simple linear phase correction in all three spatial directions was shown to enable accurate QSM of the human brain using a bipolar multi-echo GRE sequence. Bipolar multi-echo acquisition provides QSM in good quantitative agreement with unipolar acquisition while also reducing noise. CONCLUSION: With a linear phase correction between odd-even echoes, bipolar readout gradients can be used in multi-echo GRE sequences for QSM.

Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats.

Although the primary target cell of bisphosphonates is the osteoclast, increasing attention is being given to other effector cells influenced by bisphosphonates, such as osteoblasts and marrow adipocytes. Early zoledronic acid (ZA) treatment to ovariectomized (OVX) rats has been found to fully preserve bone microarchitecture over time. However, little is known regarding the influence of ZA on marrow adipogenesis. The purpose of this study was to monitor the ability of early administration of ZA in restoring marrow adiposity in an estrogen-deficient rat model. Thirty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX + vehicle, and OVX + ZA groups (n=10/group). Dual-energy x-ray absorptiometry and water/fat magnetic resonance imaging were performed at baseline, 6 weeks, and 12 weeks after treatment to assess bone mineral density and marrow fat fraction. Serum biochemical markers, bone remodeling, and marrow adipocyte parameters were analyzed using biochemistry, histomorphometry, and histopathology, respectively. The expression levels of osteoblast, adipocyte, and osteoclast-related genes in bone marrow were assessed using RT-PCR. The OVX rats showed marked bone loss, first detected at 12 weeks, but estrogen deficiency resulted in a remarked increase in marrow fat fraction, first detected at 6 weeks compared with the SHAM rats (all P < .001). Similarly, the OVX rats had a substantially larger percent adipocyte area (+163.0%), mean diameter (+29.5%), and higher density (+57.3%) relative to the SHAM rats. Bone histomorphometry, levels of osteoclast-related gene expression, and a serum resorption marker confirmed that ZA significantly suppressed bone resorption activities. Furthermore, ZA treatment returned adipocyte-related gene expression and marrow adipocyte parameters toward SHAM levels. These data suggest that a single dose of early ZA treatment acts to reverse marrow adipogenesis occurring during estrogen deficiency, which may contribute to its capacity to reduce bone loss.

Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis.

OBJECTIVE: Icariin prevents bone loss by stimulating new bone formation and by inhibiting bone resorption. However, less is known about how icariin affects marrow adiposity. This lack of information is a vital problem, as the degree of marrow adipogenesis may be an alternative indicator of the severity of osteoporosis in relation to the degree of osteogenesis and osteoblastogenesis. To explore this question, we tested the effects of icariin on bone mineral density (BMD) and marrow fat content in a rat model of postmenopausal osteoporosis. METHODS: Thirty-six 3-month-old female Sprague-Dawley rats were randomly assigned to one of the following treatment groups: sham operation, ovariectomized controls, and ovariectomized rats treated orally with either 17ß-estradiol or icariin for 12 weeks. BMD and marrow fat fraction were dynamically measured on weeks 0, 6, and 12. After 12 weeks of treatment, serum 17ß-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. RESULTS: Ovariectomized controls experienced a marked increase in fat fraction over time, with increases of 40% between weeks 0 and 6 and 69.4% between weeks 6 and 12 (P < 0.001). Marrow adiposity in ovariectomized controls was dramatically higher than that in sham rats on week 6; however, a reduction in BMD was detected in ovariectomized rats on week 12 (P < 0.001). Ovariectomized rats had levels of serum alkaline phosphatase and serum C-terminal telopeptide of type I collagen that were 49.4% and 67.2% higher, respectively, than those of sham rats (P < 0.001). The density, size, and volume of marrow adipocytes in ovariectomized controls were 57.3%, 29.5%, and 163% higher, respectively, than those in sham rats. Early icariin treatment decreased bone biomarker levels, inhibited bone degeneration, and restored marrow fat infiltration and adipocyte parameters to the levels observed in sham rats. Overall, the osteoprotective effect of icariin was comparable with that of 17ß-estradiol; however, icariin did not produce uterine estrogenicity. CONCLUSIONS: Early icariin treatment restores marrow adiposity in the estrogen-deficient rat model.