Chemical Shift Encoding-based Water-fat Separation Research Articles

Associations of gestational diabetes and proton density fat fraction of vertebral bone marrow and paraspinal musculature in premenopausal women.

Fat content in bones and muscles, quantified by magnetic resonance imaging (MRI) as a proton density fat fraction (PDFF) value, is an emerging non-invasive biomarker. PDFF has been proposed to indicate bone and metabolic health among postmenopausal women. Premenopausal women with a history of gestational diabetes (GDM) carry an increased risk of developing type 2 diabetes and an increased risk of fractures. However, no studies have investigated the associations between a history of GDM and PDFF of bone or of paraspinal musculature (PSM), composed of autochthonous muscle (AM) and psoas muscle, which are responsible for moving and stabilizing the spine. This study aims to investigate whether PDFF of vertebral bone marrow and of PSM are associated with a history of GDM in premenopausal women. A total of 37 women (mean age 36.3 ± 3.8 years) who were 6 to 15 months postpartum with (n=19) and without (n=18) a history of GDM underwent whole-body 3T MRI, including a chemical shift encoding-based water-fat separation. The PDFF maps were calculated for the vertebral bodies and PSM. The cross-sectional area (CSA) of PSM was obtained. Associations between a history of GDM and PDFF were assessed using multivariable linear and logistic regression models. The PDFF of the vertebral bodies was significantly higher in women with a history of GDM (GDM group) than in women without (thoracic: median 41.55 (interquartile range 32.21-49.48)% vs. 31.75 (30.03-34.97)%; p=0.02, lumbar: 47.84 (39.19-57.58)% vs. 36.93 (33.36-41.31)%; p=0.02). The results remained significant after adjustment for age and body mass index (BMI) (p=0.01-0.02). The receiver operating characteristic curves showed optimal thoracic andlumbar vertebral PDFF cutoffs at 38.10% and 44.18%, respectively, todifferentiate GDM (AUC 0.72 and 0.73, respectively, sensitivity 0.58, specificity 0.89). The PDFF of the AM was significantly higher in the GDM group (12.99 (12.18-15.90)% vs. 10.83 (9.39-14.71)%; p=0.04) without adjustments, while the CSA was similar between the groups (p=0.34). A history of GDM is significantly associated with a higher PDFF of the vertebral bone marrow, independent of age and BMI. This statistical association between GDM and increased PDFF highlights vertebral bone marrow PDFF as a potential biomarker for the assessment of bone health in premenopausal women at risk of diabetes.

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

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. 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. 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). 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.

Associations between Bone Mineral Density and Longitudinal Changes of Vertebral Bone Marrow and Paraspinal Muscle Composition Assessed Using MR-Based Proton Density Fat Fraction and T2* Maps in Patients with and without Osteoporosis.

Background: Proton-density fat fraction (PDFF) and T2* of the vertebrae, as well as the cross-sectional area (CSA) of the paraspinal musculature (PSM), have been suggested as biomarkers for bone fragility. The aim of this study was to longitudinally assess changes in PDFF, T2* and CSA of the PSM over 6 months in patients with and without osteoporosis. Methods: Opportunistic bone mineral density (BMD) measurements (BMD < 120 mg/cm3) were obtained from a CT acquired during the clinical routine work up in osteoporotic/osteopenic patients (n = 29, mean age 72.37 ± 10.12 years, 16 women). These patients were frequency-matched for age and sex to subjects with normal BMD values (n = 29). All study patients underwent 3T MR imaging at baseline and 6-month follow up, including spoiled gradient echo sequences for chemical shift encoding-based water-fat separation, from which T2* and PDFF values of the lumbar spine and the PSM were obtained. Moreover, the CSA of the PSM was assessed longitudinally. Changes in T2*, PDFF and CSA over 6 months were calculated for the vertebrae and PSM and associations with baseline BMD values were assessed. Results: The change in CSA of the PSM over 6 months was significantly lower in the osteoporotic/osteopenic group (−91.5 ± 311.7 mm2), compared to the non-osteoporotic group, in which the CSA increased (29.9 ± 164.0 mm2, p = 0.03). In a further analysis, patients with higher vertebral PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower vertebral PDFF at baseline (0.9 ± 1.6 ms vs. 0.0 ± 1.8 ms, p = 0.04). Moreover, patients with higher PSM PDFF at baseline showed a significantly stronger increase in vertebral T2*, compared to those patients with lower PSM PDFF at baseline (0.9 ± 2.0 ms vs. 0.0 ± 1.3 ms, p = 0.03). Conclusion: The PSM CSA decreased significantly longitudinally in patients with osteoporosis/osteopenia, compared to those without. Additionally, higher vertebral and PSM PDFF at baseline were associated with stronger changes in vertebral bone marrow T2*. Therefore, longitudinal PDFF and T2* mapping may be useful quantitative radiation-free tools for the assessment and prediction of muscle and bone health in patients with suspected osteoporosis/osteopenia.

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

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. 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. 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). 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.

Longitudinal changes on liver proton density fat fraction differ between liver segments

To study the spatial heterogeneity of liver fat fraction changes during a long-term lifestyle intervention study using magnetic resonance imaging (MRI). Thirty-two subjects underwent two MRI-scans in a span of one year. A chemical shift encoding-based water-fat separation method was applied to measure liver proton density fat fraction (PDFF) maps. The PDFF changes in the two liver lobes and the Couinaud segments were compared with the mean liver PDFF change. The slope of the relationship between mean liver PDFF changes and PDFF liver lobe changes was higher in the right compared to the left lobe (slopemean PDFF whole liver ~ mean PDFF right lobe =1.08, slopemean PDFF whole liver ~ mean PDFF left lobe =0.93, P<0.001). The highest slope of agreement between PDFF changes in each specific liver segment and mean liver PDFF changes was observed in segment VII (slope =1.12). The lowest slope of agreement between PDFF changes in each specific liver segment and mean liver PDFF changes was observed in segment I (slope =0.77). Larger PDFF changes in the right liver lobe were observed compared to PDFF changes in the left liver lobe (LLL) in subjects with both increasing and decreasing mean liver PDFF after one year. The results are in line with the existing literature reporting a heterogeneous spatial distribution of liver fat and highlight the need to spatially resolve liver fat fraction changes in longitudinal studies.

Age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content

This analysis investigated the age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content in order to detect fat distribution patterns and variations in healthy adults using proton density fat fraction (PDFF) measurements. A six-echo 3D spoiled gradient-echo sequence was used for chemical shift encoding-based water-fat separation at the sacral and lower lumbar region in 103 healthy volunteers. PDFF values of the sacrum, 5th lumbar vertebral body, the gluteal and paraspinal muscles were determined. Correlation with age was significant (p < 0.05) for PDFF of the sacrum (men (m): r = 0.58; women (w): r = 0.54), L5 (m: r = 0.58; w: r = 0.54), the gluteal (m: r = 0.51; w: r = 0.44) and paraspinal (m: r = 0.36; w: r = 0.49) muscles in both genders. BMI correlated significantly with the paraspinal musculature in men (r = 0.46) and women (r = 0.33). Correlation testing revealed significant correlations (p < 0.05) between the two osseous (m: r = 0.63, w: r = 0.75) and the muscle compartments (m: r = 0.63, w: r = 0.33) in both genders. Bone marrow and muscle fat infiltration patterns were not significantly associated with each other at the sacral and lower lumbar spine region. The presented data suggest that the two compartments may have distinct pathophysiological fat infiltration patterns. However, further clinical studies are needed to support the results.

Association of thigh and paraspinal muscle composition in young adults using chemical shift encoding-based water-fat MRI.

Paraspinal and thigh muscles comprise the major muscle groups of the body. We investigated the composition of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups and their association to each other using chemical shift encoding-based water-fat magnetic resonance imaging (MRI) in adult volunteers. Our aim was to elucidate fat distribution patterns within these muscle groups. Thirty volunteers [15 males, age: 30.5±4.9 years, body mass index (BMI): 27.6±2.8 kg/m2 and 15 females, age: 29.9±7.0 years, BMI: 25.8±1.4 kg/m2] were recruited for this study. A six-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation at the lumbar spine and bilateral thigh. Proton density fat fraction (PDFF), cross-sectional area (CSA) and contractile mass index (CMI) of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups were determined bilaterally and averaged over both sides. CSA and CMI values calculated for the erector spinae, psoas, quadriceps and hamstring muscle groups showed significant differences between men and women (P<0.05). With regard to PDFF measurement only the erector spinae showed significant differences between men and women (9.5%±2.4% vs. 11.7%±2.8%, P=0.015). The CMI of the psoas muscle as well as the erector spinae muscle showed significant correlations with the quadriceps muscle (r=0.691, P<0.0001 and r=0.761, P<0.0001) and the hamstring group (r=0.588, P=0.001 and r=0.603, P<0.0001). CMI values of the erector spinae and psoas muscles were associated with those of the quadriceps femoris and hamstring musculature. These findings suggest a concordant spatial fat accumulation within the analyzed muscles in young adults and warrants further investigations in ageing and diseased muscle.

Associations Between Lumbar Vertebral Bone Marrow and Paraspinal Muscle Fat Compositions-An Investigation by Chemical Shift Encoding-Based Water-Fat MRI.

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.

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

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. 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. 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). 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. • 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.

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.