Mean Proton Density Fat Fraction Research Articles

Evaluation of Hematopoiesis and Disease Status in Patients with Hematologic Malignancies Using Whole-Body Bone Marrow Imaging with 18 F-FLT PET/MRI

Introduction Bone marrow examination is primarily focused on a limited region of the ilium, thereby inadequately assessing systemic hematopoiesis or residual tumor cells after therapy. Magnetic resonance imaging (MRI) of the spine can examine the fat marrow, but does not provide a direct assessment of hematopoietic cells. The use of the radiopharmaceutical 3‘-deoxy-3‘- 18F-fluorothymidine ( 18F-FLT) positron emission tomography (PET), which measures nucleic acid synthesis, can provide a quantifiable means of assessing hematopoietic cell proliferation. The combination of whole-body MRI and 18F-FLT PET may provide a more accurate assessment of whole-body bone marrow hematopoiesis in hematologic malignancies. Methods A prospective, open-label, exploratory study (UMIN000041491) was conducted to evaluate hematopoiesis using 18F-FLT PET/MRI imaging in patients planned for allogeneic hematopoietic stem cell transplantation. Subjects were patients over 20 years of age with hematologic malignancies who underwent 18F-FLT PET/MRI imaging before transplantation and at 50 and 180 days after transplantation. After an intravenous injection of 185 MBq 18F-FLT, patients were transferred to a simultaneous 3.0 T PET/MR scanner (Signa PET/MR; GE Healthcare, Waukesha, WI). The PET acquisition was performed in 3D mode with a 5.5 min/bed position (89 slices/bed) and a 24-slice overlap in 5 to 6 beds. The percentage of fat marrow was determined using MRI proton density fat fraction (PDFF) with a 1 cm 2 region of interest at 26 sites: cervical spine (C2-C7), thoracic spine (Th1-Th12), lumbar spine (L1-L5), and superior posterior iliac spine (two sites on each side). Similarly, the standardized uptake value (SUV) of 18F-FLT was measured. Results Thirteen patients with hematologic malignancies (8 with acute myeloid leukemia, 2 with acute lymphoblastic leukemia, and 3 with malignant lymphoma) were evaluated between August 2020 and April 2023. The median age of the patients was 46 years (range: 23 ~ 65). Seven patients underwent cord blood transplantation, while the remainder received peripheral blood stem cell transplantation. Prior to transplantation, all 13 patients underwent 18F-FLT PET/MRI scans. After transplantation, due to treatment-related death or worsening of the primary disease, 11 patients underwent scans on day 50, while 8 patients underwent scans on day 180, resulting in a total of 32 evaluable scans. In the 28 cases in hematologic remission at imaging, mean PDFF values were higher in the iliac (63.3% ± standard deviation 13.9) and lumbar (60.4% ± 14.9) than in the thoracic (47.2% ± 17.1) and cervical (37.5% ± 14.8) spines. Conversely, mean 18F-FLT SUV was higher in the thoracic (6.98 ± 2.31) and cervical (6.82 ± 2.03) than in the lumbar (5.06 ± 2.39) and iliac (3.95 ± 1.88) spine. This site-specific disparity in PDFF and 18F-FLT SUV was consistent both before and after transplantation. In all 32 cases, the median correlation coefficient between PDFF and 18F-FLT SUV was -0.60 (range: -0.92 ~ 0.17, Pearson's cumulative correlation coefficient), and 25 cases (78.1%) had a negative correlation coefficient below -0.4. Comparing the 12 cases with residual disease (4 cases with hematologic non-remission and 8 cases with hematologic remission but abnormal G-banding or quantitative polymerase chain reaction) with the 20 cases in complete remission, the correlation between PDFF and 18F-FLT SUV was significantly weaker in the residual disease group (-0.37 vs. -0.75, p<0.001, Mann-Whitney U test). When the correlation coefficient threshold was set at -0.57, the ROC curve for determining residual disease had an AUC of 0.86, a sensitivity of 83.3%, and a specificity of 85.0%. Discussion It is important to understand that the fat marrow and hematopoiesis degree in the iliac bone differs from that in the thoracic and cervical spine throughout the transplantation process, thereby influencing the disease status evaluation in hematological malignancies. The correlation between PDFF and 18F-FLT SUV, which is strong in cases of remission, weakens in cases of residual disease, even at the level of minimal residual disease. This discrepancy may reflect aberrant tumorigenic cell proliferation that differs from the norm. Thus, 18F-FLT PET/MRI was useful in understanding the hematopoietic and disease state of the systemic bone marrow in patients with hematologic malignancies.

Myosteatosis and bone marrow adiposity are not associated among postmenopausal women with fragility fractures.

Although paravertebral intramuscular fatty infiltration (known as myosteatosis) following a vertebral fracture is well-known, scarce data are available regarding interactions between muscle, bone, and other fat depots. Based on a homogeneous cohort comprising postmenopausal women with or without a history of fragility fracture, we aimed to better depict the interrelationship between myosteatosis and bone marrow adiposity (BMA). 102 postmenopausal women were included, 56 of whom had a fragility fracture. Mean proton density fat fraction (PDFF) was measured in the psoas (PDFFPsoas) and paravertebral (PDFFParavertebral) muscles at the lumbar level, as well as in the lumbar spine and non-dominant hip using chemical shift encoding-based water-fat imaging. Visceral adipose tissue (VAT) and total body fat (TBF) were assessed using dual X-ray absorptiometry. Statistical models were adjusted for age, weight, height (all comparisons), and bone mineral density (when considering BMA). PDFF in the psoas and paravertebral muscles was higher in the fracture group compared to controls even after adjustment for age, weight, and height (PDFFPsoas = 17.1 ± 6.1% versus 13.5 ± 4.9%, p=0.004; PDFFParavertebral = 34.4 ± 13.6% versus 24.9 ± 8.8%, p=0.002). Higher PDFFParavertebral was associated with lower PDFF at the lumbar spine (β = -6.80 ± 2.85, p=0.022) among controls but not in the fracture group. In both groups, a significant relationship between higher PDFFPsoas and higher VAT was observed (β = 20.27 ± 9.62, p=0.040 in the fracture group, and β = 37.49 ± 8.65, p<0.001 in the control group). Although solely observed among controls, a similar relationship was observed between PDFFParavertebral and TBF (β = 6.57 ± 1.80, p<0.001). No significant association was observed between BMA and other fat depots. Myosteatosis is not associated with BMA among postmenopausal women with fragility fractures. Whereas myosteatosis was associated with other fat depots, BMA appears uniquely regulated.

Automated shape-independent assessment of the spatial distribution of proton density fat fraction in vertebral bone marrow

This work proposes a method for automatic standardized assessment of bone marrow volume and spatial distribution of the proton density fat fraction (PDFF) in vertebral bodies. Intra- and interindividual variability in size and shape of vertebral bodies is a challenge for comparable interindividual evaluation and monitoring of changes in the composition and distribution of bone marrow due to aging and/or intervention. Based on deep learning image segmentation, bone marrow PDFF of single vertebral bodies is mapped to a cylindrical template and corrected for the inclination with respect to the horizontal plane. The proposed technique was applied and tested in a cohort of 60 healthy (30 males, 30 females) individuals. Obtained bone marrow volumes and mean PDFF values are comparable to former manual and (semi-)automatic approaches. Moreover, the proposed method allows shape-independent characterization of the spatial PDFF distribution inside vertebral bodies.

Assessing breast density using the chemical-shift encoding-based proton density fat fraction in 3-T MRI

ObjectivesThere is a clinical need for a non-ionizing, quantitative assessment of breast density, as one of the strongest independent risk factors for breast cancer. This study aims to establish proton density fat fraction (PDFF) as a quantitative biomarker for fat tissue concentration in breast MRI and correlate mean breast PDFF to mammography.MethodsIn this retrospective study, 193 women were routinely subjected to 3-T MRI using a six-echo chemical shift encoding-based water-fat sequence. Water-fat separation was based on a signal model accounting for a single T2* decay and a pre-calibrated 7-peak fat spectrum resulting in volumetric fat-only, water-only images, PDFF- and T2*-values. After semi-automated breast segmentation, PDFF and T2* values were determined for the entire breast and fibroglandular tissue. The mammographic and MRI-based breast density was classified by visual estimation using the American College of Radiology Breast Imaging Reporting and Data System categories (ACR A-D).ResultsThe PDFF negatively correlated with mammographic and MRI breast density measurements (Spearman rho: −0.74, p < .001) and revealed a significant distinction between all four ACR categories. Mean T2* of the fibroglandular tissue correlated with increasing ACR categories (Spearman rho: 0.34, p < .001). The PDFF of the fibroglandular tissue showed a correlation with age (Pearson rho: 0.56, p = .03).ConclusionThe proposed breast PDFF as an automated tissue fat concentration measurement is comparable with mammographic breast density estimations. Therefore, it is a promising approach to an accurate, user-independent, and non-ionizing breast density assessment that could be easily incorporated into clinical routine breast MRI exams.Key Points• The proposed PDFF strongly negatively correlates with visually determined mammographic and MRI-based breast density estimations and therefore allows for an accurate, non-ionizing, and user-independent breast density measurement.• In combination with T2*, the PDFF can be used to track structural alterations in the composition of breast tissue for an individualized risk assessment for breast cancer.

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents. ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT. MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis. ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96). ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.

Associations of Texture Features of Proton Density Fat Fraction Maps between Lumbar Vertebral Bone Marrow and Paraspinal Musculature.

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.

MRI-based quantification of renal fat in obese individuals using different image analysis approaches.

The purpose of this study was to evaluate different renal proton density fat fraction (PDFF) analysis approaches. Additionally, we assessed renal fat in obese individuals and lean individuals. This was a retrospective observational case-control study. Twenty-eight obese individuals and 14 lean controls underwent MRI with multi-point Dixon technique for PDFF maps. The following renal PDFF image analysis approaches were performed and compared: (1) five circular regions of interest (ROIs) in six slices, (2) three circular ROIs in one slice, (3) freehand segmentation of renal parenchyma in one slice, and (4) freehand segmentation of renal parenchyma avoiding the renal border in one slice. Furthermore, renal PDFF was compared between obese and lean individuals. Methods 1, 2, and 4 were positively correlated (r ≥ 0.498, p ≤ 0.001). Renal PDFF values varied more with regards to ROI placement within slices than mean PDFF between slices. Using all methods, the obese individuals had significantly higher renal PDFF values compared with the lean controls. Renal PDFF should be measured covering large areas of the kidney while excluding artifacts. This can be achieved using multiple circular ROIs. Increased lipid accumulation in the kidneys was related to obesity.

Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants.

Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, transmembrane six superfamily member 2 (TM6SF2) rs58542926 and membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.

Intraindividual difference between supraclavicular and subcutaneous proton density fat fraction is associated with cold-induced thermogenesis

Brown adipose tissue (BAT) activity is triggered by cold exposure resulting in an increased resting energy expenditure, called cold-induced non-shivering thermogenesis (CIT). Magnetic resonance (MR)-based proton density fat fraction (PDFF) of the supraclavicular fossa has been proposed as a surrogate marker of human BAT. The present study investigates supraclavicular PDFF in relation to CIT. For this prospective cross-sectional study 39 adults were recruited, from a cross-sectional study, exploring energy expenditure after cold exposure compared to thermoneutral conditions. Participants underwent additional MR examination of neck, pelvis, and abdomen. Supraclavicular and subcutaneous gluteal adipose tissue depots were segmented semi-automatically. Mean PDFF was assessed for each compartment and the delta PDFF was calculated as the difference of both. Correlation analysis of supraclavicular PDFF to CIT was performed for the whole cohort and subgroups, sorted by body mass index (BMI) and body fat percentage. Median age of participants (61.5% female) was 27 years. BMI ranged from 19.0 to 38.5 kg/m2, with body fat percentages from 4.6% to 45.3%. Median supraclavicular PDFF of 82.5% and median gluteal PDFF of 91.1%, were significantly different (P<0.0001). Median delta PDFF was 8.8% (3.9-21.9%). Mean CIT was 4.7%±9.0%. No statistically significant correlation of supraclavicular PDFF and CIT was found in the whole cohort and in most of the observed subgroups. Just the subgroup with normal body fat percentage revealed significant correlations between supraclavicular PDFF and CIT (rho =-0.59; P=0.003). Delta PDFF was significantly associated with CIT (rho =0.36; P=0.026). PDFF is influenced by adiposity. Therefore, if supraclavicular PDFF is used as approach to indirectly assess BAT presence, body composition should be considered. Delta PDFF, as the difference between gluteal and supraclavicular PDFF, may be a marker of CIT.

Diagnostic performance of ultrasound hepatorenal index for the diagnosis of hepatic steatosis in children.

Non-alcoholic fatty liver disease (NAFLD) is increasing in prevalence and is the most common cause of pediatric chronic liver disease. Objective US-based measures of hepatic steatosis are an unmet clinical need. To evaluate the diagnostic performance of quantitative measurement of liver echogenicity (hepatorenal index, or HRI) for hepatic steatosis in a pediatric cohort. We identified pediatric patients (≤18years old) who underwent both clinically indicated abdominal US and MRI with liver proton-density fat fraction (PDFF) within the 3-month period during the timeframe of July 2015-April 2020 (n=69). Using ImageJ, we drew small circular regions of interest (ROIs) and large freehand ROIs in the liver and right kidney on single longitudinal and transverse images to measure echogenicity (arbitrary units). We calculated four HRIs (liver-to-kidney ratio) as well as liver histogram features. Five pediatric radiologists independently reported the qualitative presence/absence of hepatic steatosis. We used Pearson correlation (r) to assess associations and receiver operating characteristic (ROC) curve analyses to evaluate diagnostic performance. Multivariable logistic regression was used to further assess relationships. Mean patient age was 11.6 (standard deviation [SD] 4.7, range 0.3-18) years; 27/69 (39.1%) were female. Mean PDFF was 12.5% (SD 13.1%, range 1-48%); 34/69 (49.3%) patients were classified as having hepatic steatosis by MRI (PDFF ≥6%). There were significant, positive correlations between all four US HRI methods and PDFF (r=0.51-0.61); longitudinal freehand ROIs exhibited the strongest correlation (r=0.61; P<0.0001). Longitudinal freehand ROI HRI had moderate diagnostic performance for the binary presence of steatosis (area under the curve [AUC]=0.80, P<0.0001), with an optimal cut-off value >1.75 (sensitivity=70.6%, specificity=77.1%). Radiologists' sensitivity for detecting hepatic steatosis ranged from 79.4% to 97.1%, and specificity ranged from 91.2% to 100%. Significant multivariable predictors of PDFF ≥6% included HRI (P=0.002; odds ratio [OR]=34.2), body mass index (BMI) percentile (P=0.005; OR=1.06), and liver gray-scale echogenicity standard deviation (P=0.02; OR=0.79) (receiver operating characteristic AUC = 0.92). Quantitative US HRI has moderate diagnostic performance for detecting liver fat in children and positively correlates with MRI PDFF. Incorporation of BMI-percentile and gray-scale echogenicity standard deviation improved diagnostic performance.

Fat- and iron-corrected ADC to assess liver fibrosis in patients with chronic hepatitis B.

We aimed to evaluate the diagnostic performance of apparent diffusion coefficient (ADC) in assessing liver fibrosis after correcting for the effects of hepatic steatosis or iron deposition. Seventy-three patients with chronic hepatitis B (CHB) were included in this retrospective study. The aspartate aminotransferase-to-platelet ratio index (APRI) was calculated for classification of the fibrosis grade. Significant fibrosis and cirrhosis were diagnosed with the APRI. The proton density fat fraction (PDFF), R2*, and ADC values were measured. The impact of the PDFF and R2* on the ADC was analyzed. The PDFF- and R2*-corrected ADC values (ADCPDFF and ADCR2*) were calculated according to linear regression equations. The diagnostic performance of uncorrected ADC (ADCu), ADCPDFF and ADCR2* in predicting significant fibrosis and cirrhosis was assessed, and the area under the curve (AUC) values were compared. Among the 73 patients in this study, the mean ADC was 0.866 ± 0.084×10-3 mm2/s, the mean R2* was 60.24 (42.77, 85.37) 1/s, and the mean PDFF was 2.90% (1.60%- 4.80%). The ADC was negatively correlated with the PDFF (r= -0.298, P = .010) and R2* (r = -0.457, P < .001). Linear regression analysis showed that the PDFF and R2* were independent factors of the ADC (β= -0.315, P = .007, R2= 0.099 and β= -0.493, P < .001, R2= 0.243, respectively). Compared with the uncorrected ADC (r= -0.307, P = .022), the correlation between the ADCPDFF and fibrosis grade increased (r= -0.513, P < .001), and the correlation between the ADCR2* and fibrosis grade decreased (r=-0.168, P = .215). The AUC of the ADCPDFF was significantly larger than that of the ADCu in the diagnosis of significant fibrosis and cirrhosis, which increased from 0.68 to 0.81 (P = .003) for predicting significant fibrosis and from 0.75 to 0.84 (P = .009) for predicting cirrhosis. The AUCs for the ADCR2* in the diagnosis of significant fibrosis and cirrhosis were both lower than that for the uncorrected ADC (P = .206 and P = .109, respectively). After correcting for the effects of steatosis, the diagnostic performance of the ADC for signifi-cant fibrosis and cirrhosis increased. The ADC corrected for the effects of steatosis may be more reliable for identifying liver fibrosis.

Quantification of Fat Metaplasia in the Sacroiliac Joints of Patients With Axial Spondyloarthritis by Chemical Shift-Encoded MRI: A Diagnostic Trial.

ObjectiveTo study the diagnostic performance of chemical shift-encoded MRI (CSE-MRI) in the diagnosis of axial spondyloarthritis (axSpA).MethodsCSE-MRI images were acquired for consecutive patients complaining of back pain as well as healthy volunteers. Proton density fat fraction (PDFF) values were measured independently by two readers. Diagnostic performance of CSE-MRI was analyzed by sensitivity analysis and ROC curve analysis. Logistic regression analysis was employed to investigate the risk factors of extensive fat deposition in the SIJs.ResultsA total of 52 r-axSpA patients, 37 nr-axSpA patients, 24 non-SpA patients and 34 healthy volunteers were included. Mean PDFF values in the SIJs of patients with r-axSpA and nr-axSpA (72.7% and 64.5%) were significantly higher than non-SpA patients and healthy volunteers (56.0% and 57.6%) (p<0.001). By defining extensive fat deposition in the SIJs as ≥8 ROIs with PDFF values over 70%, its sensitivity and specificity in diagnosing axSpA reached 72.47% and 86.21%%. By joining bone marrow edema (BME) with ≥8 ROIs (PDFF>70%), 22 (24.71%) and 23 (25.84%) more axSpA patients were classified as SIJ MRI (+) by reader 1 and 2, but specificities decreased by 15.52% and 10.34%. Multivariate logistic regression analysis confirmed longer disease duration as the independent risk factor of extensive fat deposition in SIJs (OR=1.15, 95%CI[1.03, 1.32]), while bDMARDs medication was a protective factor (OR=0.15, 95%CI[0.04, 0.51]).ConclusionCSE-MRI is a reliable tool to quantitively assess the fat metaplasia in the SIJs of axSpA patients. Extensive fat deposition in the SIJs could add incremental diagnostic value to BME, but at the cost of decreased specificities.

Texture Analysis Using CT and Chemical Shift Encoding-Based Water-Fat MRI Can Improve Differentiation Between Patients With and Without Osteoporotic Vertebral Fractures.

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<0.001). For the model with integral vBMD as the dependent variable, T2* combined with three PDFF-based texture features explained 40% of the variance (adjusted R2 = 0.40; p<0.001). Furthermore, regarding the differentiation between patients with and without osteoporotic vertebral fractures, a model including texture features from CT and CSE-MRI data showed better performance than a model based on integral vBMD and PDFF only ( = 0.47 vs. = 0.81; included texture features in the final model: integral vBMD, CT_Short-run_emphasis, CT_Varianceglobal, and PDFF_Variance).ConclusionUsing texture analysis for spine CT and CSE-MRI can facilitate the differentiation between patients with and without osteoporotic vertebral fractures, implicating that future fracture prediction in osteoporosis may be improved.

Proton Density Fat Fraction Spine MRI for Differentiation of Erosive Vertebral Endplate Degeneration and Infectious Spondylitis

Vertebral Modic type 1 (MT1) degeneration may mimic infectious disease on conventional spine magnetic resonance imaging (MRI), potentially leading to additional costly and invasive investigations. This study evaluated the diagnostic performance of the proton density fat fraction (PDFF) for distinguishing MT1 degenerative endplate changes from infectious spondylitis. A total of 31 and 22 patients with equivocal diagnosis of MT1 degeneration and infectious spondylitis, respectively, were retrospectively enrolled in this IRB-approved retrospective study and examined with a chemical-shift encoding (CSE)-based water-fat 3D six-echo modified Dixon sequence in addition to routine clinical spine MRI. Diagnostic reference standard was established according to histopathology or clinical and imaging follow-up. Intravertebral PDFF [%] and PDFFratio (i.e., vertebral endplate PDFF/normal vertebrae PDFF) were calculated voxel-wise within the single most prominent edematous bone marrow lesion per patient and examined for differences between MT1 degeneration and infectious spondylitis. Mean PDFF and PDFFratio of infectious spondylitis were significantly lower compared to MT1 degenerative changes (mean PDFF, 4.28 ± 3.12% vs. 35.29 ± 17.15% [p < 0.001]; PDFFratio, 0.09 ± 0.06 vs. 0.67 ± 0.37 [p < 0.001]). The areas under the curve (AUC) and diagnostic accuracies were 0.977 (p < 0.001) and 98.1% (cut-off at 12.9%) for PDFF and 0.971 (p < 0.001) and 98.1% (cut-off at 0.27) for PDFFratio. Our data suggest that quantitative evaluation of vertebral PDFF can provide a high diagnostic accuracy for differentiating erosive MT1 endplate changes from infectious spondylitis.

Association of Cervical and Lumbar Paraspinal Muscle Composition Using Texture Analysis of MR-Based Proton Density Fat Fraction Maps.

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.

MR-based proton density fat fraction (PDFF) of the vertebral bone marrow differentiates between patients with and without osteoporotic vertebral fractures

SummaryThe bone marrow proton density fat fraction (PDFF) assessed with MRI enables the differentiation between osteoporotic/osteopenic patients with and without vertebral fractures. Therefore, PDFF may be a potentially useful biomarker for bone fragility assessment.IntroductionTo evaluate whether magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) of vertebral bone marrow can differentiate between osteoporotic/osteopenic patients with and without vertebral fractures.MethodsOf the 52 study patients, 32 presented with vertebral fractures of the lumbar spine (66.4 ± 14.4 years, 62.5% women; acute low-energy osteoporotic/osteopenic vertebral fractures, N = 25; acute high-energy traumatic vertebral fractures, N = 7). These patients were frequency matched for age and sex to patients without vertebral fractures (N = 20, 69.3 ± 10.1 years, 70.0% women). Trabecular bone mineral density (BMD) values were derived from quantitative computed tomography. Chemical shift encoding-based water-fat MRI of the lumbar spine was performed, and PDFF maps were calculated. Associations between fracture status and PDFF were assessed using multivariable linear regression models.ResultsOver all patients, mean PDFF and trabecular BMD correlated significantly (r = − 0.51, P < 0.001). In the osteoporotic/osteopenic group, those patients with osteoporotic/osteopenic fractures had a significantly higher PDFF than those without osteoporotic fractures after adjusting for age, sex, weight, height, and trabecular BMD (adjusted mean difference [95% confidence interval], 20.8% [10.4%, 30.7%]; P < 0.001), although trabecular BMD values showed no significant difference between the subgroups (P = 0.63). For the differentiation of patients with and without vertebral fractures in the osteoporotic/osteopenic subgroup using mean PDFF, an area under the receiver operating characteristic (ROC) curve (AUC) of 0.88 (P = 0.006) was assessed. When evaluating all patients with vertebral fractures, those with high-energy traumatic fractures had a significantly lower PDFF than those with low-energy osteoporotic/osteopenic vertebral fractures (P < 0.001).ConclusionMR-based PDFF enables the differentiation between osteoporotic/osteopenic patients with and without vertebral fractures, suggesting the use of PDFF as a potential biomarker for bone fragility.

Quantitative Muscle MRI in Patients with Neuromuscular Diseases-Association of Muscle Proton Density Fat Fraction with Semi-Quantitative Grading of Fatty Infiltration and Muscle Strength at the Thigh Region.

(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.

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.

Diagnostic Accuracy of Quantitative Imaging Biomarkers in the Differentiation of Benign and Malignant Vertebral Lesions

PurposeTo compare and combine the diagnostic performance of the apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) and proton density fat fraction (PDFF) derived from chemical-shift encoding (CSE)-based water-fat magnetic resonance imaging (MRI) for distinguishing benign and malignant vertebral bone marrow lesions (VBML).MethodsA total of 55 consecutive patients with 53 benign (traumatic, inflammatory and primary) and 36 malignant (metastatic and hematologic) previously untreated VBMLs were prospectively enrolled in this IRB-approved study and underwent sagittal DWI (single-shot spin-echo echo-planar with multi-slice short TI inversion recovery fat suppression) and CSE-based MRI (gradient-echo 6‑point modified Dixon) in addition to routine clinical spine MRI at 1.5 T or 3.0 T. Diagnostic reference standard was established according to histopathology or imaging follow-up. The ADC = ADC (0, 800) and PDFF = fat / (water + fat) were calculated voxel-wise and examined for differences between benign and malignant lesions.ResultsThe ADC and PDFF values of malignant lesions were significantly lower compared to benign lesions (mean ADC 861 × 10−6 mm2/s vs. 1323 × 10−6 mm2/s, p < 0.001; mean PDFF 3.1% vs. 28.2%, p < 0.001). The areas under the curve (AUC) and diagnostic accuracies were 0.847 (p < 0.001) and 85.4% (cut-off at 1084.4 × 10−6 mm2/s) for ADC and 0.940 (p < 0.001) and 89.9% for PDFF (cut-off at 7.8%), respectively. The combined use of ADC and PDFF improved the diagnostic accuracy to 96.6% (malignancy if ADC ≤ 1118.2 × 10−6 mm2/s and PDFF ≤ 20.0%, otherwise benign).ConclusionQuantitative evaluation of both ADC and PDFF was useful in differentiating benign VBMLs from malignancy. The combination of ADC and PDFF improved the diagnostic performance and yielded high diagnostic accuracy for the differentiation of benign and malignant VBMLs.

Repeatability and accuracy of various region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification.

To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF. This was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly ("balanced") were compared with those that did not ("unbalanced") using two-sample t tests. The 29 enrolled subjects (23 male, mean age 24years) had mean 9-ROI PDFF 11.8% (1.1-36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC < 1%, 50 (83%) achieved inter-exam RC < 1%, and all (100%) achieved MAE < 1%. Balanced sampling strategies had higher ICCs and lower RCs, and lower MAEs than unbalanced strategies in aggregate (p < 0.001 for comparisons between balanced vs. unbalanced strategies). Repeatability improves and error diminishes with more ROIs. Balanced 4-ROI strategies provide high repeatability and low error.