Low Fat Fraction Research Articles

Hepatic steatosis modeling and MRI signal simulations for comparison of single- and dual-R2* models and estimation of fat fraction at 1.5T and 3T

Background and objectiveMagnetic resonance imaging (MRI) has emerged as a noninvasive clinical tool for assessment of hepatic steatosis. Multi-spectral fat-water MRI models, incorporating single or dual transverse relaxation decay rate(s) (R2*) have been proposed for accurate fat fraction (FF) estimation. However, it is still unclear whether single- or dual-R2* model accurately mimics in vivo signal decay for precise FF estimation and the impact of signal-to-noise ratio (SNR) on each model performance. Hence, this study aims to construct virtual steatosis models and synthesize MRI signals with different SNRs to systematically evaluate the accuracy of single- and dual-R2* models for FF and R2* estimations at 1.5T and 3.0T. MethodsRealistic hepatic steatosis models encompassing clinical FF range (0–60 %) were created using morphological features of fat droplets (FDs) extracted from human liver biopsy samples. MRI signals were synthesized using Monte Carlo simulations for noise-free (SNRideal) and varying SNR conditions (5–100). Fat-water phantoms were scanned with different SNRs to validate simulation results. Fat water toolbox was used to calculate R2* and FF for both single- and dual-R2* models. The model accuracies in R2* and FF estimates were analyzed using linear regression, bias plot and heatmap analysis. ResultsThe virtual steatosis model closely mimicked in vivo fat morphology and Monte Carlo simulation produced realistic MRI signals. For SNRideal and moderate-high SNRs, water R2* (R2*W) by dual-R2* and common R2* (R2*com) by single-R2* model showed an excellent agreement with slope close to unity (0.95–1.01) and R2 > 0.98 at both 1.5T and 3.0T. In simulations, the R2*com-FF and R2*W-FF relationships exhibited slopes similar to in vivo calibrations, confirming the accuracy of our virtual models. For SNRideal, fat R2* (R2*F) was similar to R2*W and dual-R2* model showed slightly higher accuracy in FF estimation. However, in the presence of noise, dual-R2* produced higher FF bias with decreasing SNR, while leading to only marginal improvement for high SNRs and in regions dominated by fat and water. In contrast, single-R2* model was robust and produced accurate FF estimations in simulations and phantom scans with clinical SNRs. ConclusionOur study demonstrates the feasibility of creating virtual steatosis models and generating MRI signals that mimic in vivo morphology and signal behavior. The single-R2* model consistently produced lower FF bias for clinical SNRs across entire FF range compared to dual-R2* model, hence signifying that single-R2* model is optimal for assessing hepatic steatosis.

Differentiation between normal and metastatic lymph nodes in patients with skin melanoma: Preliminary findings using a DIXON-based whole-body MRI approach

PurposeMetastatic melanoma lymph nodes (MMLns) might be challenging to detect on MR-WBI, as both MMLns and normal lymph nodes (NLns) can show restricted water diffusion. Our purpose is to assess the potential contribution of the DIXON sequence in differentiating MMLns from NLns. Material and methodsWe followed a cohort of 107 patients with stage IIIb/c and IV skin melanoma for 32 months using MR-WBI with DIXON, STIR, and DWI/ADC sequences. We compared signal intensity (SI) values of MMLns and NLns in the four series of the DIXON sequence (in/out-of-phase, fat_only, and water_only series). The fat fraction (SIfat_only/SIin) and the long:short axis ratio of MMLns were calculated. The fat fraction was also calculated in the fatty hila of NLns. ResultsAll MMLns (8 from 7 patients) showed SIout>SIin with a mean fat fraction of 10%. In 40 normal fatty hila (25 patients), the proportion of SIout>SIin was 100% and mean fat fraction was 89% (p<0.001 for fat fraction, Mann-Whitney U-test). In the cortex of NLns, a SIout>SIin pattern was identified in 41/113 cases from 19/40 patients. The median long:short axis ratio in MMLns was 1.13 (range 1.03–1.25). ConclusionThe combination of three features of MMLns (SIout>SIin, low-fat fraction and rounded shape) might hold promise in differentiating NLns from MMLns in patients with skin melanoma. Further research is warranted due to the small number of MMLns in our cohort.

Understanding ADC variation by fat content effect using a dual-function MRI phantom

BackgroundA dual-function phantom designed to quantify the apparent diffusion coefficient (ADC) in different fat contents (FCs) and glass bead densities (GBDs) to simulate the human tissues has not been documented yet. We propose a dual-function phantom to quantify the FC and to measure the ADC at different FCs and different GBDs.MethodsA fat-containing diffusion phantom comprised by 30 glass-bead-containing fat-water emulsions consisting of six different FCs (0, 10, 20, 30, 40, and 50%) multiplied by five different GBDs (0, 0.1, 0.25, 0.5, and 1.0 g/50 mL). The FC and ADC were measured by the “iterative decomposition of water and fat with echo asymmetry and least squares estimation-IQ,” IDEAL-IQ, and single-shot echo-planar diffusion-weighted imaging, SS-EP-DWI, sequences, respectively. Linear regression analysis was used to evaluate the relationship among the fat fraction (FF) measured by IDEAL-IQ, GBD, and ADC.ResultsThe ADC was significantly, negatively, and linearly associated with the FF (the linear slope ranged from -0.005 to -0.017, R2 = 0.925 to 0.986, all p < 0.001). The slope of the linear relationship between the ADC and the FF, however, varied among different GBDs (the higher the GBD, the lower the slope). ADCs among emulsions across different GBDs and FFs were overlapped. Emulsions with low GBDs plus high FFs shared a same lower ADC range with those with median or high GBDs plus median or lower FFs.ConclusionsA novel dual-function phantom simulating the human tissues allowed to quantify the influence of FC and GBD on ADC.Relevance statementThe study developed an innovative dual-function MRI phantom to explore the impact of FC on ADC variation that can affect clinical results. The results revealed the superimposed effect on FF and GBD density on ADC measurements.Key points• A dual-function phantom made of glass bead density (GBD) and fat fraction (FF) emulsion has been developed.• Apparent diffusion coefficient (ADC) values are determined by GBD and FF.• The dual-function phantom showed the mutual ADC addition between FF and GBD.Graphical

Evaluation of masticatory muscles in temporomandibular joint disorder patients using quantitative MRI fat fraction analysis-Could it be a biomarker?

Temporomandibular joint disorders (TMDs) are closely related to the masticatory muscles, but objective and quantitative methods to evaluate muscle are lacking. IDEAL-IQ, a type of chemical shift-encoded magnetic resonance imaging (CSE-MRI), can quantify the fat fraction (FF). The purpose of this study was to develop an MR IDEAL-IQ-based method for quantitative muscle diagnosis in TMD patients. A total of 65 patients who underwent 3 T MRI scans, including CSE-MRI sequences, were retrospectively included. MRI diagnoses and clinical data were reviewed. There were 19 patients in the normal group and 46 patients in the TMD group with unilateral disc displacement. The TMD group was subdivided into those with and without clenching. The right and left FF values of the masseter, medial, and lateral pterygoid muscles were measured twice by two oral radiologists on CSE-MRI, and the average value was used. FF measurements using CSE-MRI showed excellent intra- and inter-observer agreement (ICC > 0.889 for both). There were no statistically significant differences between the right and left FF values in the masseter, medial pterygoid, and lateral pterygoid of the normal group (p > 0.05). A statistically significant difference was found in the TMD group without clenching, in which the masseter muscle had a statistically significantly lower FF value on the disc displacement side (3.94 ± 1.61) than on the normal side (4.52 ± 2.24) (p < 0.05). CSE-MRI, which can reproducibly quantify muscle FF values, is expected to be a biomarker for objective muscle evaluation in TMD patients. The masseter muscle is expected to be particularly useful compared to other masticatory muscles, but further research is needed.

Quantitative Analysis of Whole-Body MRI for Accessing the Degree of Diffuse Infiltration Patterns and Identifying High Risk Cases of Newly Diagnosed Multiple Myeloma.

Accurate identification of high-risk multiple myeloma (HRMM) is important for prognostication. The degree of diffuse infiltration patterns on magnetic resonance imaging (MRI) is associated with patient prognosis in multiple myeloma. However, objective indexes to determine the degree of diffuse infiltration patterns are unavailable. To investigate whether qualitative and quantitative evaluations of diffuse infiltration patterns on MRI could identify HRMM. Retrospective. Totally, 180 patients (79 HRMM and 101 standard-risk MM) were assessed. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, and/or p53 mutations was considered to indicate HRMM. 3.0 T/diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon chemical-shift imaging Quant (mDIXON Quant), and short TI inversion recovery (STIR). Qualitative analysis involved assessing the degree of diffuse marrow infiltration (mild, moderate, or severe), and quantitative analysis involved evaluating apparent diffusion coefficient (ADC), fat fraction (FF), and T2* values. Clinical data such as sex, age, hemoglobin, serum albumin, serum calcium, serum creatinine, serum lactate dehydrogenase, β2-microglobulin, and bone marrow plasma cells (BMPCs) were also included. Univariate and multivariate analyses, receiver operating characteristic (ROC) curve. P < 0.05 was considered statistically significant. The high-risk group had significantly higher ADC and T2* and lower FF compared with the standard-risk group. Multivariate analysis indicated BMPCs as a significant independent risk factor for HRMM (odds ratio (OR) = 1.019, 95% CI 1.004-1.033), while FF was a significant independent protective factor associated with HRMM (OR = 0.972, 95% CI 0.946-0.999). The combination of BMPCs and FF achieved the highest areas under the curve (AUC) of 0.732, with sensitivity and specificity of 70.9% and 68.3%, respectively. Compared with qualitative analysis, FF value was independently associated with HRMM. The quantitative features of diffuse marrow infiltration on MRI scans are more effective in detecting HRMM. 3 TECHNICAL EFFICACY: Stage 2.

Use of IDEAL-IQ in Quantifying Femoral Bone Marrow Involvement in Gaucher Disease.

To quantitatively measure femoral bone marrow involvement in patients with Gaucher disease (GD) by using fat fraction (FF) derived from the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) technique. Bilateral femora of 23 patients with type 1 GD receiving low-dose imiglucerase treatment were prospectively scanned using structural magnetic resonance imaging sequences and an IDEAL-IQ sequence. Femoral bone marrow involvement was evaluated by both semiquantification (bone marrow burden [BMB] score based on magnetic resonance imaging structural images) and quantification (FF derived from IDEAL-IQ) methods. These patients were further divided into subgroups according to whether they underwent splenectomy or had bone complications. The interreader agreement of measurements and the correlation between FF and clinical status were statistically analyzed. In patients with GD, both BMB and FF evaluation of femora showed good interreader concordance (intraclass correlation coefficient = 0.98 and 0.99, respectively), and FF highly correlated with BMB score ( P < 0.001). The longer the duration of disease, the lower the FF ( P = 0.026). Femoral FF was lower in subgroups with splenectomy or bone complications than those without splenectomy or bone complications (0.47 ± 0.08 vs 0.60 ± 0.15, 0.51 ± 0.10 vs 0.61 ± 0.17, respectively, both P < 0.05). Femoral FF derived from IDEAL-IQ could be used to quantify femoral bone marrow involvement in patients with GD, and low bone marrow FF may predict worse outcomes of GD patients in this small-scale study.

Mid-life cyclists preserve muscle mass and composition: a 3D MRI study

Physical activity and a healthy lifestyle are crucial factors for delaying and reducing the effects of sarcopenia. Cycling has gained popularity in the last decades among midlife men. While the cardiovascular benefits of cycling and other endurance exercises have been extensively proved, the potential benefits of lifelong aerobic exercise on muscle health have not been adequately studied. Our aim was to quantify the benefits of cycling in terms of muscle health in middle-aged men, using magnetic resonance imaging. We ran a cross-sectional study involving two groups of middle-aged male adults (mean age 49 years, range 30–65) that underwent Dixon MRI of the pelvis. The groups consisted of 28 physically inactive (PI) and 28 trained recreational cyclists. The latter had cycled more than 7000 km in the last year and have been training for 15 years on average, while the PI volunteers have not practiced sports for an average of 27 years. We processed the Dixon MRI scans by labelling and computing the fat fraction (FF), volume and lean volume of gluteus maximus (GMAX) and gluteus medius (GMED); and measuring the volume of subcutaneous adipose tissue (SAT). We found that the cyclists group had lower FF levels, a measure of intramuscular fat infiltration, compared to the PI group for GMAX (PI median FF 21.6%, cyclists median FF 14.8%, p < 0.01) and GMED (PI median FF 16.0%, cyclists median FF 11.4%, p < 0.01). Cyclists had also larger GMAX and GMED muscles than the PI group (p < 0.01), after normalizing it by body mass. Muscle mass and fat infiltration were strongly correlated with SAT volume. These results suggest that cycling could help preserve muscle mass and composition in middle-aged men. Although more research is needed to support these results, this study adds new evidence to support public health efforts to promote cycling.

The Bone Biomarker of Quantitative Chemical Shift Imaging in Patients with Type 1 Gaucher Disease Receiving Low-Dose Long-Term Enzyme Replacement Therapy

Quantitative chemical shift imaging (QCSI) is the most sensitive imaging biomarker to assess bone marrow involvement in Gaucher disease. Widespread QCSI use is limited by test availability. Anecdotal reports describe two patients demonstrating significant improvement in fat fraction (FF) assessed by QCSI following a switch from imiglucerase to taliglucerase alfa. This analysis evaluated bone marrow involvement in adults with Type 1 Gaucher disease receiving low-dose enzyme replacement therapy (ERT) with imiglucerase and/or velaglucerase alfa. We report baseline data for 30 patients meeting eligibility criteria. Median (range) duration and dose of ERT were 18 (5-26) years and 30 (30-60) U/kg/month, respectively. Low FF scores (<0.30) were observed for seven patients (23%; 95% confidence interval, 10-42%) and were more common in females (n = 6) versus males (n = 1; p < 0.025); one female was menopausal. These baseline data demonstrate that prolonged low-dose ERT with imiglucerase or velaglucerase alfa led to an adequate bone response, assessed by QCSI, in the majority of patients. A minority of such patients with suboptimal bone response require therapeutic change. The next phase of the study will address the effect of switching to taliglucerase alfa on bone status for patients with less than optimal QCSI scores (<0.30).

Feasibility of joint mapping of triglyceride saturation and water longitudinal relaxation in a single breath hold applied to high fat-fraction adipose depots in the periclavicular anatomy

IntroductionSimultaneous mapping of triglyceride (TAG) saturation and tissue water relaxation may improve the characterization of the structure and function of anatomies with significant adipose tissue. While several groups have demonstrated in vivo TAG saturation imaging using MRI, joint mapping of relaxation and TAG saturation is understudied. Such mappings may avoid bias from physiological motion, if they can be done within a single breath-hold, and also account for static and applied magnetic field heterogeneity. MethodsWe propose a transient-state/MR fingerprinting single breath-hold sequence at 3 T, a low-rank reconstruction, and a parameter estimation pipeline that jointly estimates the number of double bonds (NDB), number of methylene interrupted double bonds (NMIDB), and tissue water T1, while accounting for non-ideal radiofrequency transmit scaling and off-resonance effects. We test the proposed method in simulations, in phantom against MR spectroscopy (MRS), and in vivo regions in and around high fat fraction (FF) periclavicular adipose tissue. Partial volume and multi-peak transverse relaxation effects are explored. ResultsThe simulation results demonstrate accurate NDB, NMIDB, and water T1 estimates across a range of NDB, NMIDB, and T1 values. In phantoms, the proposed method's estimates of NDB and NMIDB correlate with those from MR spectroscopy (Pearson correlation ≥0.98), while the water T1 estimates are concordant with a standard phantom. The NDB and NMIDB are sensitive to partial volumes of water, showing increasing bias at FF < 40%. This bias is found to be due to noise and transverse relaxation effects. The in vivo periclavicular adipose tissue has high FF (>90%). The adipose tissue NDB and NMIDB, and muscle T1 estimates are comparable to those reported in the literature. ConclusionRobust estimation of NDB, NMIDB at high FF and water T1 across a broad range of FFs are feasible using the proposed methods. Further reduction of noise and model bias are needed to employ the proposed technique in low FF anatomies and pathologies.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology

BackgroundLumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology.MethodsMultifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality.ResultsRelationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045).ConclusionFibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Differentiation of Diffuse Infiltration Pattern in Multiple Myeloma From Hyperplastic Hematopoietic Bone Marrow: Qualitative and Quantitative Analysis Using Whole-Body MRI.

The visual assessment used for diffuse infiltration of multiple myeloma (MM) is inadequate. It can be difficult to differentiate MM from hyperplastic hematopoietic bone marrow (HHBM) because the MRI signal characteristics overlap. To analyze the bone marrow diffuse signal changes on whole-body MRI caused by MM and HHBM. Retrospective. Thirty Four patients with MM (21 men and 13 women), 22 patients with HHBM (9 men and 13 women), and 15 healthy controls (9 men and 6 women). A 3.0 T MRI; diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon T1 fast field echo, and T2 STIR. Three radiologists analyzed the whole-body MRI alone and in combination with apparent diffusion coefficient (ADC) and fat fraction (FF) with qualitative and quantitative analysis. Normalized T1 and T2 signal intensities (nT1 and nT2) and signal-to-noise ratio (SNR) were obtained. Kruskal-Wallis and chi-square tests. The MM group had significantly higher ADC and significantly lower FF than HHBM and control groups. There was no significant difference in nT1, nT2 or SNR between MM and HHBM (P=0.932, P=0.097, and P=0.110, respectively). Receiver operating characteristic (ROC) analysis using ADC and FF cut-off values of 0.47 × 10-3 mm2 /sec and 20.63%, respectively. The AUC was 0.866 for ADC and 0.886 for FF. The quantitative analysis yielded better specificity (observer 1: 81.8% vs. 27.3%; observer 2: 68.2% vs. 22.7%; and observer 3: 72.7% vs. 18.2%) and a higher diagnostic accuracy (observer 1: 82.1% vs. 51.8%; observer 2: 80.4% vs. 50.0%; observer 3: 76.8% vs. 44.6%) than the qualitative analysis. Whole-body MRI combined with DWIBS and mDIXON could be used to differentiate between MM and HHBM. Combining the quantitative ADC and FF with the whole-body MRI improved the specificity and accuracy in differentiating these conditions. 3 TECHNICAL EFFICACY: Stage 2.

Preserved thenar muscles in non-ambulant Duchenne muscular dystrophy patients.

BackgroundClinical trials in Duchenne muscular dystrophy (DMD) focus primarily on ambulant patients. Results cannot be extrapolated to later disease stages due to a decline in targeted muscle tissue. In non‐ambulant DMD patients, hand function is relatively preserved and crucial for daily‐life activities. We used quantitative MRI (qMRI) to establish whether the thenar muscles could be valuable to monitor treatment effects in non‐ambulant DMD patients.MethodsSeventeen non‐ambulant DMD patients (range 10.2–24.1 years) and 13 healthy controls (range 9.5–25.4 years) underwent qMRI of the right hand at 3 T at baseline. Thenar fat fraction (FF), total volume (TV), and contractile volume (CV) were determined using 4‐point Dixon, and T2water was determined using multiecho spin‐echo. Clinical assessments at baseline (n = 17) and 12 months (n = 13) included pinch strength (kg), performance of the upper limb (PUL) 2.0, DMD upper limb patient reported outcome measure (PROM), and playing a video game for 10 min using a game controller. Group differences and correlations were assessed with non‐parametric tests.ResultsTotal volume was lower in patients compared with healthy controls (6.9 cm3, 5.3–9.0 cm3 vs. 13.0 cm3, 7.6–15.8 cm3, P = 0.010). CV was also lower in patients (6.3 cm3, 4.6–8.3 cm3 vs. 11.9 cm3, 6.9–14.6 cm3, P = 0.010). FF was slightly elevated (9.7%, 7.3–11.4% vs. 7.7%, 6.6–8.4%, P = 0.043), while T2water was higher (31.5 ms, 30.0–32.6 ms vs. 28.1 ms, 27.8–29.4 ms, P < 0.001). Pinch strength and PUL decreased over 12 months (2.857 kg, 2.137–4.010 to 2.243 kg, 1.930–3.339 kg, and 29 points, 20–36 to 23 points, 17–30, both P < 0.001), while PROM did not (49 points, 36–57 to 44 points, 30–54, P = 0.041). All patients were able to play for 10 min at baseline or follow‐up, but some did not comply with the study procedures regarding this endpoint. Pinch strength correlated with TV and CV in patients (rho = 0.72 and rho = 0.68) and controls (both rho = 0.89). PUL correlated with TV, CV, and T2water (rho = 0.57, rho = 0.51, and rho = −0.59).ConclusionsLow thenar FF, increased T2water, correlation of muscle size with strength and function, and the decrease in strength and function over 1 year indicate that the thenar muscles are a valuable and quantifiable target for therapy in later stages of DMD. Further studies are needed to relate these data to the loss of a clinically meaningful milestone.

Morphological characterization of hepatic steatosis and Monte Carlo modeling of MRI signal for accurate quantification of fat fraction and relaxivity.

Chemical-shift-based fat-water MRI signal models with single- or dual-R2 * correction have been proposed for quantification of fat fraction (FF) and assessment of hepatic steatosis. However, there is a void in our understanding of which model truly mimics the underlying biophysical mechanism of steatosis on MRI signal relaxation. The purpose of this study is to morphologically characterize and build realistic steatosis models from histology and synthesize MRI signal using Monte Carlo simulations to investigate the accuracy of single- and dual-R2 * models in quantifying FF and R2 *. Fat morphology was characterized by performing automatic segmentation on 16 mouse liver histology images and extracting the radius, nearest neighbor (NN) distance, and regional anisotropy of fat droplets. A gamma distribution function (GDF) was used to generalize extracted features, and regression analysis was performed to derive relationships between FF and GDF parameters. Virtual steatosis models were created based on derived morphological and statistical descriptors, and the MRI signal was synthesized at 1.5 T and 3 T. R2 * and FF values were calculated using single- and dual-R2 * models and compared with in vivo R2 *-FF calibrations and simulated FFs. The steatosis models generated with regional anisotropy and NN distribution closely mimicked the true in vivo fat morphology. For both R2 * models, predicted R2 * values showed positive correlation with FFs, with slopes similar to those of the in vivo calibrations (P > 0.05), and predicted FFs showed excellent agreement with true FFs (R2 > 0.99), with slopes close to unity. Our study, hence, demonstrates the proof of concept for generating steatosis models from histologic data and synthesizing MRI signal to show the expected signal relaxation under conditions of steatosis. Our results suggest that a single R2 * is sufficient to accurately estimate R2 * and FF values for lower FFs, which agrees with in vivo studies. Future work involves characterizing and building steatosis models at higher FFs and testing single- and dual-R2 * models for accurate assessment of steatosis.

Bone Marrow Involvement in Patients with Type 1 Gaucher Disease Receiving Low-Dose Long Term Enzyme Replacement Therapy (median 18 years)

Bone complications are the most dramatic and life-impairing outcomes of type 1 Gaucher disease (GD1), a common lysosomal storage disorder. Bone marrow infiltration by Gaucher cells substantially decreases the bone marrow fat fraction (FF), and the extent of this reduction correlates with the overall severity of skeletal manifestations in this disorder. Previous studies have demonstrated that the degree of infiltration can best be estimated by magnetic imaging resonance (MRI)-based quantitative chemical shift imaging (QCSI) and that the fat fraction (FF) score so derived can predict the risk of clinically important bone events. The aim of this study was to evaluate bone marrow involvement in GD1 patients who had received enzyme replacement therapy (ERT) for at least 5 years. Methods: Patients from SZMC Gaucher unit, ≥ 18 years, who were treated with ERT for ≥ 5 years, with a stable dose in the previous 6 months, were recruited. Patients taking another experimental drug, with past exposure to taliglucerase-alfa, presence of any medical, emotional, behavioral or psychological condition were excluded. Energy x-ray absorptiometry (DEXA) was performed at SZMC and the QSCI was performed at the Academic Medical Center in Amsterdam, Netherlands as previously described [Mass et al, Am J Radiol 2002:179:961-965]. A QCSI score of &lt;0.30 was indicative of bone at risk. This investigator initiated clinical trial was approved IRB at SZMC and AMC and sponsored by Pfizer. Study number registration- MOH-2017-04-000351. Results: Thirty patients (13 females) at a median (range) age of 46 (19-71) years consented to participate in this study and to perform the QCSI test. GBA mutations of study patients included N370S homozygote (n=12), N370S compound heterozygote (n=17), and T431 homozygote (n=1). The median (range) duration of ERT was 18 (5-26) years. Thirteen patients were receiving imiglucerase as the primary ERT [median (range) duration, 19 (9-26) years], five patients were receiving velaglucerase alfa [median (range) duration, 11 ( 5-12) years], and 12 patients converted from imiglucerase to velaglucerase alfa [median (range) duration, 7 (6-10) years]. The majority of patients received low-dose regimen, i.e. 15 Units/kg/2 weeks (Table 1). The median (range) T score for lumbar spine from DEXA scans, available for 26 of 30 patients, was −1.3 (−2.8-0.0). The median (range) QCSI score was 0.42 (0.24-0.66). Seven patients, 23% (95% confidence interval 10%-42%), had abnormal QCSI FF scores (&lt;0.30). Abnormal QSCI score was more common in female compared to male (Table 1) (p=0.025). Only one of these was menopausal. No differences were found in age, gender, genotype, history of splenectomy, duration and type of ERT and GD-related parameters between those with QSCI score of bone at risk to those with normal score (Table 1). In summary, these findings demonstrate that, despite prolonged treatment with imiglucerase and/or velalgucerase alfa, 23% of patients still had QCSI scores indicative of an inadequate response in bones. Nevertheless, most patients with prolonged low-dose ERT maintain a normal QCSI, indicative of a positive bone status. The higher prevalence of women in the cohort with low FF is not related to menopausal phase and remains unexplained. As no other patient-related nor GD-related parameter predicted abnormal bone marrow infiltration, a more widely available, quantitative measure of bone marrow infiltration is required for the assessment of response in bones to ERT for patients with GD1. The second phase of this study will evaluate the impact of a switch to a third ERT in those patients from this study with QCSI scores of &lt;0.30. These patients will be offered treatment with taliglucerase alfa at equivalent doses and subsequent reassessment of any impact on clinical symptoms and QCSI scores evaluated. Disclosures Revel-Vilk: Takeda: Honoraria, Other: Travel, Research Funding; Prevail therapeutics: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding. Szer:Alexion: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding; Prevail Therapeutics: Honoraria, Other: Travel, Research Funding. Zimran:Centogene: Other: research grant; Shire: Consultancy, Honoraria, Research Funding; TAKEDA: Honoraria; Pfize: Honoraria, Research Funding; Bio-events: Honoraria; Targeted Cell Therapies: Consultancy; Prevail Therapeutics: Consultancy.

Study of lipid metabolism by estimating the fat fraction in different breast tissues and in various breast tumor sub-types by in vivo 1H MR spectroscopy

PurposeTo evaluate the utility of fat fraction (FF) for the differentiation of different breast tissues and in various breast tumor subtypes using in vivo proton (1H) magnetic resonance spectroscopy (MRS). Methods1H MRS was performed on 68 malignant, 35 benign, and 30 healthy volunteers at 1.5 T. Malignant breast tissues of patients were characterized into different subtypes based on the differences in the expression of hormone receptors and the FF was calculated. Further, the sensitivity and specificity of FF to differentiate malignant from benign and from normal breast tissues of healthy volunteers was determined using receiver operator curve (ROC) analysis. ResultsA significantly lower FF of malignant (median 0.12; range 0.01–0.70) compared to benign lesions (median 0.28; range 0.02–0.71) and normal breast tissue of healthy volunteers (median 0.39; range 0.06–0.76) was observed. No significant difference in FF was seen between benign lesions and normal breast tissues of healthy volunteers. Sensitivity and specificity of 75% and 68.6%, respectively was obtained to differentiate malignant from benign lesions. For the differentiation of malignant from healthy breast tissues, 76% sensitivity and 74.5% specificity was achieved. Higher FF was seen in patients with ER−/PR− status as compared to ER+/PR+ patients. Similarly, FF of HER2neu+ tumors were significantly higher than in HER2neu− breast tumors. ConclusionThe results showed the potential of in vivo 1H MRS in providing insight into the changes in the fat content of different types of breast tissues and in various breast tumor subtypes.

High-Resolution MR Imaging of Muscular Fat Fraction-Comparison of Three T2-Based Methods and Chemical Shift-Encoded Imaging.

Chemical shift-encoded imaging (CSEI) is the most common magnetic resonance imaging fat–water separation method. However, when high spatial resolution fat fraction (FF) images are desired, CSEI might be challenging owing to the increased interecho spacing. Here, 3 T2-based methods have been assessed as alternative methods for obtaining high-resolution FF images. Images from the calf of 10 healthy volunteers were acquired; FF maps were then estimated using 3 T2-based methods (2- and 3-parameter nonlinear least squares fit and a Bayesian probability method) and CSEI for reference. In addition, simulations were conducted to characterize the performance of various methods. Here, all T2-based methods resulted in qualitatively improved high-resolution FF images compared with high-resolution CSEI. The 2-parameter fit showed best quantitative agreement to low-resolution CSEI, even at low FF. The estimated T2-values of fat and water, and the estimated muscle FF of the calf, agreed well with previously published data. In conclusion, T2-based methods can provide improved high-resolution FF images of the calf compared with the CSEI method.

Characterization of T1 bias in skeletal muscle from fat in MOLLI and SASHA pulse sequences: Quantitative fat-fraction imaging with T1 mapping.

To characterize the effects of fat on commonly used T1 mapping sequences and evaluate a new method of quantitative fat fraction (FF) imaging for low fractions based on the modulation of T1 values by the fat pool. Bloch equation simulations and phantom and in vivo (skeletal muscle) experiments were used to characterize the response of the modified Look-Locker inversion recovery (MOLLI) and saturation recovery single-shot acquisition (SASHA) T1 mapping sequences to fat-water systems with known FFs (0%-10%) at 1.5T. FFs were measured with single voxel spectroscopy and Dixon imaging methods. A new T1 -based FF imaging method was evaluated using Monte Carlo simulations and phantom and in vivo experiments. SASHA and MOLLI had similar T1 dependence on FF, with characteristic under- or overestimation of T1 values as a function of off-resonance frequency (30-70 ms variation in native T1 per 1% FF). FF maps generated from the SASHA method yielded a low variability of ±0.25% for a signal-to-noise ratio of 150:1 in the nonsaturation image, with good agreement with spectroscopy and a performance that is superior to that of Dixon methods at low FFs. Fat results in negative or positive shifts in native tissue T1 measured with MOLLI and SASHA over a narrow range of off-resonance frequencies; T1 shifts from fat can be used to accurately quantify FF. Magn Reson Med 77:237-249, 2017. © 2016 Wiley Periodicals, Inc.

Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls

IntroductionChildren with type 1 diabetes have been identified as a risk group for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total hepatic fat fraction and fat distribution across Couinaud segments in children with type 1 diabetes and controls and the relation of hepatic fat to plasma and anthropometric parameters. MethodsHepatic fat fraction and fat distribution across Couinaud segments were measured with magnetic resonance imaging (MRI) in 22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric data were collected. ResultsNo children had NAFLD. Children with type 1 diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls (median 1.8%), and their fat had a different segmental distribution. The fat fraction of segment V was the most representative of the liver as a whole. An incidental finding was that diabetes patients treated with multiple daily injections of insulin (MDI) had a fat distribution more similar to controls than patients with continuous subcutaneous insulin infusion (CSII). ConclusionsIn children with type 1 diabetes, NAFLD may be less common than recent studies have suggested. Children with type 1 diabetes may have a lower fat fraction and a different fat distribution in the liver than controls. Diabetes treatment with MDI or CSII may affect liver fat, but this needs to be confirmed in a larger sample of patients. The heterogeneity of hepatic fat infiltration may affect results when liver biopsy is used for diagnosing fatty liver.

Distinct Disease Phases in Muscles of Facioscapulohumeral Dystrophy Patients Identified by MR Detected Fat Infiltration

Facioscapulohumeral muscular dystrophy (FSHD) is an untreatable disease, characterized by asymmetric progressive weakness of skeletal muscle with fatty infiltration. Although the main genetic defect has been uncovered, the downstream mechanisms causing FSHD are not understood. The objective of this study was to determine natural disease state and progression in muscles of FSHD patients and to establish diagnostic biomarkers by quantitative MRI of fat infiltration and phosphorylated metabolites. MRI was performed at 3T with dedicated coils on legs of 41 patients (28 men/13 women, age 34–76 years), of which eleven were re-examined after four months of usual care. Muscular fat fraction was determined with multi spin-echo and T1 weighted MRI, edema by TIRM and phosphorylated metabolites by 3D 31P MR spectroscopic imaging. Fat fractions were compared to clinical severity, muscle force, age, edema and phosphocreatine (PCr)/ATP. Longitudinal intramuscular fat fraction variation was analyzed by linear regression. Increased intramuscular fat correlated with age (p<0.05), FSHD severity score (p<0.0001), inversely with muscle strength (p<0.0001), and also occurred sub-clinically. Muscles were nearly dichotomously divided in those with high and with low fat fraction, with only 13% having an intermediate fat fraction. The intramuscular fat fraction along the muscle’s length, increased from proximal to distal. This fat gradient was the steepest for intermediate fat infiltrated muscles (0.07±0.01/cm, p<0.001). Leg muscles in this intermediate phase showed a decreased PCr/ATP (p<0.05) and the fastest increase in fatty infiltration over time (0.18±0.15/year, p<0.001), which correlated with initial edema (p<0.01), if present. Thus, in the MR assessment of fat infiltration as biomarker for diseased muscles, the intramuscular fat distribution needs to be taken into account. Our results indicate that healthy individual leg muscles become diseased by entering a progressive phase with distal fat infiltration and altered energy metabolite levels. Fat replacement then relatively rapidly spreads over the whole muscle.

WE-C-WAB-06: Effects of Radiation On Functional Bone Marrow in Patients with Pelvic Malignancies

Purpose: To test the hypothesis that pelvic bone marrow fat fraction (FF) (i.e., quantity of fat relative to water) varies with glucose metabolism and radiation dose in patients undergoing pelvic radiotherapy. Methods: 34 patients with pelvic malignancies were enrolled from 2009‐2012 on prospective trials; 31 received concurrent chemotherapy. All patients underwent baseline 18F‐FDG‐PET and quantitative MRI with IDEAL‐IQ. 9 patients underwent PET/CT simulation, 15 PET/CT, and 10 PET‐only. 18 and 14 patients underwent IDEAL‐IQ at mid‐treatment and 1–3 weeks post‐treatment, respectively. PET‐only scans were rigidly registered to the planning CT (pCT). PET/CT and IDEAL‐IQ scans were deformably registered to the pCT (Velocity AI, Atlanta, GA). Each image was resampled to the pCT, creating a database of FF, dose, and body weight‐standardized uptake value (SUVbw) for each voxel. Analyses were performed on pelvic bone from L5 to ischia. Spearman rank correlation coefficients (SRCC) were estimated comparing SUVbw and dose vs. FF1, ΔFF21, and ΔFF31. FF1 represents FF at baseline and ΔFF21 and ΔFF31 represent change in FF from baseline to mid‐and post‐treatment, respectively. Mean SRCCs were tested for significance using a 2‐sided t‐test. Results: Data analysis was completed for 15 patients (13 gynecologic, 7 anal cancer). We observed a significant negative correlation between SUVbw and FF1, and significant positive correlations between SUVbw and ΔFF21 and ΔFF31 (Table), indicating that high metabolic activity correlated with lower FF (a surrogate for red marrow) and increased conversion to fat (yellow marrow) during radiotherapy. We observed significant positive correlations between radiation dose and ΔFF21 and ΔFF31, indicating that regions of higher dose were more likely to convert to fat (Table). No correlation was observed between dose and FF1. Conclusion: Preliminary results suggest that red marrow has higher metabolic activity, and is more likely to convert to yellow marrow during radiotherapy, in a dose‐dependent manner. Funding has been provided by NIH R21 Research Grant (#CA162718‐01) and by the American Society of Clinical Oncology.