Magnetic Resonance Assessment of Bone Quality in Metabolic Bone Diseases.

Metabolic bone diseases (MBDs) are a diverse group of diseases, affecting the mass or structure of bones and leading to reduced bone quality. Parameters representing different aspects of bone health can be obtained from various magnetic resonance imaging (MRI) methods such as proton MR spectroscopy, as well as chemical shift encoding-based water-fat imaging, that have been frequently applied to study bone marrow in particular. Furthermore, T2* mapping and high-resolution trabecular bone imaging have been implemented to study bone microstructure. In addition, quantitative susceptibility mapping and ultrashort echo time imaging are used for trabecular and cortical bone assessment. This review offers an overview of technical aspects, as well as major clinical applications and derived main findings, for MRI-based assessment of bone quality in MBDs. It focuses on osteoporosis as the most common MBD.

Differentiation of benign and malignant vertebral fractures using a convolutional neural network to extract CT-based texture features.

PURPOSE: To assess the diagnostic performance of three-dimensional (3D) CT-based texture features (TFs) using a convolutional neural network (CNN)-based framework to differentiate benign (osteoporotic) and malignant vertebral fractures (VFs). METHODS: A total of 409 patients who underwent routine thoracolumbar spine CT at two institutions were included. VFs were categorized as benign or malignant using either biopsy or imaging follow-up of at least three months as standard of reference. Automated detection, labelling, and segmentation of the vertebrae were performed using a CNN-based framework ( https://anduin.bonescreen.de ). Eight TFs were extracted: Varianceglobal, Skewnessglobal, energy, entropy, short-run emphasis (SRE), long-run emphasis (LRE), run-length non-uniformity (RLN), and run percentage (RP). Multivariate regression models adjusted for age and sex were used to compare TFs between benign and malignant VFs. RESULTS: Skewnessglobal showed a significant difference between the two groups when analyzing fractured vertebrae from T1 to L6 (benign fracture group: 0.70 [0.64-0.76]; malignant fracture group: 0.59 [0.56-0.63]; and p = 0.017), suggesting a higher skewness in benign VFs compared to malignant VFs. CONCLUSION: Three-dimensional CT-based global TF skewness assessed using a CNN-based framework showed significant difference between benign and malignant thoracolumbar VFs and may therefore contribute to the clinical diagnostic work-up of patients with VFs.

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.

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.

Effect of MRI acquisition acceleration via compressed sensing and parallel imaging on brain volumetry.

OBJECTIVES: To investigate the effect of compressed SENSE (CS), an acceleration technique combining parallel imaging and compressed sensing, on potential bias and precision of brain volumetry and evaluate it in the context of normative brain volumetry. MATERIALS AND METHODS: In total, 171 scans from scan-rescan experiments on three healthy subjects were analyzed. Each subject received 3D-T1-weighted brain MRI scans at increasing degrees of acceleration (CS-factor = 1/4/8/12/16/20/32). Single-scan acquisition times ranged from 00:41 min (CS-factor = 32) to 21:52 min (CS-factor = 1). Brain segmentation and volumetry was performed using two different software tools: md.brain, a proprietary software based on voxel-based morphometry, and FreeSurfer, an open-source software based on surface-based morphometry. Four sub-volumes were analyzed: brain parenchyma (BP), total gray matter, total white matter, and cerebrospinal fluid (CSF). Coefficient of variation (CoV) of the repeated measurements as a measure of intra-subject reliability was calculated. Intraclass correlation coefficient (ICC) with regard to increasing CS-factor was calculated as another measure of reliability. Noise-to-contrast ratio as a measure of image quality was calculated for each dataset to analyze the association between acceleration factor, noise and volumetric brain measurements. RESULTS: For all sub-volumes, there is a systematic bias proportional to the CS-factor which is dependent on the utilized software and subvolume. Measured volumes deviated significantly from the reference standard (CS-factor = 1), e.g. ranging from 1 to 13% for BP. The CS-induced systematic bias is driven by increased image noise. Except for CSF, reliability of brain volumetry remains high, demonstrated by low CoV (< 1% for CS-factor up to 20) and good to excellent ICC for CS-factor up to 12. CONCLUSION: CS-acceleration has a systematic biasing effect on volumetric brain measurements.

Normative brain volume reports may improve differential diagnosis of dementing neurodegenerative diseases in clinical practice.

OBJECTIVES: Normative brain volume reports (NBVRs) are becoming more and more available for the workup of dementia patients in clinical routine. However, it is yet unknown how this information can be used in the radiological decision-making process. The present study investigates the diagnostic value of NBVRs for detection and differential diagnosis of distinct regional brain atrophy in several dementing neurodegenerative disorders. METHODS: NBVRs were obtained for 81 consecutive patients with distinct dementing neurodegenerative diseases and 13 healthy controls (HC). Forty Alzheimer's disease (AD; 18 with dementia, 22 with mild cognitive impairment (MCI), 11 posterior cortical atrophy (PCA)), 20 frontotemporal dementia (FTD), and ten semantic dementia (SD) cases were analyzed, and reports were tested qualitatively for the representation of atrophy patterns. Gold standard diagnoses were based on the patients' clinical course, FDG-PET imaging, and/or cerebrospinal fluid (CSF) biomarkers following established diagnostic criteria. Diagnostic accuracy of pattern representations was calculated. RESULTS: NBVRs improved the correct identification of patients vs. healthy controls based on structural MRI for rater 1 (p < 0.001) whereas the amount of correct classifications was rather unchanged for rater 2. Correct differential diagnosis of dementing neurodegenerative disorders was significantly improved for both rater 1 (p = 0.001) and rater 2 (p = 0.022). Furthermore, interrater reliability was improved from moderate to excellent for both detection and differential diagnosis of neurodegenerative diseases (κ = 0.556/0.894 and κ = 0.403/0.850, respectively). CONCLUSION: NBVRs deliver valuable and observer-independent information, which can improve differential diagnosis of neurodegenerative diseases. KEY POINTS: • Normative brain volume reports increase detection of neurodegenerative atrophy patterns compared to visual reading alone. • Differential diagnosis of regionally distinct atrophy patterns is improved. • Agreement between radiologists is significantly improved from moderate to excellent when using normative brain volume reports.

Paraspinal Muscle DTI Metrics Predict Muscle Strength.

BACKGROUND: The paraspinal muscles play an important role in the onset and progression of lower back pain. It would be of clinical interest to identify imaging biomarkers of the paraspinal musculature that are related to muscle function and strength. Diffusion tensor imaging (DTI) enables the microstructural examination of muscle tissue and its pathological changes. PURPOSE: To investigate associations of DTI parameters of the lumbar paraspinal muscles with isometric strength measurements in healthy volunteers. STUDY TYPE: Prospective. SUBJECTS: Twenty-one healthy subjects (12 male, 9 female; age = 30.1 ± 5.6 years; body mass index [BMI] = 27.5 ± 2.6 kg/m2 ) were recruited. FIELD STRENGTH/SEQUENCE: 3 T/single-shot echo planar imaging (ss-EPI) DTI in 24 directions; six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water-fat separation. ASSESSMENT: Paraspinal muscles at the lumbar spine were examined. Erector spinae muscles were segmented bilaterally; cross-sectional area (CSA), proton density fat fraction (PDFF), and DTI parameters were calculated. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer and the ratio of extension to flexion strength (E/F) calculated. STATISTICAL TESTS: Pearson correlation coefficients; multivariate regression models. RESULTS: Significant positive correlations were found between the ratio of extension to flexion (E/F) strength and mean diffusivity (MD) (P = 0.019), RD (P = 0.02) and the eigenvalues (λ1: P = 0.026, λ2: P = 0.033, λ3: P = 0.014). In multivariate regression models λ3 of the erector spinae muscle λ3 and gender remained statistically significant predictors of E/F (R2adj = 0.42, P = 0.003). DATA CONCLUSION: DTI allowed the identification of muscle microstructure differences related to back muscle function that were not reflected by CSA and PDFF. DTI may potentially track subtle changes of back muscle tissue composition. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:816-823.

Association of paraspinal muscle water-fat MRI-based measurements with isometric strength measurements.

OBJECTIVES: Chemical shift encoding-based water-fat MRI derived proton density fat fraction (PDFF) of the paraspinal muscles has been emerging as a surrogate marker in subjects with sarcopenia, lower back pain, injuries and neuromuscular disorders. The present study investigates the performance of paraspinal muscle PDFF and cross-sectional area (CSA) in predicting isometric muscle strength. METHODS: Twenty-six healthy subjects (57.7% women; age: 30 ± 6 years) underwent 3T axial MRI of the lumbar spine using a six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water-fat separation. Erector spinae and psoas muscles were segmented bilaterally from L2 level to L5 level to determine CSA and PDFF. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer. RESULTS: Significant correlations between CSA and muscle strength measurements were observed for erector spinae muscle CSA (r = 0.40; p = 0.044) and psoas muscle CSA (r = 0.61; p = 0.001) with relative flexion strength. Erector spinae muscle PDFF correlated significantly with relative muscle strength (extension: r = -0.51; p = 0.008; flexion: r = -0.54; p = 0.005). Erector spinae muscle PDFF, but not CSA, remained a statistically significant (p < 0.05) predictor of relative extensor strength in multivariate regression models (R2adj = 0.34; p = 0.002). CONCLUSIONS: PDFF measurements improved the prediction of paraspinal muscle strength beyond CSA. Therefore, chemical shift encoding-based water-fat MRI may be used to detect subtle changes in the paraspinal muscle composition. KEY POINTS: • We investigated the association of paraspinal muscle fat fraction based on chemical shift encoding-based water-fat MRI with isometric strength measurements in healthy subjects. • Erector spinae muscle PDFF correlated significantly with relative muscle strength. • PDFF measurements improved prediction of paraspinal muscle strength beyond CSA.

Lumbar muscle and vertebral bodies segmentation of chemical shift encoding-based water-fat MRI: the reference database MyoSegmenTUM spine.

BACKGROUND: Magnetic resonance imaging (MRI) is the modality of choice for diagnosing and monitoring muscular tissue pathologies and bone marrow alterations in the context of lower back pain, neuromuscular diseases and osteoporosis. Chemical shift encoding-based water-fat MRI allows for reliable determination of proton density fat fraction (PDFF) of the muscle and bone marrow. Prior to quantitative data extraction, segmentation of the examined structures is needed. Performed manually, the segmentation process is time consuming and therefore limiting the clinical applicability. Thus, the development of automated segmentation algorithms is an ongoing research focus. CONSTRUCTION AND CONTENT: This database provides ground truth data which may help to develop and test automatic lumbar muscle and vertebra segmentation algorithms. Lumbar muscle groups and vertebral bodies (L1 to L5) were manually segmented in chemical shift encoding-based water-fat MRI and made publically available in the database MyoSegmenTUM. The database consists of water, fat and PDFF images with corresponding segmentation masks for lumbar muscle groups (right/left erector spinae and psoas muscles, respectively) and lumbar vertebral bodies 1-5 of 54 healthy Caucasian subjects. The database is freely accessible online at https://osf.io/3j54b/?view_only=f5089274d4a449cda2fef1d2df0ecc56 . CONCLUSION: A development and testing of segmentation algorithms based on this database may allow the use of quantitative MRI in clinical routine.

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.

Quantitative computed tomography in comparison with transpulmonary thermodilution for the estimation of pulmonary fluid status: a clinical study in critically ill patients.

Extravascular lung water (index) (EVLW(I)) can be estimated using transpulmonary thermodilution (TPTD). Computed tomography (CT) with quantitative analysis of lung tissue density has been proposed to quantify pulmonary edema. We compared variables of pulmonary fluid status assessed using quantitative CT and TPTD in critically ill patients. In 21 intensive care unit patients, we performed TPTD measurements directly before and after chest CT. Based on the density data of segmented CT images we calculated the tissue volume (TV), tissue volume index (TVI), and the mean weighted index of voxel aqueous density (VMWaq). CT-derived TV, TVI, and VMWaq did not predict TPTD-derived EVLWI values ≥ 14 mL/kg. There was a significant moderate positive correlation between VMWaq and mean EVLWI (EVLWI before and after CT) (r = 0.45, p = 0.042) and EVLWI after CT (r = 0.49, p = 0.025) but not EVLWI before CT (r = 0.38, p = 0.086). There was no significant correlation between TV and EVLW before CT, EVLW after CT, or mean EVLW. There was no significant correlation between TVI and EVLWI before CT, EVLWI after CT, or mean EVLWI. CT-derived variables did not predict elevated TPTD-derived EVLWI values. In unselected critically ill patients, variables of pulmonary fluid status assessed using quantitative CT cannot be used to predict EVLWI.

Epstein-Barr virus strain heterogeneity impairs human T-cell immunity.

The Epstein-Barr virus (EBV) establishes lifelong infections in > 90% of the human population. Although contained as asymptomatic infection by the immune system in most individuals, EBV is associated with the pathogenesis of approximately 1.5% of all cancers in humans. Some of these EBV-associated tumors have been successfully treated by the infusion of virus-specific T-cell lines. Recent sequence analyses of a large number of viral isolates suggested that distinct EBV strains have evolved in different parts of the world. Here, we assessed the impact of such sequence variations on EBV-specific T-cell immunity. With the exceptions of EBNA2 and the EBNA3 family of proteins, an overall low protein sequence disparity of about 1% was noted between Asian viral isolates, including the newly characterized M81 strain, and the prototypic EBV type 1 and type 2 strains. However, when T-cell epitopes including their flanking regions were compared, a substantial proportion was found to be polymorphic in different EBV strains. Importantly, CD4+ and CD8+ T-cell clones specific for viral epitopes from one strain often showed diminished recognition of the corresponding epitopes in other strains. In addition, T-cell recognition of a conserved epitope was affected by amino acid exchanges within the epitope flanking region. Moreover, the CD8+ T-cell response against polymorphic epitopes varied between donors and often ignored antigen variants. These results demonstrate that viral strain heterogeneity may impair antiviral T-cell immunity and suggest that immunotherapeutic approaches against EBV should preferably target broad sets of conserved epitopes including their flanking regions.

Quantitative MRI and spectroscopy of bone marrow.

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft-tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water-fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton-based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water-fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332-353.

ADC Quantification of the Vertebral Bone Marrow Water Component: Removing the Confounding Effect of Residual Fat.

PURPOSE: To remove the confounding effect of unsuppressed fat on the imaging-based apparent diffusion coefficient (ADC) of the vertebral bone marrow water component when using spectrally selective fat suppression and to compare and validate the proposed quantification strategy against diffusion-weighted magnetic resonance spectroscopy (DW-MRS). METHODS: Twelve subjects underwent diffusion-weighted imaging (DWI) and DW-MRS of the vertebral bone marrow. A theoretical model was developed to take into account and correct the effects of residual fat on ADC, incorporating additional measurements for proton density fat fraction (PDFF) and water T2 (T2w ). Uncorrected and corrected DWI-based ADC was compared with DW-MRS-based ADC using the Bland-Altman method. RESULTS: There was a systematic bias equal to 0.118 ± 0.116 × 10-3 mm2 /s between DWI and DW-MRS when no correction was performed. Taking into account measured PDFF and constant T2w reduced the bias to 0.006 ± 0.128 × 10-3 mm2 /s. Using the proposed approach with both individually measured PDFF and T2w reduced both the bias and the limits of agreement between DWI and DW-MRS (0.018 ± 0.065 × 10-3 mm2 /s). CONCLUSION: By taking into account the presence of residual fat in a modified signal model that incorporates additional individual measurements of PDFF and T2w , good agreement of imaging-based ADC with MRS-based ADC can be achieved in vertebral bone marrow. Magn Reson Med 78:1432-1441, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Association of Quadriceps Muscle Fat With Isometric Strength Measurements in Healthy Males Using Chemical Shift Encoding-Based Water-Fat Magnetic Resonance Imaging.

Magnetic resonance-based assessment of quadriceps muscle fat has been proposed as surrogate marker in sarcopenia, osteoarthritis, and neuromuscular disorders. We presently investigated the association of quadriceps muscle fat with isometric strength measurements in healthy males using chemical shift encoding-based water-fat magnetic resonance imaging. Intermuscular adipose tissue fraction and intramuscular proton density fat fraction correlated significantly (P < 0.05) with isometric strength (up to r = -0.83 and -0.87, respectively). Reproducibility of intermuscular adipose tissue fraction and intramuscular proton density fat fraction was 1.5% and 5.7%, respectively.

Modeling of T2* decay in vertebral bone marrow fat quantification.

Bone marrow fat fraction mapping using chemical shift encoding-based water-fat separation is becoming a useful tool in investigating the association between bone marrow adiposity and bone health and in assessing cancer treatment-induced bone marrow damage. Vertebral bone marrow is characterized by short T2* relaxation times, which are in general different for the water and fat components and can confound fat quantification. The purpose of the present study is to compare different approaches to T2* correction in chemical shift encoding-based water-fat imaging of vertebral bone marrow using single-voxel MRS as reference. Eight-echo gradient-echo imaging and single-voxel MRS measurements were made on the spine (L3-L5) of 25 healthy volunteers. Different approaches were evaluated for correction of T2* effects: (a) single-T2* correction, (b) dual-T2* correction, (c) T2' correction using the a priori-known T2 from the MRS at each vertebral body and (d) T2' correction using the a priori-known T2 equal to previously measured average values. Dual-T2* correction resulted in noisier imaging fat fraction maps than single-T2* correction or T2' correction using a priori-known T2. Linear regression analysis between imaging and MRS fat fraction showed a slope significantly different from 1 when using single-T2* correction (R(2) = 0.96) or dual-T2* correction (R(2) = 0.87). T2' correction using the a priori-known T2 resulted in a slope not significantly different from 1, an intercept significantly different from 0 (between 2.4% and 3%) and R(2) = 0.96. Therefore, a T2' correction using a priori-known T2 can remove the fat fraction bias induced by the difference in T2* between water and fat components without degrading noise performance in fat fraction mapping of vertebral bone marrow.

The need for T2 correction on MRS-based vertebral bone marrow fat quantification: implications for bone marrow fat fraction age dependence.

Vertebral bone marrow fat quantification using single-voxel MRS is confounded by overlapping water-fat peaks and the difference in T2 relaxation time between water and fat components. The purposes of the present study were: (i) to determine the proton density fat fraction (PDFF) of vertebral bone marrow using single-voxel multi-TE MRS, addressing these confounding effects; and (ii) to investigate the implications of these corrections with respect to the age dependence of the PDFF. Single-voxel MRS was performed in the L5 vertebral body of 86 subjects (54 women and 32 men). To reliably extract the water peak from the overlying fat peaks, the mean bone marrow fat spectrum was characterized based on the area of measurable fat peaks and an a priori knowledge of the chemical triglyceride structure. MRS measurements were performed at multiple TEs. The T2 -weighted fat fraction was calculated at each TE. In addition, a T2 correction was performed to obtain the PDFF and the T2 value of water (T2w ) was calculated. The implications of the T2 correction were investigated by studying the age dependence of the T2 -weighted fat fractions and the PDFF. Compared with the PDFF, all T2 -weighted fat fractions significantly overestimated the fat fraction. Compared with the age dependence of the PDFF, the age dependence of the T2 -weighted fat fraction showed an increased slope and intercept as TE increased for women and a strongly increased intercept as TE increased for men. For women, a negative association between the T2 value of bone marrow water and PDFF was found. Single-voxel MRS-based vertebral bone marrow fat quantification should be based on a multi-TE MRS measurement to minimize confounding effects on PDFF determination, and also to allow the simultaneous calculation of T2w , which might be considered as an additional parameter sensitive to the composition of the water compartment.

Assessment of whole spine vertebral bone marrow fat using chemical shift-encoding based water-fat MRI.

BACKGROUND: The assessment of bone marrow composition has recently gained significant attention due to its association with bone loss pathophysiology and cancer therapy-induced bone marrow damage. The purpose of our study was to investigate the anatomical variation of the vertebral bone marrow fat using chemical shift-encoding based water-fat MRI and to assess the repeatability of these measurements. METHODS: Chemical shift-encoding based water-fat MRI of the whole spine was performed in 28 young, healthy subjects (17 males, 11 females, 26 ± 4 years). Six subjects were scanned three times with repositioning to assess the repeatability of these measurements. Proton density fat fraction (PDFF) maps were computed and manually segmented to obtain PDFF of C3-L5. RESULTS: Mean PDFF of all subjects significantly increased from C3 to L5 (P < 0.05) with r = 0.88 (P < 0.05). PDFF averaged over C3-7, T1-6, T7-12, and L1-5 of males and females amounted to 31.7 ± 7.9% and 23.0 ± 7.8% (P = 0.002), 33.8 ± 6.8% and 24.6 ± 8.8% (P = 0.005), 33.8 ± 6.4% and 26.1 ± 6.4% (P = 0.023), and 38.8 ± 7.6% and 31.5 ± 12.4% (P = 0.063), respectively. The repeatability for PDFF measurements expressed as absolute precision error was 1.7% averaged over C3-L5. CONCLUSION: Whole spine vertebral bone marrow fat could be reproducibly assessed by using chemical shift-encoding based water-fat MRI and showed anatomical variations.