Diffusion-weighted MR spectroscopy: Consensus, recommendations, and resources from acquisition to modeling.

Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion-weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations. Despite its great potential, dMRS remains a challenging technique on all levels: from the data acquisition to the analysis, quantification, modeling, and interpretation of results. These challenges were the motivation behind the organization of the Lorentz Center workshop on "Best Practices & Tools for Diffusion MR Spectroscopy" held in Leiden, the Netherlands, in September 2021. During the workshop, the dMRS community established a set of recommendations to execute robust dMRS studies. This paper provides a description of the steps needed for acquiring, processing, fitting, and modeling dMRS data, and provides links to useful resources.

Feasibility of omega-3 fatty acid fraction mapping using chemical shift encoding-based imaging at 3 T.

PURPOSE: The aim of this work is to develop an ω-3 fatty acid fraction mapping method at 3 T based on a chemical shift encoding model, to assess its performance in a phantom and in vitro study, and to further demonstrate its feasibility in vivo. METHODS: A signal model was heuristically derived based on spectral appearance and theoretical considerations of the corresponding molecular structures to differentiate between ω-3 and non-ω-3 fatty acid substituents in triacylglycerols in addition to the number of double bonds (ndb), the number of methylene-interrupted double bonds (nmidb), and the mean fatty acid chain length (CL). First, the signal model was validated using single-voxel spectroscopy and a time-interleaved multi-echo gradient-echo (TIMGRE) sequence in gas chromatography-mass spectrometry (GC-MS)-calibrated oil phantoms. Second, the TIMGRE-based method was validated in vitro in 21 adipose tissue samples with corresponding GC-MS measurements. Third, an in vivo feasibility study was performed for the TIMGRE-based method in the gluteal region of two healthy volunteers. Phantom and in vitro data was analyzed using a Bland-Altman analysis. RESULTS: Compared with GC-MS, MRS showed in the phantom study significant correlations in estimating the ω-3 fraction (p < 0.001), ndb (p < 0.001), nmidb (p < 0.001), and CL (p = 0.001); MRI showed in the phantom study significant correlations (all p < 0.001) for the ω-3 fraction, ndb, and nmidb, but no correlation for CL. Also in the in vitro study, significant correlations (all p < 0.001) between MRI and GC-MS were observed for the ω-3 fraction, ndb, and nmidb, but not for CL. An exemplary ROI measurement in vivo in the gluteal subcutaneous adipose tissue yielded (mean ± standard deviation) 0.8% ± 1.9% ω-3 fraction. CONCLUSION: The present study demonstrated strong correlations between gradient-echo imaging-based ω-3 fatty acid fraction mapping and GC-MS in the phantom and in vitro study. Furthermore, feasibility was demonstrated for characterizing adipose tissue in vivo.

Practical Application of Multivendor MRI-Based R2* Mapping for Liver Iron Quantification at 1.5 T and 3.0 T.

BACKGROUND: Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear. PURPOSE: To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions. STUDY TYPE: Prospective. SUBJECTS: Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers. FIELD STRENGTH/SEQUENCE: Standardized multiecho spoiled gradient echo sequence at 1.5 T and 3.0 T for R2* mapping and a multiple spin-echo sequence at 1.5 T for LIC quantification. MRI vendors: GE Healthcare, Philips Healthcare, and Siemens Healthineers. ASSESSMENT: R2* maps were generated using both the centralized and vendor reconstructions, and ranges of agreement were determined. R2*-LIC linear calibrations were determined for each site, field strength, and reconstruction and compared with the MCMV calibrations. STATISTICAL TESTS: Bland-Altman analysis to determine ranges of agreement. Linear regression, analysis of covariance F tests, and Tukey's multiple comparison testing to assess reproducibility of calibrations across sites and vendors. A P value <0.05 was considered significant. RESULTS: The upper limits of R2* ranges of agreement were approximately 500, 375, and 330 s-1 for GE, Philips, and Siemens reconstructions, respectively, at 1.5 T and approximately 700 and 800 s-1 for GE and Philips, respectively, at 3.0 T. Within the R2* ranges of agreement, vendor R2*-LIC calibrations demonstrated high reproducibility (no significant differences between slopes or intercepts; P ≥ 0.06) and agreed with the MCMV calibrations (overlapping 95% confidence intervals). DATA CONCLUSION: Based on the determined upper limits, R2* measurements obtained from vendor-provided R2* maps may be reliably and practically used to quantify LIC less than approximately 8-13 mg/g using the MCMV calibrations and similar acquisition parameters as this study. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Silicone implant and fibrous capsule assessment based on water-fat-silicone chemical shift encoding-based species separation in breast MRI.

BACKGROUND: With rising breast augmentations worldwide, there is an increasing clinical need for an early and accurate detection of implant complications. PURPOSE: To compare the quality of chemical shift encoding-based (CSE) water-fat-silicone separation compared to double inversion recovery (DIR) silicone-only imaging in breast magnetic resonance imaging (MRI). MATERIAL AND METHODS: This retrospective, single-center study included women with silicone implants subjected to 3-T MRI between January 2021 and March 2022. MRI included (i) two-dimensional silicone-only T2-weighted turbo spin echo DIR acquisition and (ii) three-dimensional CSE imaging based on multi-echo gradient-echo sequence enabling water-, fat-, and silicone-image separation. Images were evaluated and compared by three independent radiologists using a clinically established rating including differentiability of the silicone implant, visibility and contouring of the adjacent fibrous capsule, and accuracy of intralesional folds in a ranking of 1-5. The apparent contrast-to-noise (aCNR) was calculated. RESULTS: In 71 women, the average quality of water-fat-silicone images from CSE imaging was assessed as "good" (assessment 4 ± 0.9). In 68 (96%) patients, CSE imaging achieved a concise delineation of the silicone implant and precise visualization of the fibrous capsule that was not distinguishable in DIR imaging. Implant ruptures were more easily detected in CSE imaging. The aCNR was higher in CSE compared to DIR imaging (18.43 ± 9.8 vs. 14.73 ± 2.5; P = 0.002). CONCLUSION: Intrinsically co-registered water-fat-silicone-separated CSE-based images enable a reliable assessment of silicone implants. The simultaneously improved differentiability of the implant and fibrous capsule may provide clinicians with a valuable tool for an accurate evaluation of implant integrity and early detection of potential complications.

Multicenter Reproducibility of Liver Iron Quantification with 1.5-T and 3.0-T MRI.

Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using F tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic performance of R2* MRI in the detection of clinically relevant LIC thresholds. Results A total of 207 participants (mean age, 38 years ± 20 [SD]; 117 male participants) were evaluated between March 2015 and September 2019. A linear relationship was confirmed between R2* and LIC. All calibrations within the same field strength were highly reproducible, showing no evidence of statistically significant center-specific differences (P > .43 across all comparisons). Calibrations for 1.5 T and 3.0 T were generated, as follows: for 1.5 T, LIC (in milligrams per gram [dry weight]) = -0.16 + 2.603 × 10-2 R2* (in seconds-1); for 2.89 T, LIC (in milligrams per gram) = -0.03 + 1.400 × 10-2 R2* (in seconds-1); for 3.0 T, LIC (in milligrams per gram) = -0.03 + 1.349 × 10-2 R2* (in seconds-1). Liver R2* had high diagnostic performance in the detection of clinically relevant LIC thresholds (area under the ROC curve, >0.98). Conclusion R2* MRI enabled accurate and reproducible quantification of liver iron overload over clinically relevant ranges of liver iron concentration (LIC). The data generated in this study provide the necessary calibrations for broad clinical dissemination of R2*-based LIC quantification. ClinicalTrials.gov registration no.: NCT02025543 © RSNA, 2022 Online supplemental material is available for this article.

Assessing breast density using the chemical-shift encoding-based proton density fat fraction in 3-T MRI.

OBJECTIVES: There is a clinical need for a non-ionizing, quantitative assessment of breast density, as one of the strongest independent risk factors for breast cancer. This study aims to establish proton density fat fraction (PDFF) as a quantitative biomarker for fat tissue concentration in breast MRI and correlate mean breast PDFF to mammography. METHODS: In this retrospective study, 193 women were routinely subjected to 3-T MRI using a six-echo chemical shift encoding-based water-fat sequence. Water-fat separation was based on a signal model accounting for a single T2* decay and a pre-calibrated 7-peak fat spectrum resulting in volumetric fat-only, water-only images, PDFF- and T2*-values. After semi-automated breast segmentation, PDFF and T2* values were determined for the entire breast and fibroglandular tissue. The mammographic and MRI-based breast density was classified by visual estimation using the American College of Radiology Breast Imaging Reporting and Data System categories (ACR A-D). RESULTS: The PDFF negatively correlated with mammographic and MRI breast density measurements (Spearman rho: -0.74, p < .001) and revealed a significant distinction between all four ACR categories. Mean T2* of the fibroglandular tissue correlated with increasing ACR categories (Spearman rho: 0.34, p < .001). The PDFF of the fibroglandular tissue showed a correlation with age (Pearson rho: 0.56, p = .03). CONCLUSION: The proposed breast PDFF as an automated tissue fat concentration measurement is comparable with mammographic breast density estimations. Therefore, it is a promising approach to an accurate, user-independent, and non-ionizing breast density assessment that could be easily incorporated into clinical routine breast MRI exams. KEY POINTS: • The proposed PDFF strongly negatively correlates with visually determined mammographic and MRI-based breast density estimations and therefore allows for an accurate, non-ionizing, and user-independent breast density measurement. • In combination with T2*, the PDFF can be used to track structural alterations in the composition of breast tissue for an individualized risk assessment for breast cancer.

Single-voxel short-TR multi-TI multi-TE STEAM MRS for water-fat relaxometry.

PURPOSE: To propose a short-TR multi-TI multi-TE (SHORTIE, ['shȯr-te]) STEAM single-voxel MRS acquisition scheme for the simultaneous assessment of T1 relaxation, T2 relaxation, and the proton density fat fraction at reduced scan times when compared with conventional long-TR multi-TI STEAM and long-TR multi-TE STEAM single-voxel MRS. METHODS: Theoretical analysis for multi-TI (TI = 10, 100, 500, 1500 ms; scan time = 2:43 minutes), multi-TE (TE = 12, 15, 20, 25 ms; scan time = 2:24 minutes), and SHORTIE STEAM (all TI and TE combinations; scan time = 2:52 minutes) was carried out including Cramér-Rao lower bound and parameter estimation efficiency analysis for T1 (150-2000 ms) and T2 (5-150 ms) relaxation. The SHORTIE STEAM acquisition was compared with multi-TI STEAM and multi-TE STEAM in water-fat phantoms and in a human in vivo study of the adipose tissue depot in the supraclavicular fossa in 7 volunteers at 3 T. RESULTS: Cramér-Rao lower bound analysis revealed similar to increased variances for T1 and T2 estimators for SHORTIE STEAM. Parameter efficiency analysis demonstrated superior performance of SHORTIE, particularly for shorter T1 and T2 when compared with multi-TI STEAM and multi-TE STEAM. For the phantom data, linear regression and Bland-Altmann analysis yielded a slope/intercept/mean difference of 1.07/-15.40/-17.18 for T1 (in ms; r = 0.999), 0.93/+1.32/+1.09 for T2 (in ms; r = 0.995), and 0.98/-0.04/+0.78 for the fat fraction (in percent; r = 0.999); and for the in vivo data 1.08/+1.77/-62.2 for T1 (r = 0.994), 0.88/+6.69/-1.55 for T2 (r = 0.884), and 0.56/+34.40/-0.46 for the fat fraction (r = 0.673), respectively. CONCLUSION: The SHORTIE STEAM acquisition allows shorter scan times for the simultaneous probing of relaxation properties and spectral content in the water-fat environment when compared with combined long-TR multi-TI, and long-TR multi-TE STEAM.

Preconditioned water-fat total field inversion: Application to spine quantitative susceptibility mapping.

PURPOSE: To (a) develop a preconditioned water-fat total field inversion (wfTFI) algorithm that directly estimates the susceptibility map from complex multi-echo gradient echo data for water-fat regions and to (b) evaluate the performance of the proposed wfTFI quantitative susceptibility mapping (QSM) method in comparison with a local field inversion (LFI) method and a linear total field inversion (TFI) method in the spine. METHODS: Numerical simulations and in vivo spine multi-echo gradient echo measurements were performed to compare wfTFI to an algorithm based on disjoint background field removal (BFR) and LFI and to a formerly proposed TFI algorithm. The data from 1 healthy volunteer and 10 patients with metastatic bone disease were included in the analysis. Clinical routine computed tomography (CT) images were used as a reference standard to distinguish osteoblastic from osteolytic changes. The ability of the QSM methods to distinguish osteoblastic from osteolytic changes was evaluated. RESULTS: The proposed wfTFI method was able to decrease the normalized root mean square error compared to the LFI and TFI methods in the simulation. The in vivo wfTFI susceptibility maps showed reduced BFR artifacts, noise amplification, and streaking artifacts compared to the LFI and TFI maps. wfTFI provided a significantly higher diagnostic confidence in differentiating osteolytic and osteoblastic lesions in the spine compared to the LFI method (p = .012). CONCLUSION: The proposed wfTFI method can minimize BFR artifacts, noise amplification, and streaking artifacts in water-fat regions and can thus better differentiate between osteoblastic and osteolytic changes in patients with metastatic disease compared to LFI and the original TFI method.

Estimating vertebral bone marrow fat unsaturation based on short-TE STEAM MRS.

PURPOSE: To define a metric for the separability between water and olefinic fat peaks that defines a threshold beyond which the extraction of the olefinic fat peak from vertebral bone marrow short-echo time-stimulated echo acquisition mode MRS at 3T is feasible when using a constrained peak fitting based on the triglyceride fat model. METHODS: The water and olefinic peak height difference was defined as a metric for quantifying the separability of water and olefinic fat peaks. Fat unsaturation was determined using an unconstrained olefinic peak fitting and a constrained fitting of all fat peaks to the triglyceride model. The agreement between the two peak-fitting methods was used to define a threshold on water and olefinic peak height difference separating two groups (A and B), based on L5 short-echo time-stimulated echo acquisition mode (TE = 11 ms) spectra from 252 subjects measured at 3T. RESULTS: A threshold on water and olefinic peak height difference was defined. Group A with a good agreement of the olefinic fat peak between the two peak-fitting methods showed a mean number of double bounds = 2.95 ± 0.21, a mean number of methylene-interrupted double bounds = 0.94 ± 0.16 and also a significantly lower coefficient of variation for all fatty acid composition parameters compared to group B (p < .001). The water and olefinic peak height difference value showed an inverse association with fat fraction. CONCLUSION: A threshold of a metric quantifying the separability of the water peak and the olefinic fat peaks was defined for the estimation of the vertebral bone marrow fat unsaturation from short-echo time-stimulated echo acquisition mode MRS. The proposed methodology shows that the assessment of vertebral bone marrow unsaturation is feasible with a short-echo time-stimulated echo acquisition mode MRS in subjects with a higher fat fraction.

Lipid droplet-size mapping in human adipose tissue using a clinical 3T system.

PURPOSE: To develop a methodology for probing lipid droplet sizes with a clinical system based on a diffusion-weighted stimulated echo-prepared turbo spin-echo sequence and to validate the methodology in water-fat emulsions and show its applicability in ex vivo adipose-tissue samples. METHODS: A diffusion-weighted stimulated echo-prepared preparation was combined with a single-shot turbo spin-echo readout for measurements at different b-values and diffusion times. The droplet size was estimated with an analytical expression, and three fitting approaches were compared: magnitude-based spatial averaging with voxel-wise residual minimization, complex-based spatial averaging with voxel-wise residual minimization, and complex-based spatial averaging with neighborhood-regularized residual minimization. Simulations were performed to characterize the fitting residual landscape and the approaches' noise performance. The applicability was assessed in oil-in-water emulsions in comparison with laser deflection and in ten human white adipose tissue samples in comparison with histology. RESULTS: The fitting residual landscape showed a minimum valley with increasing extent as the droplet size increased. In phantoms, a very good agreement of the mean droplet size was observed between the diffusion-weighted MRI-based and the laser deflection measurements, showing the best performance with complex-based spatial averaging with neighborhood-regularized residual minimization processing (R2 /P: 0.971/0.014). In the human adipose-tissue samples, complex-based spatial averaging with neighborhood-regularized residual minimization processing showed a significant correlation (R2 /P: 0.531/0.017) compared with histology. CONCLUSION: The proposed acquisition and parameter-estimation methodology was able to probe restricted diffusion effects in lipid droplets. The methodology was validated using phantoms, and its feasibility in measuring an apparent lipid droplet size was demonstrated ex vivo in white adipose tissue.

Physiological variation of the vertebral bone marrow water T2 relaxation time.

The aim of this study was to investigate physiological variations of the water T2 relaxation time in vertebral bone marrow with respect to age, body mass index (BMI), sex and proton density fat fraction (PDFF) based on single-voxel magnetic resonance spectroscopy (MRS) at 3 T. Multi-TE single-voxel STEAM MRS data of a single lumbar vertebra (L4 or L5) from 260 subjects (160/100 female/male, age: 0.7/37.1/77.7 years, BMI: 13.6/26.2/44.5 kg/m2 [min./median/max.]) with no history of vertebral bone marrow pathologies were retrospectively included. All data were processed using a joint series T2-constrained time domain-based water-fat model. Water T2 and PDFF data were analyzed using (a) Pearson's correlation r and (b) multiple linear regression without interactions of the independent variables. Min./median/max. water T2 and PDFF were 11.2/21.1/42.5 ms and 4.0%/36.8%/82.0%, respectively. Pearson's correlation coefficients were significant (P < .05) for water T2 versus age (r = -0.429/-0.210 female/male) and for water T2 versus PDFF (r = -0.580/-0.546 female/male) for females and males, respectively. Females showed significant higher water T2 values compared with males (P < .001). Multiple linear regression for water T2 without interactions revealed a R2 = 0.407 with PDFF (P < .001) and sex (P < .001) as significant predictors. The current study suggests that under physiological conditions vertebral bone marrow water T2 is negatively correlated with age and PDFF and shows significant differences between females and males. The observed systematic trends are of relevance for the evaluation of T2 values and T2-weighted bone marrow parameters. Further research on the exact mechanisms and drivers of the observed water T2 behavior is required.

MRI-Based Quantitative Osteoporosis Imaging at the Spine and Femur.

Osteoporosis is a systemic skeletal disease with a high prevalence worldwide, characterized by low bone mass and microarchitectural deterioration, predisposing an individual to fragility fractures. Dual-energy X-ray absorptiometry (DXA) has been the clinical reference standard for diagnosing osteoporosis and for assessing fracture risk for decades. However, other imaging modalities are of increasing importance to investigate the etiology, treatment, and fracture risk. The purpose of this work is to review the available literature on quantitative magnetic resonance imaging (MRI) methods and related findings in osteoporosis at the spine and proximal femur as the clinically most important fracture sites. Trabecular bone microstructure analysis at the proximal femur based on high-resolution MRI allows for a better prediction of osteoporotic fracture risk than DXA-based bone mineral density (BMD) alone. In the 1990s, T2 * mapping was shown to correlate with the density and orientation of the trabecular bone. Recently, quantitative susceptibility mapping (QSM), which overcomes some of the limitations of T2 * mapping, has been applied for trabecular bone quantifications at the spine, whereas ultrashort echo time (UTE) imaging provides valuable surrogate markers of cortical bone quantity and quality. Magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) enable the quantitative assessment of the nonmineralized bone compartment through extraction of the bone marrow fat fraction (BMFF). Furthermore, CSE-MRI allows for the differentiation of osteoporotic vs. pathologic fractures, which is of high clinical relevance. Lastly, advanced postprocessing and image analysis tools, particularly considering statistical parametric mapping and region-specific BMFF distributions, have high potential to further improve MRI-based fracture risk assessments at the spine and hip. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 2.

Reduction of vibration-induced signal loss by matching mechanical vibrational states: Application in high b-value diffusion-weighted MRS.

PURPOSE: Diffusion encoding gradients are known to yield vibrations of the typical clinical MR scanner hardware with a frequency of 20 to 30 Hz, which may lead to signal loss in diffusion-weighted MR measurements. This work proposes to mitigate vibration-induced signal loss by introducing a vibration-matching gradient (VMG) to match vibrational states during the 2 diffusion gradient pulses. THEORY AND METHODS: A theoretical description of displacements induced by gradient switching was introduced and modeled by a 2-mass-spring-damper system. An additional preceding VMG mimicking timing and properties of the diffusion encoding gradients was added to a high b-value diffusion-weighted MR spectroscopy sequence. Laser interferometry was employed to measure 3D displacements of a phantom surface. Lipid ADC was assessed in water-fat phantoms and in vivo in the tibial bone marrow of 3 volunteers. RESULTS: The modeling and the laser interferometer measurements revealed that the displacement curves are more similar during the 2 diffusion gradients with the VMG compared to the standard sequence, resulting in less signal loss of the diffusion-weighted signal. Phantom results showed lipid ADC overestimation up to 119% with the standard sequence and an error of 5.5% with the VMG. An 18% to 35% lower coefficient of variation was obtained for in vivo lipid ADC measurement when employing the VMG. CONCLUSION: The application of the VMG reduces the signal loss introduced by hardware vibrations in a high b-value diffusion-weighted MRS sequence in phantoms and in vivo. Reference measurements based on laser interferometry and mechanical modelling confirmed the findings.

Water T2 Mapping in Fatty Infiltrated Thigh Muscles of Patients With Neuromuscular Diseases Using a T2 -Prepared 3D Turbo Spin Echo With SPAIR.

BACKGROUND: Muscle water T2 (T2w ) has been proposed as a biomarker to monitor disease activity and therapy effectiveness in patients with neuromuscular diseases (NMD). Multi-echo spin-echo (MESE) is known to be affected by fatty infiltration. A T2 -prepared 3D turbo spin echo (TSE) is an alternative method for T2 mapping, but has been only applied in healthy muscles. PURPOSE: To examine the performance of T2 -prepared 3D TSE in combination with spectral adiabatic inversion recovery (SPAIR) in measuring T2w in fatty infiltrated muscles based on simulations and in vivo measurements in thigh muscles of patients with NMD. STUDY TYPE: Prospective. SUBJECTS: One healthy volunteer, 34 NMD patients. FIELD STRENGTH/SEQUENCE: T2 -prepared stimulated echo acquisition mode (STEAM) magnetic resonance spectroscopy (MRS), SPAIR STEAM MRS, and SPAIR T2 -prepared STEAM MRS were performed in the subcutaneous fat of a healthy volunteer's thigh. T2 mapping based on SPAIR 2D MESE and SPAIR T2 -prepared 3D TSE was performed in the NMD patients' thigh region. Multi-TE STEAM MRS was performed for measuring a reference T2w at different thigh locations. ASSESSMENT: The behavior of the fat spectrum in the SPAIR T2 -prepared 3D TSE was simulated using Bloch simulations. The in vivo T2 results of the imaging methods were compared to the in vivo T2w MRS results. STATISTICAL TESTS: Pearson correlation coefficient with slope and intercept, relative error. RESULTS: The simulated T2 for the SPAIR T2 -prepared 3D TSE sequence remained constant within a relative error of not more than 4% up to a fat fraction of 80%. In vivo T2 values of SPAIR T2 -prepared 3D TSE were in good agreement with the T2w values of STEAM MRS (R = 0.86; slope = 1.12; intercept = -1.41 ms). In vivo T2 values of SPAIR 2D MESE showed large deviations from the T2w values of STEAM MRS (R = 0.14; slope = 0.32; intercept = 38.83 ms). DATA CONCLUSION: The proposed SPAIR T2 -prepared 3D TSE shows reduced sensitivity to fatty infiltration for T2w mapping in the thigh muscles of NMD patients. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1727-1736.

On the sensitivity of quantitative susceptibility mapping for measuring trabecular bone density.

PURPOSE: To develop a methodological framework to simultaneously measure R2* and magnetic susceptibility in trabecularized yellow bone marrow and to investigate the sensitivity of Quantitative Susceptibility Mapping (QSM) for measuring trabecular bone density using a non-UTE multi-gradient echo sequence. METHODS: The ankle of 16 healthy volunteers and two patients was scanned using a time-interleaved multi-gradient-echo (TIMGRE) sequence. After field mapping based on water-fat separation methods and background field removal based on the Laplacian boundary value method, three different QSM dipole inversion schemes were implemented. Mean susceptibility values in regions of different trabecular bone density in the calcaneus were compared to the corresponding values in the R2* maps, bone volume to total volume ratios (BV/TV) estimated from high resolution imaging (in 14 subjects), and CT attenuation (in two subjects). In addition, numerical simulations were performed in a simplified trabecular bone model of randomly positioned spherical bone inclusions to verify and compare the scaling of R2* and susceptibility with BV/TV. RESULTS: Differences in calcaneus trabecularization were well depicted in susceptibility maps, in good agreement with high-resolution MR and CT images. Simulations and in vivo scans showed a linear relationship of measured susceptibility with BV/TV and R2* . The ankle in vivo results showed a strong linear correlation between susceptibility and R2* (R2  = 0.88, p < 0.001) with a slope and intercept of -0.004 and 0.2 ppm, respectively. CONCLUSIONS: A method for multi-paramteric mapping, including R2* -mapping and QSM was developed for measuring trabecularized yellow bone marrow, showing good sensitivity of QSM for measuring trabecular bone density.

Measuring large lipid droplet sizes by probing restricted lipid diffusion effects with diffusion-weighted MRS at 3T.

PURPOSE: The in vivo probing of restricted diffusion effects in large lipid droplets on a clinical MR scanner remains a major challenge due to the need for high b-values and long diffusion times. This work proposes a methodology to probe mean lipid droplet sizes using diffusion-weighted MRS (DW-MRS) at 3T. METHODS: An analytical expression for restricted diffusion was used. Simulations were performed to evaluate the noise performance and the influence of particle size distribution. To validate the method, oil-in-water emulsions were prepared and examined using DW-MRS, laser deflection and light microscopy. The tibia bone marrow was scanned in volunteers to test the method repeatability and characterize microstructural differences at different locations. RESULTS: The simulations showed accurate and precise droplet size estimation when a sufficient SNR is reached with minor dependence on the size distribution. In phantoms, a good correlation between the measured droplet sizes by DW-MRS and by laser deflection (R2 = 0.98; P = 0.01) and microscopy (R2 = 0.99; P < 0.01) measurements was obtained. A mean coefficient of variation of 11.5 % was found for the lipid droplet diameter in vivo. The average diameter was smaller at a proximal (50.1 ± 7.3 µm) compared with a distal tibia location (61.1 ± 6.8 µm) (P < 0.01). CONCLUSION: The presented methods were able to probe restricted diffusion effects in lipid droplets using DW-MRS and to estimate lipid droplet size. The methodology was validated using phantoms and the in vivo feasibility in bone marrow was shown based on a good repeatability and findings in agreement with literature.

Decreased water T2 in fatty infiltrated skeletal muscles of patients with neuromuscular diseases.

Quantitative imaging techniques are emerging in the field of magnetic resonance imaging of neuromuscular diseases (NMD). T2 of water (T2w ) is considered an important imaging marker to assess acute and chronic alterations of the muscle fibers, being generally interpreted as an indicator for "disease activity" in the muscle tissue. To validate the accuracy and robustness of quantitative imaging methods, 1 H magnetic resonance spectroscopy (MRS) can be used as a gold standard. The purpose of the present work was to investigate T2w of remaining muscle tissue in regions of higher proton density fat fraction (PDFF) in 40 patients with defined NMD using multi-TE single-voxel 1 H MRS. Patients underwent MR measurements on a 3 T system to perform a multi-TE single-voxel stimulated echo acquisition method (STEAM) MRS (TE = 11/15/20/25(/35) ms) in regions of healthy, edematous and fatty thigh muscle tissue. Muscle regions for MRS were selected based on T2 -weighted water and fat images of a two-echo 2D Dixon TSE. MRS results were confined to regions with qualitatively defined remaining muscle tissue without edema and high fat content, based on visual grading of the imaging data. The results showed decreased T2w values with increasing PDFF with R2  = 0.45 (p < 10-3 ) (linear fit) and with R2  = 0.51 (exponential fit). The observed dependence of T2w on PDFF should be considered when using T2w as a marker in NMD imaging and when performing single-voxel MRS for T2w in regions enclosing edematous, nonedematous and fatty infiltrated muscle tissue.

Differentiating supraclavicular from gluteal adipose tissue based on simultaneous PDFF and T2 * mapping using a 20-echo gradient-echo acquisition.

BACKGROUND: Adipose tissue (AT) can be classified into white and brown/beige subtypes. Chemical shift encoding-based water-fat MRI-techniques allowing simultaneous mapping of proton density fat fraction (PDFF) and T2 * result in a lower PDFF and a shorter T2 * in brown compared with white AT. However, AT T2 * values vary widely in the literature and are primarily based on 6-echo data. Increasing the number of echoes in a multiecho gradient-echo acquisition is expected to increase the precision of AT T2 * mapping. PURPOSE: 1) To mitigate issues of current T2 *-measurement techniques through experimental design, and 2) to investigate gluteal and supraclavicular AT T2 * and PDFF and their relationship using a 20-echo gradient-echo acquisition. STUDY TYPE: Prospective. SUBJECTS: Twenty-one healthy subjects. FIELD STRENGTH/SEQUENCE ASSESSMENT: First, a ground truth signal evolution was simulated from a single-T2 * water-fat model. Second, a time-interleaved 20-echo gradient-echo sequence with monopolar gradients of neck and abdomen/pelvis at 3 T was performed in vivo to determine supraclavicular and gluteal PDFF and T2 *. Complex-based water-fat separation was performed for the first 6 echoes and the full 20 echoes. AT depots were segmented. STATISTICAL TESTS: Mann-Whitney test, Wilcoxon signed-rank test and simple linear regression analysis. RESULTS: Both PDFF and T2 * differed significantly between supraclavicular and gluteal AT with 6 and 20 echoes (PDFF: P < 0.0001 each, T2 *: P = 0.03 / P < 0.0001 for 6/20 echoes). 6-echo T2 * demonstrated higher standard deviations and broader ranges than 20-echo T2 *. Regression analyses revealed a strong relationship between PDFF and T2 * values per AT compartment (R2 = 0.63 supraclavicular, R2 = 0.86 gluteal, P < 0.0001 each). DATA CONCLUSION: The present findings suggest that an increase in the number of sampled echoes beyond 6 does not affect AT PDFF quantification, whereas AT T2 * is considerably affected. Thus, a 20-echo gradient-echo acquisition enables a multiparametric analysis of both AT PDFF and T2 * and may therefore improve MR-based differentiation between white and brown fat. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:424-434.

Vertebral bone marrow fat fraction changes in postmenopausal women with breast cancer receiving combined aromatase inhibitor and bisphosphonate therapy.

BACKGROUND: Quantification of vertebral bone marrow (VBM) water-fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period. METHODS: Twenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP). All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject. All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4. RESULTS: Baseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05). CONCLUSIONS: Over a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.