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Background: Changes in brain stiffness can be an important biomarker for neurological disease. Magnetic resonance elastography (MRE) quantifies tissue stiffness, but the results vary between acquisition and reconstruction methods., Purpose: To measure MRE repeatability and estimate the effect of different reconstruction methods and varying data quality on estimated brain stiffness., Study Type: Prospective., Subjects: Fifteen healthy subjects., Field Strength/sequence: 3T MRI, gradient-echo elastography sequence with a 50 Hz vibration frequency., Assessment: Imaging was performed twice in each subject. Images were reconstructed using a curl-based and a finite-element-model (FEM)-based method. Stiffness was measured in the whole brain, in white matter, and in four cortical and four deep gray matter regions. Repeatability coefficients (RC), intraclass correlation coefficients (ICC), and coefficients of variation (CV) were calculated. MRE data quality was quantified by the ratio between shear waves and compressional waves., Statistical Tests: Median values with range are presented. Reconstruction methods were compared using paired Wilcoxon signed-rank tests, and Spearman's rank correlation was calculated between MRE data quality and stiffness. Holm-Bonferroni corrections were employed to adjust for multiple comparisons., Results: In the whole brain, CV was 4.3% and 3.8% for the curl and the FEM reconstruction, respectively, with 4.0-12.8% for subregions. Whole-brain ICC was 0.60-0.74, ranging from 0.20 to 0.89 in different regions. RC for the whole brain was 0.14 kPa and 0.17 kPa for the curl and FEM methods, respectively. FEM reconstruction resulted in 39% higher stiffness than the curl reconstruction (P < 0.05). MRE data quality, defined as shear-compression wave ratio, was higher in peripheral regions than in central regions of the brain (P < 0.05). No significant correlations were observed between MRE data quality and stiffness estimates., Data Conclusion: MRE of the human brain is a robust technique in terms of repeatability. Caution is warranted when comparing stiffness values obtained with different techniques., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 1., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Grant Support: This project was funded by the Research Council of Norway., Background: Oxygen uptake through the gastrointestinal tract after oral administration of oxygenated water in humans is not well studied and is debated in the literature. Due to the paramagnetic properties of oxygen and deoxyhemoglobin, MRI as a technique might be able to detect changes in relaxometry values caused by increased oxygen levels in the blood., Purpose: To assess whether oxygen dissolved in water is absorbed from the gastrointestinal tract and transported into the bloodstream after oral administration., Study Type: A randomized, double-blinded, placebo-controlled crossover trial., Population/subjects: Thirty healthy male volunteers age 20-35., Field Strength/sequence: 3T/Modified Look-Locker inversion recovery (MOLLI) T 1 -mapping and multi fast field echo (mFFE) T 2 *-mapping., Assessment: Each volunteer was scanned in two separate sessions. T 1 and T 2 * maps were acquired repeatedly covering the hepatic portal vein (HPV) and vena cava inferior (VCI, control vein) before and after intake of oxygenated or control water. Assessments were done by placing a region of interest in the HPV and VCI., Statistical Test: A mixed linear model was performed to the compare control vs. oxygen group., Results: Drinking caused a mean 1.6% 95% CI (1.1-2.0% P < 0.001) increase in T 1 of HPV blood and water oxygenation attributed another 0.70% 95% confidence interval (CI) (0.07-1.3% P = 0.028) increase. Oxygenation did not change T 1 in VCI blood. Mean T 2 * increased 9.6% 95% CI (1.7-17.5% P = 0.017) after ingestion of oxygenated water and 1.2% 95% CI (-4.3-6.8% P = 0.661) after ingestion of control water. The corresponding changes in VCI blood were not significant., Data Conclusion: Ingestion of water caused changes in T 1 and T 2 * of HPV blood compatible with dilution due to water absorption. The effects were enhanced by oxygen. Assessment of oxygen enrichment of HPV blood was not possible due to the dilution effect., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:720-728., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: To investigate the sensitivity of modified Look-Locker inversion recovery (MOLLI) to measure changes in dissolved oxygen (DO) concentrations in water samples and to calculate sequence-specific relaxivity (r 1m ) and limit of detection (LOD)., Materials and Methods: Ten water samples with a range of DO concentrations were scanned at 3 T using two variations of MOLLI schemes. Using linear regression the r 1 of DO was estimated from the measured DO concentrations and T 1 relaxation rates (R 1 ). The results were combined with previously reported values on in vivo stability measures of the MOLLI sequences and used to estimate a LOD., Results: DO concentrations ranged from 0.5 to 21.6 mg L -1 . A linear correlation between DO and R 1 was obtained with both MOLLI sequences, with an average correlation coefficient (R 2 ) 0.9 and an average estimated r 1 ([Formula: see text]) of 4.45 × 10 -3  s -1  mg -1  L. Estimated LOD was ≈ 10 mg L -1 ., Conclusion: MOLLI T 1 -mapping sequences may be used for detecting dissolved oxygen in vivo at 3 T with an [Formula: see text] in the range 4.18-4.8 × 10 -3  s -1  mg -1  L and a corresponding LOD for dissolved oxygen of approximately 10 mg L -1 . MOLLI-based T 1 mapping may be a useful non-invasive tool for quantification of in vivo changes of DO concentration during oxygen challenges.

Objective: To investigate the effects of a range of parameter settings on T 1 measurement stability in the portal vein using the T1-mapping sequences Look-Locker (LL) and Modified Look-Locker inversion recovery (MOLLI)., Materials and Methods: Ten different versions of LL and MOLLI sequences were tested and compared to a reference sequence provided by the MR manufacturer. Ten healthy volunteers were imaged multiple times on two separate scan days at 3T. The mean T 1 values and coefficient of variation (CoV) were calculated for each of the ten sequences and compared to the reference sequence., Results: Six of the tested sequences had T 1 values close to the reference sequence; among those, three sequences achieved lower CoV than the reference sequence. Lowest CoV was achieved using a non-triggered LL sequence with 5 beat readout and a 45 o flip angle (mean T 1 1733 ms ± 89 ms, CoV 1.3% ± 0.58%)., Conclusion: T 1 -measurements in the hepatic portal vein can be performed with high precision using either MOLLI or LL sequences provided that LL sampling duration is sufficiently long and flip angle sufficiently high. The advantage of constant timing outweighed the advantage of ECG-triggering.

Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade., Methods and Results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003)., Conclusions: Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume.

Purpose: To implement a dynamic contrast-based multi-echo MRI sequence in assessment of rectal cancer and evaluate associations between histopathologic data and the acquired dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) -MRI parameters., Materials and Methods: This pilot study reports results from 17 patients with resectable rectal cancer. Dynamic contrast-based multi-echo MRI (1.5T) was acquired using a three-dimensional multi-shot EPI sequence, yielding both DCE- and DSC-data following a single injection of contrast agent. The Institutional Review Board approved the study and all patients provided written informed consent. Quantitative analysis was performed by pharmacokinetic modeling on DCE data and tracer kinetic modeling on DSC data. Mann-Whitney U-test and receiver operating characteristics curve statistics was used to evaluate associations between histopathologic data and the acquired DCE- and DSC-MRI parameters., Results: For patients with histologically confirmed nodal metastasis, the primary tumor demonstrated a significantly lower K trans and peak change in R2*, R2*-peak enh , than patients without nodal metastasis, showing a P-value of 0.010 and 0.005 for reader 1, and 0.043 and 0.019 for reader 2, respectively., Conclusion: This study shows the feasibility of acquiring DCE- and DSC-MRI in rectal cancer by dynamic multi-echo MRI. A significant association was found between both K trans and R2*-peak enh in the primary tumor and histological nodal status of the surgical specimen, which may improve stratification of patients to intensified multimodal treatment., Level of Evidence: 4 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:194-206., (© 2016 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Overweight and obesity lead to changes in adipose tissue such as inflammation and reduced insulin sensitivity. The aim of this study was to assess how altered energy balance by reduced food intake or enhanced physical activity affect these processes. We studied sedentary subjects with overweight/obesity in two intervention studies, each lasting 12 weeks affecting energy balance either by energy restriction (~20% reduced intake of energy from food) in one group, or by enhanced energy expenditure due to physical exercise (combined endurance- and strength-training) in the other group. We monitored mRNA expression by microarray and mRNA sequencing from adipose tissue biopsies. We also measured several plasma parameters as well as fat distribution with magnetic resonance imaging and spectroscopy. Comparison of microarray and mRNA sequencing showed strong correlations, which were also confirmed using RT-PCR In the energy restricted subjects (body weight reduced by 5% during a 12 weeks intervention), there were clear signs of enhanced lipolysis as monitored by mRNA in adipose tissue as well as plasma concentration of free-fatty acids. This increase was strongly related to increased expression of markers for M1-like macrophages in adipose tissue. In the exercising subjects (glucose infusion rate increased by 29% during a 12-week intervention), there was a marked reduction in the expression of markers of M2-like macrophages and T cells, suggesting that physical exercise was especially important for reducing inflammation in adipose tissue with insignificant reduction in total body weight. Our data indicate that energy restriction and physical exercise affect energy-related pathways as well as inflammatory processes in different ways, probably related to macrophages in adipose tissue., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Aims: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation., Methods and Results: In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI -0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed., Conclusion: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: To test the split dynamic magnetic resonance imaging (MRI) technique in the assessment of breast masses in which high spatial resolution and dual-echo high temporal resolution data are acquired during a single bolus injection., Materials and Methods: Forty-four women with breast masses were examined using split dynamic MRI. Quantitative analysis was performed with pharmacokinetic modeling on T1 -weighted images and estimation of maximum peak change in R2 * images (R2 *-peakenh ). High spatial resolution data were interpreted by two radiologists using the Breast Imaging Reporting and Data System (BI-RADS). Mann-Whitney tests were used to determine the parameters ability for establishing or excluding malignancy. For both readers, diagnostic accuracy, with and without information from the quantitative analysis, was determined using receiver operating characteristic (ROC) analysis, and evaluated using pairwise comparison of the areas under the ROC curve (Az ) and McNemar tests., Results: Significant parameters for establishing or excluding malignancy were R2 *-peakenh (P < 0.001), plasma volume (P = 0.006), and time-to-peak enhancement (P = 0.003) showing an Az of 0.928 combined. For one out of the two readers, diagnostic accuracy was significantly improved when adding quantitative kinetic analysis to the BI-RADS score (P = 0.017)., Conclusion: High temporal resolution T1 -weighted and R2 * dynamic information combined with BI-RADS interpretations improved the diagnostic performance in differentiating malignant from benign breast masses compared to BI-RADS interpretations alone., (© 2014 Wiley Periodicals, Inc.)

Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12-week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real-time PCR of mRNA of lipid droplet-associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large-scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training., (© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Purpose: To test the feasibility of a novel "split dynamic" method in which high temporal and high spatial resolution dynamic MR images are acquired during a single bolus injection., Materials and Methods: High temporal resolution images were acquired using a three-dimensional (3D) dual-echo EPI sequence. The high spatial resolution images were acquired using a 3D T1 -weighted turbo field echo sequence. Simulations were performed to test the split dynamic method in terms of accuracy relative to a continuous acquisition and for temporal sampling requirements for accurate estimation of kinetic parameters. The method was tested in four patients where pharmacokinetic parameters were extracted from the high temporal resolution data., Results: The split dynamic method enabled quantitative evaluation of both T1- and T2*-weighted characteristics. Simulations showed that splitting the dynamic acquisition does not significantly influence the reliability of parameter estimations. Simulation showed a required temporal resolution of 13, 16, and 8 s for accurate estimates of Ktrans, ve, and vp, respectively, and an optimal sampling interval between 2 and 6 s for peak R2*., Conclusion: The split dynamic sequence enabled detailed assessment of dynamic T1- and T2*-weighted contrast kinetics without compromising guidelines concerning spatial resolution., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To investigate the contrast of three-dimensional balanced steady state free precession (3D bSSFP) in the two component T2 model and to apply the results to optimize 3D bSSFP for prostate imaging at 1.5 Tesla., Materials and Methods: In each of seven healthy volunteers, six 3D bSSFP acquisitions were performed with flip angles (alpha) equally spaced between 10 degrees and 110 degrees . Predictions of signal and contrast were obtained from synthetic bSSFP images calculated from relaxation parameters obtained from a multi-spin-echo acquisition. One biexponential and two monoexponential models were applied. Measured and predicted signals were compared by simple linear regression., Results: The measured contrast to signal ratio increased continuously with alpha. Mean R(2) for the biexponential model was almost constant for alpha in the range 50-110 degrees . The biexponential model was a better predictor of the measured signal than the monoexponential model. A monoexponential model restricted to the echoes TE = 50-125 ms performed similar to the biexponential model. The predicted contrast peaked at alpha between 50 degrees and 90 degrees ., Conclusion: Prostate imaging with bSSFP benefited from high flip angles. The biexponential model provided good signal prediction while predictions from the monoexponential models are dependent on the range of TE used for T2 determination., (Copyright 2010 Wiley-Liss, Inc.)

Purpose: To investigate the T2 decay in prostate tissue for multiexponentiality and to assess how the biexponential model relates to established T2W contrast., Materials and Methods: A 32-echo spin-echo sequence was performed on 16 volunteers. Six single-voxel decay curves were sampled from each prostate. Prediction accuracies were assessed by jackknifing for the mono-, bi-, and triexponential models. The differences were evaluated by cross-validated analysis of variance (CVANOVA). Multiple linear regression was performed to assess the relation between parameters in the biexponential model and the contrast in T2W images., Results: Mono-, bi-, and triexponential models were preferred in 8 (10%), 72 (86%), and 4 (5%) cases, respectively. The biexponential short T2 was 64 msec (range 43 to 92 msec) and the long T2 was 490 msec (range 161 to 1319 msec). The fitted signal fraction, f, of the long T2 component was 27% (range 3% to 80%). The adjusted R(2) was 75.1% for the full regression model and decreased by 0.9%, 1.3%, and 39.2% when short T2, long T2, and f were removed from the model, respectively., Conclusion: Prostatic T2 decay was, in general, biexponential. The differences between the T2 components were large enough for accurate quantification. The T2W image contrast was primarily predicted by the biexponential signal fractions., (Copyright (c) 2008 Wiley-Liss, Inc.)