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.

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.

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.

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.

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.

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.

Vertebral Bone Marrow Heterogeneity Using Texture Analysis of Chemical Shift Encoding-Based MRI: Variations in Age, Sex, and Anatomical Location.

Objective: Vertebral bone marrow composition has been extensively studied in the past and shown potential as imaging biomarker for osteoporosis, hematopoietic, and metabolic disorders. However, beyond quantitative assessment of bone marrow fat, little is known about its heterogeneity. Therefore, we investigated bone marrow heterogeneity of the lumbar spine using texture analysis of chemical-shift-encoding (CSE-MRI) based proton density fat fraction (PDFF) maps and its association with age, sex, and anatomical location. Methods: One hundred and fifty-six healthy subjects were scanned (age range: 20-29 years, 12/30 males/females; 30-39, 15/9; 40-49, 5/13; 50-59, 9/27; ≥60: 9/27). A sagittal 8-echo 3D spoiled-gradient-echo sequence at 3T was used for CSE-MRI-based water-fat separation at the lumbar spine. Manual segmentation of vertebral bodies L1-4 was performed. Mean PDFF and texture features (global: variance, skewness, kurtosis; second-order: energy, entropy, contrast, homogeneity, correlation, sum-average, variance, dissimilarity) were extracted at each vertebral level and compared between age groups, sex, and anatomical location. Results: Mean PDFF significantly increased from L1 to L4 (35.89 ± 11.66 to 39.52 ± 11.18%, p = 0.017) and with age (females: 27.19 ± 6.01 to 49.34 ± 7.75%, p < 0.001; males: 31.97 ± 7.96 to 41.83 ± 7.03 %, p = 0.025), but showed no difference between females and males after adjustment for age and BMI (37.13 ± 11.63 vs. 37.17 ± 8.67%; p = 0.199). Bone marrow heterogeneity assessed by texture analysis, in contrast to PDFF, was significantly higher in females compared to males after adjustment for age and BMI (namely contrast and dissimilarity; p < 0.031), demonstrated age-dependent differences, in particular in females (p < 0.05), but showed no statistically significant dependence on vertebral location. Conclusion: Vertebral bone marrow heterogeneity, assessed by texture analysis of PDFF maps, is primarily dependent on sex and age but not on anatomical location. Future studies are needed to investigate bone marrow heterogeneity with regard to aging and disease.

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.

Validation of diffuse reflectance spectroscopy with magnetic resonance imaging for accurate vertebral bone fat fraction quantification.

Safe and accurate placement of pedicle screws remains a critical step in open and minimally invasive spine surgery. The diffuse reflectance spectroscopy (DRS) technique may offer the possibility of intra-operative guidance for pedicle screw placement. Currently, Magnetic Resonance Imaging (MRI) is one of the most accurate techniques used to measure fat concentration in tissues. Therefore, the purpose of this study is to compare the accuracy of fat content measured invasively in vertebrae using DRS and validate it against the Proton density fat fraction (PDFF) derived via MRI. Chemical shift-encoding-based water-fat imaging of the spine was first performed on six cadavers. PDFF images were computed and manually segmented. 23 insertions using a custom-made screw probe with integrated optical fibers were then performed under cone beam computer tomography (CBCT). DR spectra were recorded at several positions along the trajectory as the optical screw probe was inserted turn by turn into the vertebral body. Fat fractions determined via DRS and MRI techniques were compared by spatially correlating the optical screw probe position within the vertebrae on CBCT images with respect to the PDFF images. The fat fraction determined by DRS was found to have a high correlation with those determined by MRI, with a Pearson coefficient of 0.950 (P< 0.001) as compared with PDFF measurements calculated from the MRI technique. Additionally, the two techniques were found to be comparable for fat fraction quantification within vertebral bodies (R2 = 0.905).

Comparison of regional bone marrow adiposity characteristics at the hip of underweight and weight-recovered women with anorexia nervosa using magnetic resonance spectroscopy.

Bone marrow adiposity (BMA) is an underestimated tissue, with properties that may alter bone strength especially in diseases that fragilize bone such as anorexia nervosa. In the present study, we investigated the regional characteristics of BMA at the hip of 40 underweight and 36 weight-recovered anorexic women, along with 10 healthy women, using magnetic resonance spectroscopy at multiple anatomical subregions (acetabulum, femoral neck, proximal femoral diaphysis and greater trochanter) to measure bone marrow fat fraction (BMFF) and apparent lipid unsaturation levels (aLUL). Correlations between BMFF, aLUL, body fat percentage (BF), and bone mineral density (BMD) at the femoral neck and total hip, both measured using dual-energy X-ray absorptiometry, were assessed in anorexic patients. Whereas BMFF was significantly higher and aLUL significantly lower at the femoral neck of underweight and weight-recovered patients compared to controls (BMFF: 90.1 ±â€¯6.7% and 90.3 ±â€¯7.5% respectively versus 81.3 ±â€¯8.1%; aLUL: 7.6 ±â€¯1.4% and 7.3 ±â€¯1.3% versus 9.2 ±â€¯1.5%), BMFF and aLUL were not significantly different between the 2 subgroups of patients. Besides, three noteworthy features were observed between BMA and the other measured parameters in anorexic patients. First, synergic alterations of BMA were observed at all sites, with an inverse relationship between BMFF and aLUL (ρ = -0.88). Second, bone mineral compartment and BMA were associated, as a negative correlation between total hip BMD and BMFF was observed at all sites except the greater trochanter (ρ = [-0.32;-0.29]), as well as a positive correlation with aLUL at all sites except the proximal femoral diaphysis (ρ = [0.25;0.37]). Finally, we found a positive correlation between BF and BMFF at the femoral neck (ρ = 0.35), and a negative correlation between BF and aLUL at this same subregion (ρ = -0.33), which suggest a complex relationship between BMA and BF. Overall, BMA possesses regional specificities which may impair bone health, even after weight recovering.

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.

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.

Anatomical Variation of Age-Related Changes in Vertebral Bone Marrow Composition Using Chemical Shift Encoding-Based Water-Fat Magnetic Resonance Imaging.

Assessment of vertebral bone marrow composition has been proposed as imaging biomarker for osteoporosis, hematopoietic, and metabolic disorders. We investigated the anatomical variation of age-related changes of vertebral proton density fat fraction (PDFF) using chemical shift encoding-based water-fat magnetic resonance imaging (MRI). 156 healthy subjects were recruited (age range 20-29 years: 12/30 males/females; 30-39: 15/9; 40-49: 4/14; 50-59: 9/27; 60-69: 5/19; 70-79: 4/8). An eight-echo 3D spoiled gradient-echo sequence at 3T MRI was used for chemical shift-encoding based water-fat separation at the lumbar spine. Vertebral bodies of L1-L4 were manually segmented to extract PDFF values at each vertebral level. PDFF averaged over L1-L4 was significantly (p < 0.05) higher in males than females in the twenties (32.0 ± 8.0 vs. 27.2 ± 6.0%) and thirties (35.3 ± 6.7 vs. 27.3 ± 6.2%). With increasing age, females showed an accelerated fatty conversion of the bone marrow compared to men with no significant (p > 0.05) mean PDFF differences in the forties (32.4 ± 8.4 vs. 34.5 ± 6.8%) and fifties (42.0 ± 6.1 vs. 40.5 ± 9.7%). The accelerated conversion process continued resulting in greater mean PDFF values in females than males in the sixties (40.2 ± 6.9 vs. 48.8 ± 7.7%; p = 0.033) and seventies (43.9 ± 7.6 vs. 50.5 ± 8.2%; p = 0.208), though the latter did not reach statistical significance. Relative age-related PDFF change from the twenties to the seventies increased from 16.7% (L1) to 51.4% (L4) in males and 76.8% (L1) to 85.7% (L4) in females. An accelerated fatty conversion of bone marrow was observed in females with increasing age particularly evident after menopause. Relative age-related PDFF changes showed an anatomical variation with most pronounced changes at lower lumbar vertebral levels in both sexes.