Role of Advanced MRI Techniques in the Quantitative Assessment of Liver Fat—A Multimodality-Based Comparative Study of Diagnostic Performance in a Tertiary Care Institute

Objective To evaluate the accuracy of noninvasive imaging methods including gray-scale ultrasound, ultrasound shear wave elastography, unenhanced computed tomography (CT), and proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) using three-dimensional (3D) multiecho multipoint chemical shift–encoded spoiled gradient echo (q-DIXON) sequence in the quantification of hepatic steatosis, with proton MR spectroscopy (H1-MRS) as the reference standard in Indian population. Methods Our study included 100 consecutive adult patients referred to the department of radiology in our hospital for imaging of liver. Fat content of liver was recorded using MRI (H1-MRS and q-DIXON), unenhanced CT (average liver attenuation [ALI] and liver attenuation index [LAI]) and ultrasonography (USG) (gray-scale grading and shear wave elastography [SWE]). Data were analyzed by linear regression and Bland–Altman analysis for each technique compared with H1-MRS. The diagnostic performances of all the methods were compared using DeLong test, for detection of mild and moderate-to-severe hepatic steatosis, separately. Results MRI q-DIXON PDFF showed excellent correlation (r = 0.917, r2 = 0.840) and strong agreement (1.48 ±3.01) with H1-MRS-derived PDFF measurements. Unenhanced CT-based methods showed moderate correlation with modest agreement (r = −0.826, r2 = 0.681, −40.18 ± 16.05 for ALI and r = −0.858, r2 = 0.735, 13.4 ± 15.3 for LAI) whereas USG gray-scale assessment showed low correlation (weighted Kappa value 0.366) with H1-MRS PDFF. No correlation was found between USG-SWE results and PDFF measured with H1-MRS. Comparison of areas under curve (AUCs) using DeLong test revealed that MRI q-DIXON method performed the best for diagnosis of hepatic steatosis compared with rest. For moderate to severe steatosis, MRI q-DIXON and unenhanced CT-based methods had comparable diagnostic performance with AUCs not showing statistically significant differences. Conclusion MRI q-DIXON shows strongest correlation with MRS and should be preferred for estimation of hepatic fat, especially when MRS is not available. Unenhanced CT shows limited diagnostic performance in detecting mild steatosis; however, it certainly has a role in diagnosing moderate-to-severe hepatic steatosis, such as evaluating donor candidates for living donor liver transplantation. USG, using both the traditional four-grade visual assessment and elastography in the present form, appears to have limited role in liver fat quantification.

Epicardial and pericardial adiposity without myocardial steatosis in Cushing’s syndrome

Context Cardiovascular disease is the leading cause of death in patients with Cushing’s syndrome. Cortisol excess and adverse metabolic profile could increase cardiac fat, which can subsequently impair cardiac structure and function. Objective We aimed to evaluate cardiac fat mass and distribution in patients with Cushing’s syndrome. Design In this prospective cross-sectional study 23 patients with Cushing’s syndrome and 27 control subjects of comparable age, sex and body-mass-index were investigated by cardiac magnetic resonance imaging and proton spectroscopy. Patients were explored before and after biochemical disease remission. Outcome measures Myocardial fat measured by the Dixon method was the main outcome measure. The intramyocardial triglyceride/water ratio measured by spectroscopy and epicardial and pericardial fat volumes were secondary outcome measures. Results No difference was found between patients and controls in intramyocardial lipid content. Epicardial fat mass was increased in patients compared to controls (30.8g/m 2 [20.4;34.8] vs 17.2g/m 2 [13.1;23.5], p<0.0001). Similarly, pericardial fat mass was increased in patients compared to controls (28.3g/m 2 [17.9;38.0] vs 11.4g/m 2 [7.5;19.4], p=0.0035). Sex, HbA1c and presence of hypercortisolism were independent determinants of epicardial fat. Pericardial fat was associated with sex, impaired glucose homeostasis and left ventricular wall thickness. Disease remission decreased epicardial fat mass without affecting pericardial fat. Conclusions Intramyocardial fat stores are not increased in patients with Cushing’s syndrome, despite highly prevalent metabolic syndrome, suggesting increased cortisol-mediated lipid consumption. Cushing’s syndrome is associated with marked accumulation of epicardial and pericardial fat. Epicardial adiposity may exert paracrine proinflammatory effects promoting cardiomyopathy. Trial registration ClinicalTrials.gov, NCT02202902.

Free-breathing non-contrast flow-independent cardiovascular magnetic resonance angiography using cardiac gated, magnetization-prepared 3D Dixon method: assessment of thoracic vasculature in congenital heart disease

Background To evaluate a non-contrast respiratory- and electrocardiogram-gated 3D cardiovascular magnetic resonance angiography (CMRA) based on magnetization-prepared Dixon method (relaxation-enhanced angiography without contrast and triggering, REACT) for the assessment of the thoracic vasculature in congenital heart disease (CHD) patients. Methods 70 patients with CHD (mean 28 years, range: 10–65 years) were retrospectively identified in this single-center study. REACT-CMRA was applied with respiratory- and cardiac-gating. Image quality (IQ) of REACT-CMRA was compared to standard non-gated multi-phase first-pass-CMRA and respiratory- and electrocardiogram-gated steady-state-CMRA. IQ of different vessels of interest (ascending aorta, left pulmonary artery, left superior pulmonary vein, right coronary ostium, coronary sinus) was independently assessed by two readers on a five-point Likert scale. Measurements of vessel diameters were performed in predefined anatomic landmarks (ascending aorta, left pulmonary artery, left superior pulmonary vein). Both readers assessed artifacts and vascular abnormalities. Friedman test, chi-squared test, and Bland-Altman method were used for statistical analysis. Results Overall IQ score of REACT-CMRA was higher compared to first-pass-CMRA (3.5 ± 0.4 vs. 2.7 ± 0.4, P < 0.001) and did not differ from steady-state-CMRA (3.5 ± 0.4 vs. 3.5 ± 0.6, P = 0.99). Non-diagnostic IQ of the defined vessels of interest was observed less frequently on REACT-CMRA (1.7 %) compared to steady-state- (4.3 %, P = 0.046) or first-pass-CMRA (20.9 %, P < 0.001). Close agreements in vessel diameter measurements were observed between REACT-CMRA and steady-state-CMRA (e.g. ascending aorta, bias: 0.38 ± 1.0 mm, 95 % limits of agreement (LOA): − 1.62–2.38 mm). REACT-CMRA showed high intra- (bias: 0.04 ± 1.0 mm, 95 % LOA: − 1.9–2.0 mm) and interobserver (bias: 0.20 ± 1.1 mm, 95 % LOA: − 2.0–2.4 mm) agreements regarding vessel diameter measurements. Fat-water separation artifacts were observed in 11/70 (16 %) patients on REACT-CMRA but did not limit diagnostic utility. Six vascular abnormalities were detected on REACT-CMRA that were not seen on standard contrast-enhanced CMRA. Conclusions Non-contrast-enhanced cardiac-gated REACT-CMRA offers a high diagnostic quality for assessment of the thoracic vasculature in CHD patients.

Can Achilles tendon xanthoma be distinguished from Achilles tendinopathy using Dixon method MRI? A cross-sectional exploratory study

Background Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons. Methods Bilateral MRI scans of Achilles tendons from 30 participants (n = 10 Achilles tendon xanthoma, n = 10 Achilles overuse tendinopathy, n = 10 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness. Results Fat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p < 0.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p = 0.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p < 0.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p < 0.01 and p < 0.001, respectively). Conclusion MRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.

Assessment of bone marrow fat fractions in the mandibular condyle head using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method

The prevalence of temporomandibular joint disorder (TMD) is gradually increasing, and magnetic resonance imaging (MRI) is becoming increasingly common as a modality used to diagnose TMD. Edema and osteonecrosis in the bone marrow of the mandibular condyle have been considered to be precursors of osteoarthritis, but these changes are not evaluated accurately and quantitatively on routine MRI. The iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method, as a cutting-edge MRI technique, can separate fat and water using three asymmetric echo times and the three-point Dixon method. The purpose of this study was to analyze the quantitative fat fraction (FF) in the mandibular condyle head using the IDEAL-IQ method. Seventy-nine people who underwent MRI using IDEAL-IQ were investigated and divided into 1) the control group, without TMD symptoms, and 2) the TMD group, with unilateral temporomandibular joint (TMJ) pain. In both groups, the FF of the condyle head in the TMJ was analyzed by two oral and maxillofacial radiologists. In the TMD group, 29 people underwent cone-beam computed tomography (CBCT) and the presence or absence of bony changes in the condylar head was evaluated. The FF measurements of the condyle head using IDEAL-IQ showed excellent inter-observer and intra-observer agreement. The average FF of the TMD group was significantly lower than that of the control group (p < 0.05). In the TMD group, the average FF values of joints with pain and joints with bony changes were significantly lower than those of joints without pain or bony changes, respectively (p < 0.05). The FF using IDEAL-IQ in the TMJ can be helpful for the quantitative diagnosis of TMD.

Evaluation of SUVlean consistency in FDG and PSMA PET/MR with Dixon-, James-, and Janma-based lean body mass correction

Purpose To systematically evaluate the consistency of various standardized uptake value (SUV) lean body mass (LBM) normalization methods in a clinical positron emission tomography/magnetic resonance imaging (PET/MR) setting. Methods SUV of brain, liver, prostate, parotid, blood, and muscle were measured in 90 18F-FDG and 28 18F-PSMA PET/MR scans and corrected for LBM using the James, Janma (short for Janmahasatian), and Dixon approaches. The prospective study was performed from December 2018 to August 2020 at Shanghai East Hospital. Forty dual energy X-ray absorptiometry (DXA) measurements of non-fat mass were used as the reference standard. Agreement between different LBM methods was assessed by linear regression and Bland-Altman statistics. SUV’s dependency on BMI was evaluated by means of linear regression and Pearson correlation. Results Compared to DXA, the Dixon approach presented the least bias in LBM/weight% than James and Janma models (bias 0.4±7.3%, − 8.0±9.4%, and − 3.3±8.3% respectively). SUV normalized by body weight (SUVbw) was positively correlated with body mass index (BMI) for both FDG (e.g., liver: r = 0.45, p < 0.001) and PSMA scans (r = 0.20, p = 0.31), while SUV normalized by lean body mass (SUVlean) revealed a decreased dependency on BMI (r = 0.22, 0.08, 0.14, p = 0.04, 0.46, 0.18 for Dixon, James, and Janma models, respectively). The liver SUVbw of obese/overweight patients was significantly larger (p < 0.001) than that of normal patients, whereas the bias was mostly eliminated in SUVlean. One-way ANOVA showed significant difference (p < 0.001) between SUVlean in major organs measured using Dixon method vs James and Janma models. Conclusion Significant systematic variation was found using different approaches to calculate SUVlean. A consistent correction method should be applied for serial PET/MR scans. The Dixon method provides the most accurate measure of LBM, yielding the least bias of all approaches when compared to DXA.

Evaluation of SUVlean Consistency in FDG and PSMA PET/MR with Dixon, James and Janma Based Lean Body Mass Correction

PurposeTo systematically evaluate the consistency of various standardized uptake value (SUV) lean body mass (LBM) normalization methods in a clinical positron emission tomography/magnetic resonance imaging (PET/MR) setting.MethodsSUV of brain, liver, prostate, parotid, blood and muscle were measured in 90 18F-FDG and 28 18F-PSMA PET/MR scans and corrected for LBM using the James, Janma (short for Janmahasatian) and Dixon models. 40 dual energy X-ray absorptiometry (DXA) measurements of non-fat mass were used as the reference standard. Agreement between different methods was assessed by linear regression and Bland-Altman statistics. ResultsLBM fraction measured by DXA, James, Janma and Dixon approaches was 68.19±6.43%, 66.95±6.71%, 76.20±5.41% and 71.56±7.97% respectively. Compared to DXA, the Dixon approach presented the minimal bias when compared to the James and Janma models (bias: 0.76±7.35, -8.01±9.36, -3.33±8.26 respectively). SUV normalized by bodyweight (SUVbw) was positively correlated with Body Mass Index (BMI) in both FDG (liver: r=0.454, p<0.001) and PSMA studies (r=0.197,p=0.31), while SUV normalized by lean body mass (SUVlean) revealed a decreased dependency on BMI (r=0.22,0.08,0.14, p=0.04,0.46,0.18 for Dixon, James and Janma models respectively). Paired T-test showed significant difference between SUVlean of major organs measured using Dixon method vs James and Janma models.ConclusionSignificant systematic variation was found among SUVlean calculated using different approaches. A consistent correction method should be applied in PET/MR serial scans.

OP0326 ACPA-INDUCED PAIN-BEHAVIOR, BONE LOSS AND TENDON INFLAMMATION IN MICE: A NOVEL MODEL FOR THE PRE-DISEASE PHASES OF ACPA-POSITIVE RHEUMATOID ARTHRITIS

Background:In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPAs) are associated with bone loss and pain. Recently, tenosynovitis has been suggested as a predicting factor for arthritis progression in individuals at-risk for RA.Objectives:We aimed to investigate if transfer of human ACPAs into mice could induce tenosynovitis and/or subclinical inflammation.Methods:Monoclonal ACPA (1325:04C03 and 1325:01B09) and control (1362:01E02) antibodies (mAbs) were generated from synovial plasma or memory B cells of RA patients. 2mg of combination of monoclonal ACPAs or control antibody were injected in BALB/c female mice (age 12-16 weeks) (n= 9). Pain-like behavior was monitored by measuring mechanical hypersensitivity using von Frey filaments every 3 days and estimation by up-down Dixon method. Bone morphometrics was analyzed by micro-CT. Using specially designed mobilization casts, dedicated mouse MRI coils, and gadolinium enhanced contrast medium, the hind limbs of these mice were scanned in a 9.4 T scanner and resulting T1-weighted images were evaluated for signs of soft tissue joint inflammation. The MRI images were scored for the presence of joint involvement and tendon inflammatory changes by 3 readers in a blinded manner.Figure 1.NAPA performed on healthy donor mo-DCs incubated with native, PAD2-citrullinated, and PAD4-citrullinated fibrinogen. Alpha, beta, and gamma chains of fibrinogen are shown separately. Each colored line represents a unique peptide. Nested peptides with a common core motif are shown in the same color. Grey bar denotes peptides with identical core motif between samples.Results:ACPAs (1325:04C03 and 1325:01B09) induced pain-like behavior (lasting for at least 4 weeks) and reduction of the trabecular and cortical bone thickness in the hind limbs as compared to control monoclonal antibodies (p<0.05). While no macroscopic or MRI signs of synovial inflammation were detected, MRI subclinical inflammation of the tendon sheaths was present in mice injected with ACPAs, but not in those injected with control mAb. Semi-quantitative scoring of the inflammatory tendon changes showed significant higher values in mice injected with ACPA (median of 1, range 0 to 2) than those injected with control mAb (median of 0, range 0 to 1).Conclusion:We show that ACPA induces pain-like behavior, bone loss and tendon sheath inflammation in mice, a model that mimics the preclinical state of ACPA positive RA.References:[1]Harre, U. et al. J Clin Invest (2012)[2]Krishnamurthy, A. et al. Ann Rheum Dis (2016, 2019), JI 2019[3]Wigerblad, G. et al. Ann Rheum Dis (2016, 2019)[4]KleyerA, Seminars in Arthritis and Rheumatism (2016)Disclosure of Interests:Akilan Krishnamurthy: None declared, Yogan Kisten: None declared, Alexandra Circiumaru: None declared, Koji Sakurabas: None declared, Patrik Jarvolli: None declared, Juan Jimenez Jimenez Andrade: None declared, Peter Damberg: None declared, Heidi Wähämaa: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica, Lars Klareskog: None declared, Camilla Svensson: None declared, Bence Réthi: None declared, Anca Catrina: None declared

THU0533 A SINGLE MRI DIXON SEQUENCE TO ASSESS DISEASE ACTIVITY AND CARTILAGE IN EARLY RHEUMATOID HANDS: ONE SEQUENCE TO ASSESS THEM ALL?

Background:OMERACT recommends three “core set” MRI sequences with an optional cartilage-dedicated sequence to perform Rheumatoid Arthritis (RA) MRI scoring (RAMRIS) (1). Dixon method allows the production of four different images from a single MRI sequence.Objectives:To test a short MRI protocol based on a single Dixon sequence to assess disease activity and cartilage in hands of patients with early RA.Methods:Twenty-four patients (16 women, mean age 45.7 years old) with early DMARD-naive RA meeting the ACR/EULAR 2010 criteria were prospectively included. Both hands of each patient were imaged with MRI including contrast-enhanced T1-weighted Dixon and OMERACT “core set” MRI sequences and with conventional radiography.Two musculoskeletal radiologists (R1 and R2) separately assessed disease activity according to RAMRIS scoring system based on the Dixon images (contrast-enhanced T1-weighted Dixon water-only images to score synovitis, tenosynovitis and osteitis and contrast-enhanced T1-weighted Dixon fat-only images to score erosions) and the three OMERACT “core set” MRI sequences (contrast-enhanced fat-saturated T1-weighted images to score synovitis and tenosynovitis, fat-saturated T2-weighted images to score osteitis and T1-weighted images without contrast-material injection to score erosions).One radiologist (R1) separately measured the thickness of the cartilage in the joints corresponding to those assessed by the Sharp/van der Heijde modified scoring method on contrast-enhanced T1-weighted Dixon out-of-phase images and radiographs (2).RAMRIS scoring and measurement of the cartilage thickness were repeated by R1 to assess intra-observer agreement. Statistical analysis was based on intra-class correlation coefficients (ICC) with 95% confidence interval to assess inter-technique, intra-observer and inter-observer agreement. The strength of agreement was interpreted as follows: ≤0, poor; 0.01-0.20, slight; 0.21-0.40, fair; 0.41-0.60, moderate; 0.61-0.80, substantial and ≥0.81, excellent.Results:Agreement between total RAMRIS scores obtained with the Dixon water- and fat-only images and total RAMRIS scores obtained with the OMERACT sequences was excellent for R1 (0.94; 0.86-0.97) and R2 (0.91; 0.81-0.96). Intra-observer agreement was excellent with Dixon images (0.97; 0.92-0.98) and OMERACT sequences (0.96; 0.90-0.98). Inter-observer agreement was excellent with Dixon images (0.92; 0.82-0.96) and OMERACT sequences (0.93; 0.85-0.97).Agreement between the measures of cartilage thickness on the Dixon out-of-phase images and the measures of cartilage thickness on radiographs was substantial (0.71; 0.66-0.75). Intra-observer agreement was excellent with Dixon out-of-phase images (0.94; 0.93-0.95) and radiographs (0.93; 0.92-0.94).Conclusion:An MRI protocol based on a single contrast-enhanced T1-weighted Dixon sequence allows reproducible RAMRIS scoring and measurement of the cartilage thickness. Further studies should be performed to evaluate the value of a short MRI protocol based on the Dixon method to monitor disease activity including cartilage loss in treated RA patients.References:[1]Ostergaard M, Peterfy CG, Bird P, Gandjbakhch F, Glinatsi D, Eshed I, et al. The OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging (MRI) Scoring System: Updated Recommendations by the OMERACT MRI in Arthritis Working Group. J Rheumatol. 2017;44(11):1706-12.[2]van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 1999;26(3):743-5.Disclosure of Interests:Thomas Kirchgesner: None declared, Maria Stoenoiu: None declared, Nicolas Michoux: None declared, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Bruno Vande Berg: None declared