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.

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.

Bone Marrow Adiposity and Fragility Fractures in Postmenopausal Women: The ADIMOS Case-Control Study.

CONTEXT: Noninvasive assessment of proton density fat fraction (PDFF) by magnetic resonance imaging (MRI) may improve the prediction of fractures. OBJECTIVE: This work aimed to determine if an association exists between PDFF and fractures. METHODS: A case-control study was conducted at Lille University Hospital, Lille, France, with 2 groups of postmenopausal women: one with recent osteoporotic fractures, and the other with no fractures. Lumbar spine and proximal femur (femoral head, neck, and diaphysis) PDFF were determined using chemical shift-based water-fat separation MRI (WFI) and dual-energy x-ray absorptiometry scans of the lumbar spine and hip. Our primary objective was to determine the relationship between lumbar spine PDFF and osteoporotic fractures in postmenopausal women. Analysis of covariance was used to compare PDFF measurements between patient cases (overall and according to the type of fracture) and controls, after adjusting for age, Charlson comorbidity index (CCI) and BMD. RESULTS: In 199 participants, controls (n = 99) were significantly younger (P < .001) and had significantly higher BMD (P < 0.001 for all sites) than patient cases (n = 100). A total of 52 women with clinical vertebral fractures and 48 with nonvertebral fractures were included. When PDFFs in patient cases and controls were compared, after adjustment on age, CCI, and BMD, no statistically significant differences between the groups were found at the lumbar spine or proximal femur. When PDFFs in participants with clinical vertebral fractures (n = 52) and controls were compared, femoral neck PDFF and femoral diaphysis PDFF were detected to be lower in participants with clinical vertebral fractures than in controls (adjusted mean [SE] 79.3% [1.2] vs 83.0% [0.8]; P = 0.020, and 77.7% [1.4] vs 81.6% [0.9]; P = 0.029, respectively). CONCLUSION: No difference in lumbar spine PDFF was found between those with osteoporotic fractures and controls. However, imaging-based proximal femur PDFF may discriminate between postmenopausal women with and without clinical vertebral fractures, independently of age, CCI, and BMD.

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.

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.

Associations of incidental vertebral fractures and longitudinal changes of MR-based proton density fat fraction and T2* measurements of vertebral bone marrow.

Background: Quantitative magnetic resonance imaging (MRI) techniques such as chemical shift encoding-based water-fat separation techniques (CSE-MRI) are increasingly applied as noninvasive biomarkers to assess the biochemical composition of vertebrae. This study aims to investigate the longitudinal change of proton density fat fraction (PDFF) and T2* derived from CSE-MRI of the thoracolumbar vertebral bone marrow in patients that develop incidental vertebral compression fractures (VCFs), and whether PDFF and T2* enable the prediction of an incidental VCF. Methods: In this study we included 48 patients with CT-derived bone mineral density (BMD) measurements at baseline. Patients that presented an incidental VCF at follow up (N=12, mean age 70.5 ± 7.4 years, 5 female) were compared to controls without incidental VCF at follow up (N=36, mean age 71.1 ± 8.6 years, 15 females). All patients underwent 3T MRI, containing a significant part of the thoracolumbar spine (Th11-L4), at baseline, 6-month and 12 month follow up, including a gradient echo sequence for chemical shift encoding-based water-fat separation, from which PDFF and T2* maps were obtained. Associations between changes in PDFF, T2* and BMD measurements over 12 months and the group (incidental VCF vs. no VCF) were assessed using multivariable regression models. Mixed-effect regression models were used to test if there is a difference in the rate of change in PDFF, T2* and BMD between patients with and without incidental VCF. Results: Prior to the occurrence of an incidental VCF, PDFF in vertebrae increased in the VCF group (ΔPDFF=6.3 ± 3.1%) and was significantly higher than the change of PDFF in the group without VCF (ΔPDFF=2.1 ± 2.5%, P=0.03). There was no significant change in T2* (ΔT2*=1.7 ± 1.1ms vs. ΔT2*=1.1 ± 1.3ms, P=0.31) and BMD (ΔBMD=-1.2 ± 11.3mg/cm3 vs. ΔBMD=-11.4 ± 24.1mg/cm3, P= 0.37) between the two groups over 12 months. At baseline, no significant differences were detected in the average PDFF, T2* and BMD of all measured vertebrae (Th11-L4) between the VCF group and the group without VCF (P=0.66, P=0.35 and P= 0.21, respectively). When assessing the differences in rates of change, there was a significant change in slope for PDFF (2.32 per 6 months, 95% confidence interval (CI) 0.31-4.32; P=0.03) but not for T2* (0.02 per 6 months, CI -0.98-0.95; P=0.90) or BMD (-4.84 per 6 months, CI -23.4-13.7; P=0.60). Conclusions: In our study population, the average change of PDFF over 12 months is significantly higher in patients that develop incidental fractures at 12-month follow up compared to patients without incidental VCF, while T2* and BMD show no significant changes prior to the occurrence of the incidental vertebral fractures. Therefore, a longitudinal increase in bone marrow PDFF may be predictive for vertebral compression fractures.

The Predictive Value of Early Postoperative MRI-Based Bone Marrow Parameters for Mid-Term Outcome after MACI with Autologous Bone Grafting at the Knee.

OBJECTIVE: The aim of this study was to longitudinally determine the prognostic value of early postoperative quantitative 3T-MRI (magnetic resonance imaging) parameters of subchondral bone marrow for 2-year clinical and MRI outcome after matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) at the knee. DESIGN: Consecutive subjects who received MACI with ABG for treatment of focal osteochondral defects received MRI follow-up 3, 6, 12, and 24 months postoperatively. Quantitative MRI included bone marrow edema-like lesion (BMEL) volume measurements and single-voxel magnetic resonance spectroscopy (MRS; n = 9) of the subchondral bone marrow. At 2-year follow-up, morphological MRI outcome included MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. Clinical outcomes were assessed using Lysholm scores. RESULTS: Among a total of 18 subjects (mean age: 28.7 ± 8.4 years, n = 14 males) with defects at the medial or lateral (n = 15 and n = 3, respectively) condyle, mean BMEL volume decreased from 4.9 cm3 at 3 months to 2.0 cm3 at 2-year follow-up (P = 0.040). MRS-based bone marrow water T2 showed a decrease from 20.7 ms at 1-year follow-up to 16.8 ms at 2-year follow-up (P = 0.040). Higher BMEL volume at 6 months correlated with lower 2-year Lysholm (R = -0.616, P = 0.015) and MOCART 2.0 scores (R = -0.567, P = 0.027). Larger early postoperative BMEL volumes at 3 months (R = -0.850, P = 0.007) and 6 months (R = -0.811, P = 0.008) correlated with lower MRS-based unsaturated lipid fractions at 2-year follow-up. Furthermore, patients with early postoperative bony defects showed worse MOCART 2.0 (P = 0.044) and Lysholm scores (P = 0.017) after 24 months. CONCLUSION: Low subchondral BMEL volume and optimal restoration of the subchondral bone at early postoperative time points predict better 2-year clinical and MRI outcomes after MACI with ABG.

Finite Element Analysis of Osteoporotic and Osteoblastic Vertebrae and Its Association With the Proton Density Fat Fraction From Chemical Shift Encoding-Based Water-Fat MRI - A Preliminary Study.

Purpose: Osteoporosis is prevalent and entails alterations of vertebral bone and marrow. Yet, the spine is also a common site of metastatic spread. Parameters that can be non-invasively measured and could capture these alterations are the volumetric bone mineral density (vBMD), proton density fat fraction (PDFF) as an estimate of relative fat content, and failure displacement and load from finite element analysis (FEA) for assessment of bone strength. This study's purpose was to investigate if osteoporotic and osteoblastic metastatic changes in lumbar vertebrae can be differentiated based on the abovementioned parameters (vBMD, PDFF, and measures from FEA), and how these parameters correlate with each other. Materials and Methods: Seven patients (3 females, median age: 77.5 years) who received 3-Tesla magnetic resonance imaging (MRI) and multi-detector computed tomography (CT) of the lumbar spine and were diagnosed with either osteoporosis (4 patients) or diffuse osteoblastic metastases (3 patients) were included. Chemical shift encoding-based water-fat MRI (CSE-MRI) was used to extract the PDFF, while vBMD was extracted after automated vertebral body segmentation using CT. Segmentation masks were used for FEA-based failure displacement and failure load calculations. Failure displacement, failure load, and PDFF were compared between patients with osteoporotic vertebrae versus patients with osteoblastic metastases, considering non-fractured vertebrae (L1-L4). Associations between those parameters were assessed using Spearman correlation. Results: Median vBMD was 59.3 mg/cm3 in osteoporotic patients. Median PDFF was lower in the metastatic compared to the osteoporotic patients (11.9% vs. 43.8%, p=0.032). Median failure displacement and failure load were significantly higher in metastatic compared to osteoporotic patients (0.874 mm vs. 0.348 mm, 29,589 N vs. 3,095 N, p=0.034 each). A strong correlation was noted between PDFF and failure displacement (rho -0.679, p=0.094). A very strong correlation was noted between PDFF and failure load (rho -0.893, p=0.007). Conclusion: PDFF as well as failure displacement and load allowed to distinguish osteoporotic from diffuse osteoblastic vertebrae. Our findings further show strong associations between PDFF and failure displacement and load, thus may indicate complimentary pathophysiological associations derived from two non-invasive techniques (CSE-MRI and CT) that inherently measure different properties of vertebral bone and marrow.

Hierarchical Multi-Resolution Graph-Cuts for Water-Fat-Silicone Separation in Breast MRI.

Water-fat separation is a non-linear non-convex parameter estimation problem in magnetic resonance imaging typically solved using spatial constraints. However, there is still limited knowledge on how to separate in vivo three chemical species in the presence of magnetic field inhomogeneities. The proposed method uses multiple graph-cuts in a hierarchical multi-resolution framework to perform robust chemical species separation in the breast for subjects with and without silicone implants. Experimental results show that the proposed method can decrease the computational time for water-fat separation and perform accurate water-fat-silicone separation with only a limited number of acquired echo images at 3 T. The silicone-separated images have an improved spatial resolution and image contrast compared to conventional scans used for regular monitoring of the silicone implant's integrity.

Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue.

BACKGROUND: The adipocyte-hypertrophy associated remodeling of fat cell function is considered causal for the development of metabolic disorders. A better understanding of transcriptome and fatty acid (FA) related alterations with adipocyte hypertrophy combined with less-invasive strategies for the detection of the latter can help to increase the prognostic and diagnostic value of adipocyte size and FA composition as markers for metabolic disease. METHODS: To clarify adipocyte-hypertrophy associated transcriptomic alterations, fat cell size was related to RNA-Seq data from white adipose tissue and size-separated adipocytes. The relationship between adipocyte size and adipose tissue FA composition as measured by GC-MS was investigated. MR spectroscopy (MRS) methods for clinical scanning were developed to characterize adipocyte size and FA composition in a fast and non-invasive manner. FINDINGS: With enlarged adipocyte size, substantial transcriptomic alterations of genes involved in mitochondrial function and FA metabolism were observed. Investigations of these two mechanisms revealed a reciprocal relationship between adipocyte size and estimated thermogenic adipocyte content as well as depot-specific correlations of adipocyte size and FA composition. MRS on a clinical scanner was suitable for the in-parallel assessment of adipose morphology and FA composition. INTERPRETATION: The current study provides a comprehensive overview of the adipocyte-hypertrophy associated transcriptomic and FA landscape in both subcutaneous and visceral adipose tissue. MRS represents a promising technique to translate the observed mechanistic, structural and functional changes in WAT with adipocyte hypertrophy into a clinical context for an improved phenotyping of WAT in the context of metabolic diseases. FUNDING: Competence network for obesity (FKZ 42201GI1128), ERC (No 677661, ProFatMRI; No 875488, FatVirtualBiopsy), Else Kröner-Fresenius-Foundation.

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.

Vertebral bone marrow T2* mapping using chemical shift encoding-based water-fat separation in the quantitative analysis of lumbar osteoporosis and osteoporotic fractures.

BACKGROUND: Chemical shift encoding-based water-fat separation techniques have been used for fat quantification [proton density fat fraction (PDFF)], but they also enable the assessment of bone marrow T2*, which has previously been reported to be a potential biomarker for osteoporosis and may give insight into the cause of vertebral fractures (i.e., osteoporotic vs. traumatic) and the microstructure of the bone when applied to vertebral bone marrow. METHODS: The 32 patients (78.1% with low-energy osteopenic/osteoporotic fractures, mean age 72.3±9.8 years, 76% women; 21.9% with high-energy traumatic fractures, 47.3±12.8 years, no women) were frequency-matched for age and sex to subjects without vertebral fractures (n=20). All study patients underwent 3T-MRI of the lumbar spine including sagittally acquired spoiled gradient echo sequences for chemical shift encoding-based water-fat separation, from which T2* values were obtained. Volumetric trabecular bone mineral density (BMD) and trabecular bone parameters describing the three-dimensional structural integrity of trabecular bone were derived from quantitative CT. Associations between T2* measurements, fracture status and trabecular bone parameters were assessed using multivariable linear regression models. RESULTS: Mean T2* values of non fractured vertebrae in all patients showed a significant correlation with BMD (r=-0.65, P<0.001), trabecular number (TbN) (r=-0.56, P<0.001) and trabecular spacing (TbSp) (r=0.61, P<0.001); patients with low-energy osteoporotic vertebral fractures showed significantly higher mean T2* values than those with traumatic fractures (13.6±4.3 vs. 8.4±2.2 ms, P=0.01) as well as a significantly lower TbN (0.69±0.08 vs. 0.93±0.03 mm-1, P<0.01) and a significantly larger trabecular spacing (1.06±0.16 vs. 0.56±0.08 mm, P<0.01). Mean T2* values of osteoporotic patients with and without vertebral fracture showed no significant difference (13.5±3.4 vs. 15.6±3.5 ms, P=0.40). When comparing the mean T2* of the fractured vertebrae, no significant difference could be detected between low-energy osteoporotic fractures and high-energy traumatic fractures (12.6±5.4 vs. 8.1±2.4 ms, P=0.10). CONCLUSIONS: T2* mapping of vertebral bone marrow using using chemical shift encoding-based water-fat separation allows for assessing osteoporosis as well as the trabecular microstructure and enables a radiation-free differentiation between patients with low-energy osteoporotic and high-energy traumatic vertebral fractures, suggesting its potential as a biomarker for bone fragility.

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.

Quantitative 3-T Magnetic Resonance Imaging After Matrix-Associated Autologous Chondrocyte Implantation With Autologous Bone Grafting of the Knee: The Importance of Subchondral Bone Parameters.

BACKGROUND: Matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) is an effective surgical treatment for osteochondral defects. Quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as noninvasive biomarkers to assess the biochemical composition of cartilage repair tissue. PURPOSE: To evaluate the association of quantitative MRI parameters of cartilage repair tissue and subchondral bone marrow with magnetic resonance morphologic and clinical outcomes after MACI with ABG of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Qualitative and quantitative 3 T MRI of the knee was performed in 21 patients (16 male) at 2.5 years after MACI with ABG at the medial (18/21) or lateral (3/21) femoral condyle for the treatment of osteochondral defects. Morphologic MRI sequences were assessed using MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. T2 relaxation time measurements for the assessment of cartilage repair tissue (CRT2) were obtained. Single-voxel magnetic resonance spectroscopy was performed in underlying subchondral bone marrow (BM) and at both central femoral condyles. The presence of pain and Tegner scores were noted. Statistical analyses included Student t tests, correlation analyses, and multivariate regression models. RESULTS: The mean defect size was 4.9 ± 1.9 cm2. At a follow-up of 2.5 ± 0.3 years, 9 of 21 patients were asymptomatic. Perfect defect filling was achieved in 66.7% (14/21) of patients. MOCART 2.0 scores (74.1 ± 18.4) did not indicate pain (68.3 ± 19.0 [pain] vs 81.7 ± 15.4 [no pain]; P = .102). However, knee pain was present in 85.7% (6/7) of patients with deep bony defects (odds ratio, 8.0; P = .078). Relative CRT2 was higher in hypertrophic cartilage repair tissue than in repair tissue with normal filling (1.54 ± 0.42 vs 1.13 ± 0.21, respectively; P = .022). The underlying BM edema-like lesion (BMEL) volume was larger in patients with underfilling compared with patients with perfect defect filling (1.87 ± 1.32 vs 0.31 ± 0.51 cm3, respectively; P = .002). Patients with severe pain showed a higher BMEL volume (1.2 ± 1.3 vs 0.2 ± 0.4 cm3, respectively; P = .046) and had a higher BM water fraction (26.0% ± 12.3% vs 8.6% ± 8.1%, respectively; P = .026) than did patients without pain. CONCLUSION: Qualitative and quantitative MRI parameters including the presence of subchondral defects, CRT2, BMEL volume, and BM water fraction were correlated with cartilage repair tissue quality and clinical symptoms. Therefore, the integrity of subchondral bone was associated with outcomes after osteochondral transplantation.

Texture Analysis Using CT and Chemical Shift Encoding-Based Water-Fat MRI Can Improve Differentiation Between Patients With and Without Osteoporotic Vertebral Fractures.

Purpose: Osteoporosis is a highly prevalent skeletal disease that frequently entails vertebral fractures. Areal bone mineral density (BMD) derived from dual-energy X-ray absorptiometry (DXA) is the reference standard, but has well-known limitations. Texture analysis can provide surrogate markers of tissue microstructure based on computed tomography (CT) or magnetic resonance imaging (MRI) data of the spine, thus potentially improving fracture risk estimation beyond areal BMD. However, it is largely unknown whether MRI-derived texture analysis can predict volumetric BMD (vBMD), or whether a model incorporating texture analysis based on CT and MRI may be capable of differentiating between patients with and without osteoporotic vertebral fractures. Materials and Methods: Twenty-six patients (15 females, median age: 73 years, 11 patients showing at least one osteoporotic vertebral fracture) who had CT and 3-Tesla chemical shift encoding-based water-fat MRI (CSE-MRI) available were analyzed. In total, 171 vertebral bodies of the thoracolumbar spine were segmented using an automatic convolutional neural network (CNN)-based framework, followed by extraction of integral and trabecular vBMD using CT data. For CSE-MRI, manual segmentation of vertebral bodies and consecutive extraction of the mean proton density fat fraction (PDFF) and T2* was performed. First-order, second-order, and higher-order texture features were derived from texture analysis using CT and CSE-MRI data. Stepwise multivariate linear regression models were computed using integral vBMD and fracture status as dependent variables. Results: Patients with osteoporotic vertebral fractures showed significantly lower integral and trabecular vBMD when compared to patients without fractures (p<0.001). For the model with integral vBMD as the dependent variable, T2* combined with three PDFF-based texture features explained 40% of the variance (adjusted R2[Ra2] = 0.40; p<0.001). Furthermore, regarding the differentiation between patients with and without osteoporotic vertebral fractures, a model including texture features from CT and CSE-MRI data showed better performance than a model based on integral vBMD and PDFF only ( Ra2 = 0.47 vs. Ra2  = 0.81; included texture features in the final model: integral vBMD, CT_Short-run_emphasis, CT_Varianceglobal, and PDFF_Variance). Conclusion: Using texture analysis for spine CT and CSE-MRI can facilitate the differentiation between patients with and without osteoporotic vertebral fractures, implicating that future fracture prediction in osteoporosis may be improved.

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.

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.

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.