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Cardiac motion causes unpredictable signal loss in respiratory-triggered diffusion-weighted magnetic resonance imaging (DWI) of the liver, especially inside the left lobe. The left liver lobe may thus be frequently neglected in the clinical evaluation of liver DWI. In this work, a data-driven algorithm that relies on the statistics of the signal in the left liver lobe to mitigate the motion-induced signal loss is presented. The proposed data-driven algorithm utilizes the exclusion of severely corrupted images with subsequent spatially dependent image scaling based on a signal-loss model to correctly combine the multi-average diffusion-weighted images. The signal in the left liver lobe is restored and the liver signal is more homogeneous after applying the proposed algorithm. Furthermore, overestimation of the apparent diffusion coefficient (ADC) in the left liver lobe is reduced. The proposed algorithm can therefore contribute to reduce the motion-induced bias in DWI of the liver and help to increase the diagnostic value of DWI in the left liver lobe.

Abstract Background Tension-type headache (TTH) is the most prevalent primary headache disorder. Neck pain is commonly associated with primary headaches and the trigemino-cervical complex (TCC) refers to the convergence of trigeminal and cervical afferents onto neurons of the brainstem, thus conceptualizes the emergence of headache in relation to neck pain. However, no objective biomarkers exist for the myofascial involvement in primary headaches. This study aimed to investigate the involvement of the trapezius muscles in primary headache disorders by quantitative magnetic resonance imaging (MRI), and to explore associations between muscle T2 values and headache frequency and neck pain. Methods This cohort study prospectively enrolled fifty participants (41 females, age range 20–31 years): 16 subjects with TTH only (TTH-), 12 with mixed-type TTH plus migraine (TTH+), and 22 healthy controls (HC). The participants completed fat-suppressed T2‐prepared three-dimensional turbo spin-echo MRI, a headache diary (over 30 days prior to MRI), manual palpation (two weeks before MRI), and evaluation of neck pain (on the day of MRI). The bilateral trapezius muscles were manually segmented, followed by muscle T2 extraction. Associations between muscle T2 and the presence of neck pain as well as the number of days with headache (considering the 30 days prior to imaging using the headache calendar) were analyzed using regression models (adjusting for age, sex, and body mass index). Results The TTH+ group demonstrated the highest muscle T2 values (right side: 31.4 ± 1.2 ms, left side: 31.4 ± 0.8 ms) as compared to the TTH- group or HC group (p

Purpose: Multi-echo Stack-of-stars (SoS) radial k-space trajectories with golden angle ordering are becoming popular for free-breathing abdominal Dixon imaging and proton density fat fraction (PDFF) mapping. Gradient chain imperfections including eddy currents and system delays are known to affect the image quality of radial imaging and to confound the estimation of PDFF mapping. This work proposes a retrospective trajectory correction method based on a simple gradient modulation transfer function (GMTF) measurement to predict and correct gradient chain induced k-space trajectory errors.Methods: The GMTF was measured using the standard hardware of a 3 Tesla scanner on a phantom using the thin slice method and was applied to a 3D radial SoS Dixon imaging sequence. The impact of the GMTF-based correction on image reconstruction and PDFF quantification was investigated using numerical simulations and validated on experimental phantom data as well as on in vivo leg and liver data of healthy volunteers.Results: Correcting the k-space trajectories with the measured GMTF during image reconstruction reduced PDFF quantification errors for phantom and in vivo acquisitions. A Bland-Altman comparison of the measured PDFF phantom and reference data confirmed that the GMTF correction narrowed down the limits of agreement (LoA) from 1.3% ± 8.1% (uncorrected) to 1.9% ± 5.4% (GMTF-corrected) over the full PDFF range (0%–100%) and from −0.26% ± 2.8% (uncorrected) to 0.12% ± 1.5% (GMTF-corrected) within the 0%–50% PDFF range. Liver PDFF estimation was improved by reducing the standard deviation of the mean liver PDFF and the bias of the mean liver PDFF for all subjects.Conclusion: The proposed GMTF-based k-space trajectory correction is a fast alternative method for avoiding PDFF quantitation errors caused by gradient-system induced k-space trajectory errors in 3D radial multi-echo gradient-echo acquisitions.

Measurement(s) Vertebral Body • Intervertebral Disc Technology Type(s) Magnetic Resonance Imaging

Abstract Background To evaluate the diagnostic value of MR-derived CT-like images and simulated radiographs compared with conventional radiographs in patients with suspected shoulder pathology. Methods 3 T MRI of the shoulder including a 3D T1-weighted gradient echo sequence was performed in 25 patients (mean age 52.4 ± 18 years, 13 women) with suspected shoulder pathology. Subsequently a cone-beam forward projection algorithm was used to obtain intensity-inverted CT-like images and simulated radiographs. Two radiologists evaluated the simulated images separately and independently using the conventional radiographs as the standard of reference, including measurements of the image quality, acromiohumeral distance, critical shoulder angle, degenerative joint changes and the acromial type. Additionally, the CT-like MR images were evaluated for glenoid defects, subcortical cysts and calcifications. Agreement between the MR-derived simulated radiographs and conventional radiographs was calculated using Cohen’s Kappa. Results Measurements on simulated radiographs and conventional radiographs overall showed a substantial to almost perfect inter- and intra-rater agreement (κ = 0.69–1.00 and κ = 0.65–0.85, respectively). Image quality of the simulated radiographs was rated good to excellent (1.6 ± 0.7 and 1.8 ± 0.6, respectively) by the radiologists. A substantial agreement was found regarding diagnostically relevant features, assessed on Y- and anteroposterior projections (κ = 0.84 and κ = 0.69 for the measurement of the CSA; κ = 0.95 and κ = 0.60 for the measurement of the AHD; κ = 0.77 and κ = 0.77 for grading of the Samilson-Prieto classification; κ = 0.83 and κ = 0.67 for the grading of the Bigliani classification, respectively). Conclusion In this proof-of-concept study, clinically relevant features of the shoulder joint were assessed reliably using MR-derived CT-like images and simulated radiographs with an image quality equivalent to conventional radiographs. MR-derived CT-like images and simulated radiographs may provide useful diagnostic information while reducing the amount of radiation exposure.

Abstract Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities—that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-d-glucose (18FDG) PET and dual-energy X-ray absorptiometry—shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.

BackgroundQuantitative 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.MethodsIn 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.ResultsPrior 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).ConclusionsIn 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.

PurposeOsteoporosis 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 MethodsSeven 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.ResultsMedian 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).ConclusionPDFF 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.

Summary: 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.

Purpose: Brown adipose tissue (BAT) plays a potential role in energy and glucose metabolism in humans. Thyroid hormones (TH) are main regulators of BAT development and function. However, it remains unknown how the magnetic resonance (MR)-based proton density fat fraction (PDFF) of supraclavicular adipose tissue used as a surrogate marker for BAT presence relates to TH. Therefore, the purpose of this analysis was to investigate the relationship between supraclavicular PDFF and serum levels of TH. Methods: In total, 96 adult volunteers from a large cross-sectional study who underwent additional MR examination of the neck and pelvis were included in this analysis. Segmented PDFF maps of the supraclavicular and gluteal subcutaneous adipose tissue were generated. Delta PDFF was calculated as the difference between gluteal and supraclavicular PDFF and grouped as high (≥12%) or low (

Abstract Background We investigated the composition of the gluteal (gluteus maximus, medius, and minimus) and quadriceps (rectus femoris, vastus lateralis, medialis, and intermedius) muscle groups and its associations with femoral bone marrow using chemical shift encoding-based water-fat magnetic resonance imaging (CSE-MRI) to improve our understanding of muscle-bone interaction. Methods Thirty healthy volunteers (15 males, aged 30.5 ± 4.9 years [mean ± standard deviation]; 15 females, aged 29.9 ± 7.1 years) were recruited. A six-echo three-dimensional spoiled gradient-echo sequence was used for 3-T CSE-MRI at the thigh and hip region. The proton density fat fraction (PDFF) of the gluteal and quadriceps muscle groups as well as of the femoral head, neck, and greater trochanter bone marrow were extracted and averaged over both sides. Results PDFF values of all analysed bone marrow compartments were significantly higher in men than in women (p ≤ 0.047). PDFF values of the analysed muscles showed no significant difference between men and women (p ≥ 0.707). After adjusting for age and body mass index, moderate significant correlations of PDFF values were observed between the gluteal and quadriceps muscle groups (r = 0.670) and between femoral subregions (from r = 0.613 to r = 0.655). Regarding muscle-bone interactions, only the PDFF of the quadriceps muscle and greater trochanter bone marrow showed a significant correlation (r = 0.375). Conclusions The composition of the muscle and bone marrow compartments at the thigh and hip region in young, healthy subjects seems to be quite distinct, without evidence for a strong muscle-bone interaction.

BackgroundThe difference of proton density fat fraction (PDFF) between supraclavicular and gluteal adipose tissue might indicate the presence of brown adipose tissue (BAT). Aim of this cross-sectional study was to investigate the association between PDFF over the supraclavicular fat region as a proxy of BAT proportion and resting metabolic rate (RMR). In addition, the association between the single nucleotide polymorphism (SNP) rs1421085 at the fat mass and obesity associated (FTO) gene locus and both PDFF and RMR was investigated.MethodsAnthropometric, clinical, and lifestyle data from 92 healthy adults (66.3% females, mean age: 36.2 ± 13.0 years, mean body mass index: 24.9 ± 5.4 kg/m2) were included in the analysis. The RMR was measured by indirect calorimetry. The magnetic resonance imaging (MRI) was used for the measurement of visceral and subcutaneous adipose tissue (VAT, SAT) volumes and for the measurement of adipose tissue PDFF.ResultsMean RMR of the whole group was 1 474.8 ± 242.2 kcal. Genotype data was available for 90 participants. After adjustment for age, sex, weight change and fat-free mass (FFM), no association was found between supraclavicular PDFF (p = 0.346) and gluteal PDFF (p = 0.252), respectively, and RMR, whereas statistically significant evidence for a negative association between delta PDFF (difference between gluteal PDFF and supraclavicular PDFF) and RMR (p = 0.027) was obtained. No statistically significant evidence was observed for per FTO risk allele change in RMR, gluteal and supraclavicular PDFF maps or volumes of VAT and SAT.ConclusionsSupraclavicular PDFF as a surrogate marker of BAT presence is not a determinant of RMR under basal conditions. In the present study, the FTO rs1421085 variant is not associated with either RMR or PDFF. Further studies are needed to elucidate the effect of BAT on RMR.

PurposeOsteoporosis 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 MethodsTwenty-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.ResultsPatients with osteoporotic vertebral fractures showed significantly lower integral and trabecular vBMD when compared to patients without fractures (p

Abstract 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.

Abstract Background Assessment of the thigh muscle fat composition using magnetic resonance imaging (MRI) can provide surrogate markers in subjects suffering from various musculoskeletal disorders including knee osteoarthritis or neuromuscular diseases. However, little is known about the relationship with muscle strength. Therefore, we investigated the associations of thigh muscle fat with isometric strength measurements. Methods Twenty healthy subjects (10 females; median age 27 years, range 22–41 years) underwent chemical shift encoding-based water-fat MRI, followed by bilateral extraction of the proton density fat fraction (PDFF) and calculation of relative cross-sectional area (relCSA) of quadriceps and ischiocrural muscles. Relative maximum voluntary isometric contraction (relMVIC) in knee extension and flexion was measured with a rotational dynamometer. Correlations between PDFF, relCSA, and relMVIC were evaluated, and multivariate regression was applied to identify significant predictors of muscle strength. Results Significant correlations between the PDFF and relMVIC were observed for quadriceps and ischiocrural muscles bilaterally (p = 0.001 to 0.049). PDFF, but not relCSA, was a statistically significant (p = 0.001 to 0.049) predictor of relMVIC in multivariate regression models, except for left-sided relMVIC in extension. In this case, PDFF (p = 0.005) and relCSA (p = 0.015) of quadriceps muscles significantly contributed to the statistical model with R 2 adj = 0.548. Conclusion Chemical shift encoding-based water-fat MRI could detect changes in muscle composition by quantifying muscular fat that correlates well with both extensor and flexor relMVIC of the thigh. Our results help to initiate early, individualised treatments to maintain or improve muscle function in subjects who do not or not yet show pathological fatty muscle infiltration.

Abstract 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.

Abstract Background Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. Methods Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. Results The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. Conclusions Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Chemical shift encoding-based water–fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) has been used for non-invasive assessment of regional body fat distributions. More recently, texture analysis (TA) has been proposed to reveal even more detailed information about the vertebral or muscular composition beyond PDFF. The aim of this study was to investigate associations between vertebral bone marrow and paraspinal muscle texture features derived from CSE-MRI-based PDFF maps in a cohort of healthy subjects. In this study, 44 healthy subjects (13 males, 55 ± 30 years; 31 females, 39 ± 17 years) underwent 3T MRI including a six-echo three-dimensional (3D) spoiled gradient echo sequence used for CSE-MRI at the lumbar spine and the paraspinal musculature. The erector spinae muscles (ES), the psoas muscles (PS), and the vertebral bodies L1-4 (LS) were manually segmented. Mean PDFF values and texture features were extracted for each compartment. Features were compared between males and females using logistic regression analysis adjusted for age and body mass index (BMI). All texture features of ES except for Sum Average were significantly (p < 0.05) different between men and women. The three global texture features (Variance, Skewness, Kurtosis) for PS as well as LS showed a significant difference between male and female subjects (p < 0.05). Mean PDFF measured in PS and ES was significantly higher in females, but no difference was found for the vertebral bone marrow’s PDFF. Partial correlation analysis between the texture features of the spine and the paraspinal muscles revealed a highly significant correlation for Variance(global) (r = 0.61 for ES, r = 0.62 for PS; p < 0.001 respectively). Texture analysis using PDFF maps based on CSE-MRI revealed differences between healthy male and female subjects. Global texture features in the lumbar vertebral bone marrow allowed for differentiation between men and women, when the overall PDFF was not significantly different, indicating that PDFF maps may contain detailed and subtle textural information beyond fat fraction. The observed significant correlation of Variance(global) suggests a metabolic interrelationship between vertebral bone marrow and the paraspinal muscles.

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.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) methods can non-invasively assess brown adipose tissue (BAT) structure and function. Recently, MRI and MRS have been proposed as a means to differentiate BAT from white adipose tissue (WAT) and to extract morphological and functional information on BAT inaccessible by other means. Specifically, proton MR (1H) techniques, such as proton density fat fraction mapping, diffusion imaging, and intermolecular multiple quantum coherence imaging, have been employed to access BAT microstructure; MR thermometry, relaxometry, and MRI and MRS with 31P, 2H, 13C, and 129Xe have shown to provide complementary information on BAT function. The purpose of the present review is to provide a comprehensive overview of MR imaging and spectroscopy techniques used to detect BAT in rodents and in humans. The present work discusses common challenges of current methods and provides an outlook on possible future directions of using MRI and MRS in BAT studies.

The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical or clinical BMA researchers, searched the literature for articles investigating BMA and discussed the results during personal and telephone conferences. According to the consensus opinion, both based on the review of the literature and on expert opinion, we describe existing methodologies and discuss the challenges and future directions for (1) histomorphometry of bone marrow adipocytes, (2) ex vivo BMA imaging, (3) in vivo BMA imaging, (4) cell isolation, culture, differentiation and in vitro modulation of primary bone marrow adipocytes and bone marrow stromal cell precursors, (5) lineage tracing and in vivo BMA modulation, and (6) BMA biobanking. We identify as accepted standards in BMA research: manual histomorphometry and osmium tetroxide 3D contrast-enhanced μCT for ex vivo quantification, specific MRI sequences (WFI and H-MRS) for in vivo studies, and RT-qPCR with a minimal four gene panel or lipid-based assays for in vitro quantification of bone marrow adipogenesis. Emerging techniques are described which may soon come to complement or substitute these gold standards. Known confounding factors and minimal reporting standards are presented, and their use is encouraged to facilitate comparison across studies. In conclusion, specific BMA methodologies have been developed. However, important challenges remain. In particular, we advocate for the harmonization of methodologies, the precise reporting of known confounding factors, and the identification of methods to modulate BMA independently from other tissues. Wider use of existing animal models with impaired BMA production (e.g., Pfrt−/−, KitW/W−v) and development of specific BMA deletion models would be highly desirable for this purpose.

Abstract Proton-density fat fraction (PDFF) of the paraspinal muscles, derived from chemical shift encoding-based water-fat magnetic resonance imaging, has emerged as an important surrogate biomarker in individuals with intervertebral disc disease, osteoporosis, sarcopenia and neuromuscular disorders. However, quantification of paraspinal muscle PDFF is currently limited in clinical routine due to the required time-consuming manual segmentation procedure. The present study aimed to develop an automatic segmentation algorithm of the lumbar paraspinal muscles based on water-fat sequences and compare the performance of this algorithm to ground truth data based on manual segmentation. The algorithm comprised an average shape model, a dual feature model, associating each surface point with a fat and water image appearance feature, and a detection model. Right and left psoas, quadratus lumborum and erector spinae muscles were automatically segmented. Dice coefficients averaged over all six muscle compartments amounted to 0.83 (range 0.75–0.90).

Central fat accumulation is a significant determinant of cardio-metabolic health risk, known to differ between ethnically distinct human populations. Despite evidence for preferential central adiposity in Asian populations, the proportional distribution between the subcutaneous and visceral compartments in Chinese postmenopausal women has not been thoroughly investigated. For this analysis, volumetrically quantified subcutaneous and visceral adipose tissue (SAT, VAT) in the pelvic and abdominal regions of postmenopausal Asian (Chinese-Singaporean) and Caucasian (German) women matched for age and Body Mass Index (BMI) was undertaken, to examine such differences between the two groups. Volumes were calculated from segmentations of magnetic resonance imaging datasets of the abdomen and pelvis. Despite SAT, VAT, and the corresponding total adipose tissue (TAT) being similar between the groups, VAT/SAT and VAT/TAT were higher in the Asian group (by 24.5% and 18.2%, respectively, each p = 0.02). Further, VAT/SAT and VAT/TAT were positively correlated with BMI in the Caucasian group only (p = 0.02 and p = 0.01, respectively). We concluded that VAT is proportionally higher in the non-obese Asian women, compared to the Caucasian women of matched age and BMI. This conclusion is in agreement with existing literature showing higher abdominal adiposity in Asian populations. Additionally, in the Asian group, BMI did not correlate with visceral adiposity on a significant level. Further analysis is required to examine the extent to which this increased VAT may impact cardio-metabolic health. There is, however, a need to emphasize healthy lifestyle behaviors in non-obese post-menopausal women of Chinese ancestry.

In this study, the associations of cervical and lumbar paraspinal musculature based on a texture analysis of proton density fat fraction (PDFF) maps were investigated to identify gender- and anatomical location-specific structural patterns. Seventy-nine volunteers (25 men, 54 women) participated in the present study (mean age ± standard deviation: men: 43.7 ± 24.6 years; women: 37.1 ± 14.0 years). Using manual segmentations of the PDFF maps, texture analysis was performed and texture features were extracted. A significant difference in the mean PDFF between men and women was observed in the erector spinae muscle (p < 0.0001), whereas the mean PDFF did not significantly differ in the cervical musculature and the psoas muscle (p > 0.05 each). Among others, Variance(global) and Kurtosis(global) showed significantly higher values in men than in women in all included muscle groups (p < 0.001). Not only the mean PDFF values (p < 0.001) but also Variance(global) (p < 0.001), Energy (p < 0.001), Entropy (p = 0.01), Homogeneity (p < 0.001), and Correlation (p = 0.037) differed significantly between the three muscle compartments. The cervical and lumbar paraspinal musculature composition seems to be gender-specific and has anatomical location-specific structural patterns.

(1) Background and Purpose: The skeletal muscles of patients suffering from neuromuscular diseases (NMD) are affected by atrophy, hypertrophy, fatty infiltration, and edematous changes. Magnetic resonance imaging (MRI) is an important tool for diagnosis and monitoring. Concerning fatty infiltration, T1-weighted or T2-weighted DIXON turbo spin echo (TSE) sequences enable a qualitative assessment of muscle involvement. To achieve higher comparability, semi-quantitative grading scales, such as the four-point Mercuri scale, are commonly applied. However, the evaluation remains investigator-dependent. Therefore, effort is being invested to develop quantitative MRI techniques for determination of imaging markers such as the proton density fat fraction (PDFF). The present work aims to assess the diagnostic value of PDFF in correlation to Mercuri grading and clinically determined muscle strength in patients with myotonic dystrophy type 2 (DM2), limb girdle muscular dystrophy type 2A (LGMD2A), and adult Pompe disease. (2) Methods: T2-weighted two-dimensional (2D) DIXON TSE and chemical shift encoding-based water-fat MRI were acquired in 13 patients (DM2: n = 5; LGMD2A: n = 5; Pompe disease: n = 3). Nine different thigh muscles were rated in all patients according to the Mercuri grading and segmented to extract PDFF values. Muscle strength was assessed according to the British Medical Research Council (BMRC) scale. For correlation analyses between Mercuri grading, muscle strength, and PDFF, the Spearman correlation coefficient (rs) was computed. (3) Results: Mean PDFF values ranged from 7% to 37% in adults with Pompe disease and DM2 and up to 79% in LGMD2A patients. In all three groups, a strong correlation of the Mercuri grading and PDFF values was observed for almost all muscles (rs > 0.70, p < 0.05). PDFF values correlated significantly to muscle strength for muscle groups responsible for knee flexion (rs = −0.80, p < 0.01). (4) Conclusion: In the small, investigated patient cohort, PDFF offers similar diagnostic precision as the clinically established Mercuri grading. Based on these preliminary data, PDFF could be further considered as an MRI-based biomarker in the assessment of fatty infiltration of muscle tissue in NMD. Further studies with larger patient cohorts are needed to advance PDFF as an MRI-based biomarker in NMD, with advantages such as its greater dynamic range, enabling the assessment of subtler changes, the amplified objectivity, and the potential of direct correlation to muscle function for selected muscles.

Purpose: Based on conventional and quantitative magnetic resonance imaging (MRI), texture analysis (TA) has shown encouraging results as a biomarker for tissue structure. Chemical shift encoding-based water–fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) of thigh muscles has been associated with musculoskeletal, metabolic, and neuromuscular disorders and was demonstrated to predict muscle strength. The purpose of this study was to investigate PDFF-based TA of thigh muscles as a predictor of thigh muscle strength in comparison to mean PDFF. Methods: 30 healthy subjects (age = 30 ± 6 years; 15 females) underwent CSE-MRI of the lumbar spine at 3T, using a six-echo 3D spoiled gradient echo sequence. Quadriceps (EXT) and ischiocrural (FLEX) muscles were segmented to extract mean PDFF and texture features. Muscle flexion and extension strength were measured with an isokinetic dynamometer. Results: Of the eleven extracted texture features, Variance(global) showed the highest significant correlation with extension strength (p < 0.001, R2adj = 0.712), and Correlation showed the highest significant correlation with flexion strength (p = 0.016, R2adj = 0.658). Multivariate linear regression models identified Variance(global) and sex, but not PDFF, as significant predictors of extension strength (R2adj = 0.709; p < 0.001), while mean PDFF, sex, and BMI, but none of the texture features, were identified as significant predictors of flexion strength (R2adj = 0.674; p < 0.001). Conclusions: Prediction of quadriceps muscle strength can be improved beyond mean PDFF by means of TA, indicating the capability to quantify muscular fat infiltration patterns.

Texture analysis (TA) has shown promise as a surrogate marker for tissue structure, based on conventional and quantitative MRI sequences. Chemical-shift-encoding-based MRI (CSE-MRI)-derived proton density fat fraction (PDFF) of paraspinal muscles has been associated with various medical conditions including lumbar back pain (LBP) and neuromuscular diseases (NMD). Its application has been shown to improve the prediction of paraspinal muscle strength beyond muscle volume. Since mean PDFF values do not fully reflect muscle tissue structure, the purpose of our study was to investigate PDFF-based TA of paraspinal muscles as a predictor of muscle strength, as compared to mean PDFF. We performed 3T-MRI of the lumbar spine in 26 healthy subjects (age = 30 ± 6 years; 15 females) using a six-echo 3D spoiled gradient echo sequence for chemical-shift-encoding-based water–fat separation. Erector spinae (ES) and psoas (PS) muscles were segmented bilaterally from level L2–L5 to extract mean PDFF and texture features. Muscle flexion and extension strength was measured with an isokinetic dynamometer. Out of the eleven texture features extracted for each muscle, Kurtosis(global) of ES showed the highest significant correlation (r = 0.59, p = 0.001) with extension strength and Variance(global) of PS showed the highest significant correlation (r = 0.63, p = 0.001) with flexion strength. Using multivariate linear regression models, Kurtosis(global) of ES and BMI were identified as significant predictors of extension strength (R2adj = 0.42; p < 0.001), and Variance(global) and Skewness(global) of PS were identified as significant predictors of flexion strength (R2adj = 0.59; p = 0.001), while mean PDFF was not identified as a significant predictor. TA of CSE-MRI-based PDFF maps improves the prediction of paraspinal muscle strength beyond mean PDFF, potentially reflecting the ability to quantify the pattern of muscular fat infiltration. In the future, this may help to improve the pathophysiological understanding, diagnosis, monitoring and treatment evaluation of diseases with paraspinal muscle involvement, e.g., NMD and LBP.

Purpose: Advanced magnetic resonance imaging (MRI) methods enable non-invasive quantification of body fat situated in different compartments. At the level of the lumbar spine, the paraspinal musculature is the compartment spatially and functionally closely related to the vertebral column, and both vertebral bone marrow fat (BMF) and paraspinal musculature fat contents have independently shown to be altered in various metabolic and degenerative diseases. However, despite their close relationships, potential correlations between fat compositions of these compartments remain largely unclear.Materials and Methods: Thirty-nine female subjects (38.5% premenopausal women, 29.9 ± 7.1 years; 61.5% postmenopausal women, 63.2 ± 6.3 years) underwent MRI at 3T of the lumbar spine using axially- and sagittally-prescribed gradient echo sequences for chemical shift encoding-based water-fat separation. The erector spinae muscles and vertebral bodies of L1–L5 were segmented to determine the proton density fat fraction (PDFF) of the paraspinal and vertebral bone marrow compartments. Correlations were calculated between the PDFF of the paraspinal muscle and bone marrow compartments.Results: The average PDFF of the paraspinal muscle and bone marrow compartments were significantly lower in premenopausal women when compared to postmenopausal women (11.6 ± 2.9% vs. 24.6 ± 7.1% & 28.8 ± 8.3% vs. 47.2 ± 8.5%; p < 0.001 for both comparisons). In premenopausal women, no significant correlation was found between the PDFF of the erector spinae muscles and the PDFF of the bone marrow of lumbar vertebral bodies (p = 0.907). In contrast, a significant correlation was shown in postmenopausal women (r = 0.457, p = 0.025). Significance was preserved after inclusion of age and body mass index (BMI) as control variables (r = 0.472, p = 0.027).Conclusion: This study revealed significant correlations between the PDFF of paraspinal and vertebral bone marrow compartments in postmenopausal women. The PDFF of the paraspinal and vertebral bone marrow compartments and their correlations might potentially serve as biomarkers; however, future studies including more subjects are required to evaluate distinct clinical value and reliability. Future studies should also follow up our findings in patients suffering from metabolic and degenerative diseases to clarify how these correlations change in the course of such diseases.

After publication of this article [1], it is noticed it contained some errors in the Methods section.

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) 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.

Bone marrow adiposity has recently gained attention due to its association with bone loss pathophysiology. In this study, ten vertebrae were harvested from fresh human cadavers. Trabecular BMD and microstructure parameters were extracted from MDCT. Bone marrow fat fractions were determined using single-voxel MRS. Failure load (FL) values were assessed by destructive biomechanical testing. Significant correlations (P