A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis.

OBJECTIVES: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. METHODS: The proposed system utilises post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0-2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema.This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet's agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. RESULTS: The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1-3 were 80-90% and 75-90% respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. CONCLUSION: The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA.

Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis.

OBJECTIVES: To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. METHODS: YP aged 14-24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (≥1 inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. RESULTS: Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) patients with JIA vs 15% (2/13) controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in ≥ 1 clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients). CONCLUSIONS: WBMRI's validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications.

Weight-loss Independent Clinical and Metabolic Biomarkers Associated with Type 2 Diabetes Remission Post-bariatric/metabolic Surgery.

PURPOSE: Remission of type 2 diabetes (T2D) can be achieved by many, but not all, people following bariatric/metabolic surgery. The mechanisms underlying T2D remission remain incompletely understood. This observational study aimed to identify novel weight-loss independent clinical, metabolic and genetic factors that associate with T2D remission using comprehensive phenotyping. MATERIALS AND METHODS: Ten patients without T2D remission (non-remitters) were matched to 10 patients with T2D remission (remitters) for age, sex, type of surgery, body weight, BMI, post-operative weight loss, duration from surgery and duration of T2D. Detailed body composition assessed using magnetic resonance imaging, gut hormones, serum metabolomics, insulin sensitivity, and genetic risk scores for T2D and anthropometric traits were assessed. RESULTS: Remitters had significantly greater ß-cell function and circulating acyl ghrelin levels, but lower visceral adipose tissue (VAT): subcutaneous adipose tissue (SAT) ratio than non-remitters. Branched-chain amino acids (BCAAs) and VLDL particle size were the most discriminant metabolites between groups. A significant positive correlation between, VAT area, VAT:SAT ratio and circulating levels of BCAAs was observed, whereas a significant negative correlation between BCAAs and ß-cell function was revealed. CONCLUSION: We highlight a potentially novel relationship between VAT and BCAAs, which may play a role in glucoregulatory control. Improvement in ß-cell function, and the role ghrelin plays in its recovery, is likely another key factor influencing T2D remission post-surgery. These findings suggest that adjunctive approaches that target VAT loss and restoration of BCAA metabolism might achieve higher rates of long-term T2D remission post-surgery.

Measuring response to treatment in axial spondyloarthritis using quantitative imaging biomarkers: a prospective observational cohort study.

OBJECTIVE: Objective assessments of disease activity and response to treatment in axial spondyloarthritis (axSpA) remain a challenge; quantitative imaging biomarkers (QIBs) of inflammation could enhance assessments of disease activity and therapeutic response. We aimed to determine the responsiveness of QIBs obtained from diffusion-weighted imaging (DW-MRI) and chemical shift-encoded MRI (CSE-MRI) using the partially automated Bone Edema and Adiposity Characterisation with Histograms (BEACH) software tool in axSpA patients undergoing biologic therapy. METHODS: We conducted a prospective longitudinal cohort study, including 30 patients with axSpA undergoing biologic therapy. Patients were scanned before and after biologic therapy using conventional MRI, DWI and CSE-MRI at 3T. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) were assessed using the BEACH tool (https://github.com/TJPBray/BEACH), and conventional MR images were assessed using established visual scoring methods by expert radiologists. Responsiveness - the ability of the MRI measurements to capture changes in disease occurring as a result of biologic therapy - was assessed using the standardized response mean (SRM). Inter-reader reliability of the ADC and PDFF maps was assessed using Bland-Altman limits of agreement analysis and the intraclass correlation coefficient. RESULTS: Responsiveness to therapy was moderate for ADC-based parameters (SRM 0.50) and comparable to established visual scoring methods for bone marrow oedema (SRM 0.53). Interobserver variability was lower for QIBs compared with conventional visual scores methods. CONCLUSIONS: QIBs measured using the BEACH tool are sensitive to changes in inflammation in axSpA following biologic therapy, with similar responsiveness and lower interobserver variability to visual scoring by expert radiologists. ADVANCES IN KNOWLEDGE: QIBs measured using the partially automated BEACH tool offer an objective measure of response to biologic therapy in axSpA.

A multiparametric alternative to short inversion-time inversion recovery for imaging inflammation: T2water and fat fraction measurement using chemical shift-encoded turbo spin-echo MRI.

PURPOSE: Short-inversion-time inversion-recovery MRI is used widely for imaging bone and soft-tissue inflammation in rheumatic inflammatory diseases, but there is no widely available quantitative equivalent of this sequence. This limits our ability to objectively assess inflammation and distinguish it from other processes. To address this, we investigate the use of the widely available Dixon turbo spin echo (TSE Dixon) sequence as a practical approach to simultaneous water-specific T2 (T2water ) and fat fraction (FF) measurement. METHODS: We use a series of TSE Dixon acquisitions with varying effective TEs (TEeff ) to quantify T2water and FF. The validity of this approach is assessed in a series of phantom and in vivo experiments, with reference values provided by Carr-Purcell-Meiboom-Gill acquisitions, MRS, and phantoms. The effect of inflammation on parameter values is evaluated in patients with spondyloarthritis. RESULTS: The T2water estimates obtained from TSE Dixon were accurate compared with the reference values from Carr-Purcell-Meiboom-Gill and spectroscopy in both fat-free environments and in the presence of fat. FF measurements with T2water correction from TSE Dixon were accurate from 0% to 60% FF and were not confounded by T2water variations. In vivo imaging produced good quality images that were artifact free, produced plausible T2 values, separating and quantifying the effect of inflammation on T2water and FF. CONCLUSION: The T2water and FF measurements based on TSE Dixon with effective TE increments are accurate over a range of T2 and FF values and could provide a widely available quantitative alternative to the short-inversion-time inversion-recovery sequence for imaging inflamed tissue.

Volume of hyperintense inflammation (VHI): A quantitative imaging biomarker of inflammation load in spondyloarthritis, enabled by human-machine cooperation.

Qualitative visual assessment of MRI scans is a key mechanism by which inflammation is assessed in clinical practice. For example, in axial spondyloarthritis (axSpA), visual assessment focuses on the identification of regions with increased signal in the bone marrow, known as bone marrow oedema (BMO), on water-sensitive images. The identification of BMO has an important role in the diagnosis, quantification and monitoring of disease in axSpA. However, BMO evaluation depends heavily on the experience and expertise of the image reader, creating substantial imprecision. Deep learning-based segmentation is a natural approach to addressing this imprecision, but purely automated solutions require large training sets that are not currently available, and deep learning solutions with limited data may not be sufficiently trustworthy for use in clinical practice. To address this, we propose a workflow for inflammation segmentation incorporating both deep learning and human input. With this 'human-machine cooperation' workflow, a preliminary segmentation is generated automatically by deep learning; a human reader then 'cleans' the segmentation by removing extraneous segmented voxels. The final cleaned segmentation defines the volume of hyperintense inflammation (VHI), which is proposed as a quantitative imaging biomarker (QIB) of inflammation load in axSpA. We implemented and evaluated the proposed human-machine workflow in a cohort of 29 patients with axSpA who had undergone prospective MRI scans before and after starting biologic therapy. The performance of the workflow was compared against purely visual assessment in terms of inter-observer/inter-method segmentation overlap, inter-observer agreement and assessment of response to biologic therapy. The human-machine workflow showed superior inter-observer segmentation overlap than purely manual segmentation (Dice score 0.84 versus 0.56). VHI measurements produced by the workflow showed similar or better inter-observer agreement than visual scoring, with similar response assessments. We conclude that the proposed human-machine workflow offers a mechanism to improve the consistency of inflammation assessment, and that VHI could be a valuable QIB of inflammation load in axSpA, as well as offering an exemplar of human-machine cooperation more broadly.

Quantitative magnetic resonance imaging (qMRI) in axial spondyloarthritis.

Imaging, and particularly MRI, plays a crucial role in the assessment of inflammation in rheumatic disease, and forms a core component of the diagnostic pathway in axial spondyloarthritis. However, conventional imaging techniques are limited by image contrast being non-specific to inflammation and a reliance on subjective, qualitative reader interpretation. Quantitative MRI methods offer scope to address these limitations and improve our ability to accurately and precisely detect and characterise inflammation, potentially facilitating a more personalised approach to management. Here, we review quantitative MRI methods and emerging quantitative imaging biomarkers for imaging inflammation in axial spondyloarthritis. We discuss the potential benefits as well as the practical considerations that must be addressed in the movement toward clinical translation of quantitative imaging biomarkers.

MAGORINO: Magnitude-only fat fraction and R* 2 estimation with Rician noise modeling.

PURPOSE: Magnitude-based fitting of chemical shift-encoded data enables proton density fat fraction (PDFF) and R 2 * $$ {R}_2^{\ast } $$ estimation where complex-based methods fail or when phase data are inaccessible or unreliable. However, traditional magnitude-based fitting algorithms do not account for Rician noise, creating a source of bias. To address these issues, we propose an algorithm for magnitude-only PDFF and R 2 * $$ {R}_2^{\ast } $$ estimation with Rician noise modeling (MAGORINO). METHODS: Simulations of multi-echo gradient-echo signal intensities are used to investigate the performance and behavior of MAGORINO over the space of clinically plausible PDFF, R 2 * $$ {R}_2^{\ast } $$ , and SNR values. Fitting performance is assessed through detailed simulation, including likelihood function visualization, and in a multisite, multivendor, and multi-field-strength phantom data set and in vivo. RESULTS: Simulations show that Rician noise-based magnitude fitting outperforms existing Gaussian noise-based fitting and reveals two key mechanisms underpinning the observed improvement. First, the likelihood functions exhibit two local optima; Rician noise modeling increases the chance that the global optimum corresponds to the ground truth. Second, when the global optimum corresponds to ground truth for both noise models, the optimum from Rician noise modeling is closer to ground truth. Multisite phantom experiments show good agreement of MAGORINO PDFF with reference values, and in vivo experiments replicate the performance benefits observed in simulation. CONCLUSION: The MAGORINO algorithm reduces Rician noise-related bias in PDFF and R 2 * $$ {R}_2^{\ast } $$ estimation, thus addressing a key limitation of existing magnitude-only fitting methods. Our results offer insight into the importance of the noise model for selecting the correct optimum when multiple plausible optima exist.

Thrombus Distribution in Vaccine-induced Immune Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.

Vaccination strategies have been at the forefront of controlling the COVID-19 pandemic. An association between vaccine-induced immune thrombotic thrombocytopenia (VITT) and one of these vaccines, the ChAdOx1 nCov-19 vaccine, is now recognized. The purpose of this study was to investigate the frequency and location of thrombosis in each vascular system using CT, MRI, and US to identify additional sites of thrombus in a United Kingdom-wide sample of patients with confirmed VITT. Thirty-two radiology centers identified through the national collaborative Radiology Academic Network for Trainees were invited from the United Kingdom; seven of these contributed to this study. All patients with confirmed VITT ¬between February 3 and May 12, 2021, who met the inclusion criteria were included. The location and extent of thrombi were evaluated using CT, MRI, and US. A total of 40 patients (median age, 41 years [IQR, 32-52]; 22 [55%] men) with confirmed vaccine-induced immune thrombotic thrombocytopenia after administration of their first ChAdOx1 nCov-19 vaccine were included. Thirty-two patients (80%) developed symptoms within the first 14 days, and eight (20%) developed symptoms within 14-28 days. Twenty-nine patients (72%) experienced neurologic symptoms and were confirmed to have cerebral venous sinus thrombosis, 12 (30%) had clinical deterioration and repeat imaging demonstrated extension of their primary thrombus, and eight (20%) died. Twenty-five of 30 patients (83%) who underwent additional imaging had occult thrombosis. In conclusion, patients with VITT are likely to have multiple sites of thrombosis, with the most frequent being cerebral venous sinus thrombosis in combination with pulmonary embolism and portomesenteric venous thrombosis. Whole-body imaging with contrast-enhanced CT can be used to identify occult thrombosis.

The role of whole-body MRI in musculoskeletal inflammation detection and treatment response evaluation in inflammatory arthritis across age: A systematic review.

OBJECTIVE: To evaluate the relation between whole-body MRI (WBMRI) outcomes and disease activity measures, including clinical examination, composite scores, and other imaging outcomes, and the ability of WBMRI to detect treatment response in patients with inflammatory arthritis (IA) across age. METHODS: Human studies published as full text or abstract in the PubMed and MEDLINE and Cochrane databases from inception to 11th April 2021 were systematically and independently searched by two reviewers. Studies including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), juvenile idiopathic arthritis (JIA) or unclassified inflammatory arthritis (UA) who underwent WBMRI and which reported on disease outcomes were included. RESULTS: Nineteen full-text studies were eligible for inclusion: 2 interventional, 7 retrospective and 10 prospective observational studies, comprising 540 participants (SpA 38.7%, RA 24.8%, JIA 17.8%, PsA 11.5%, healthy controls 5.9%, UA 1.3%). Abstracts of 6 conference papers were reported separately. Five studies in PsA and SpA and 4 in RA measured the frequency of WBMRI-detected and clinically-detected synovitis, and all found the former to be more frequent. Less enthesitis was detected by WBMRI than clinical examination in 5/8 studies. After biologic treatment, the WBMRI inflammation scores declined in 3 studies in SpA and 2 in RA, whilst in 3 studies the results were equivocal. CONCLUSION: The ability of WBMRI to assess disease activity and treatment response in IA was adequate overall. Further studies are needed to corroborate WBMRI findings with IA outcomes and investigate the clinical value of subclinical inflammation.

Do acetabular parameters measured on 2D imaging correlate with CT, and can lateral centre-edge angle predict femoral head coverage?

AIMS: The lateral centre-edge angle (LCEA) is a plain radiological measure of superolateral cover of the femoral head. This study aims to establish the correlation between 2D radiological and 3D CT measurements of acetabular morphology, and to describe the relationship between LCEA and femoral head cover (FHC). METHODS: This retrospective study included 353 periacetabular osteotomies (PAOs) performed between January 2014 and December 2017. Overall, 97 hips in 75 patients had 3D analysis by Clinical Graphics, giving measurements for LCEA, acetabular index (AI), and FHC. Roentgenographical LCEA, AI, posterior wall index (PWI), and anterior wall index (AWI) were measured from supine AP pelvis radiographs. The correlation between CT and roentgenographical measurements was calculated. Sequential multiple linear regression was performed to determine the relationship between roentgenographical measurements and CT FHC. RESULTS: CT-measured LCEA and AI correlated strongly with roentgenographical LCEA (r = 0.92; p < 0.001) and AI (r = 0.83; p < 0.001). Radiological LCEA correlated very strongly with CT FHC (r = 0.92; p < 0.001). The sum of AWI and PWI also correlated strongly with CTFHC (r = 0.73; p < 0.001). CT measurements of LCEA and AI were 3.4° less and 2.3° greater than radiological LCEA and AI measures. There was a linear relation between radiological LCEA and CT FHC. The linear regression model statistically significantly predicted FHC from LCEA, F(1,96) = 545.1 (p < 0.001), adjusted R2 = 85.0%, with the prediction equation: CT FHC(%) = 42.1 + 0.77(XRLCEA). CONCLUSION: CT and roentgenographical measurement of acetabular parameters are comparable. Currently, a radiological LCEA greater than 25° is considered normal. This study demonstrates that those with hip pain and normal radiological acetabular parameters may still have deficiencies in FHC. More sophisticated imaging techniques such as 3D CT should be considered for those with hip pain to identify deficiencies in FHC. Cite this article: Bone Jt Open 2022;3(1):12-19.

Task-driven assessment of experimental designs in diffusion MRI: A computational framework.

This paper proposes a task-driven computational framework for assessing diffusion MRI experimental designs which, rather than relying on parameter-estimation metrics, directly measures quantitative task performance. Traditional computational experimental design (CED) methods may be ill-suited to experimental tasks, such as clinical classification, where outcome does not depend on parameter-estimation accuracy or precision alone. Current assessment metrics evaluate experiments' ability to faithfully recover microstructural parameters rather than their task performance. The method we propose addresses this shortcoming. For a given MRI experimental design (protocol, parameter-estimation method, model, etc.), experiments are simulated start-to-finish and task performance is computed from receiver operating characteristic (ROC) curves and associated summary metrics (e.g. area under the curve (AUC)). Two experiments were performed: first, a validation of the pipeline's task performance predictions against clinical results, comparing in-silico predictions to real-world ROC/AUC; and second, a demonstration of the pipeline's advantages over traditional CED approaches, using two simulated clinical classification tasks. Comparison with clinical datasets validates our method's predictions of (a) the qualitative form of ROC curves, (b) the relative task performance of different experimental designs, and (c) the absolute performance (AUC) of each experimental design. Furthermore, we show that our method outperforms traditional task-agnostic assessment methods, enabling improved, more useful experimental design. Our pipeline produces accurate, quantitative predictions of real-world task performance. Compared to current approaches, such task-driven assessment is more likely to identify experimental designs that perform well in practice. Our method is not limited to diffusion MRI; the pipeline generalises to any task-based quantitative MRI application, and provides the foundation for developing future task-driven end-to end CED frameworks.

Predictors of Hip Dysplasia at 4 Years in Children with Perinatal Risk Factors.

While perinatal risk factors are widely used to help identify those at risk for developmental dysplasia of the hip (DDH) within the first 6 to 8 weeks of life, limited data exist about their association with radiographic evidence of dysplasia in childhood. The purpose of this study was to determine which perinatal risk factors are associated with acetabular dysplasia in children who are ≥2 years of age. METHODS: Pelvic radiographs were made in 1,053 children (mean age, 4.4 years [range, 2 to 7 years]) who had been assessed prospectively as having at least 1 of 9 widely accepted perinatal risk factors for DDH. Two radiologists who were blinded to patient risk factors, history, and age determined the acetabular index (AI). The primary outcome was defined as an AI >2 standard deviations from the Tönnis reference values ("severe" dysplasia). The secondary outcome was an AI of >20° at >2 years of age. The association between risk factors and outcomes was assessed using logistic regression. The effect of treatment in infancy was adjusted for in 37 hips. RESULTS: Twenty-seven participants (3%) showed "severe" hip dysplasia; 3 of these had received treatment for DDH in infancy. Girls were more likely to experience this outcome (odds ratio [OR] = 2.59; 95% confidence interval [CI] = 1.04 to 6.46; p = 0.04); no other examined risk factors were significant. The secondary outcome appeared in 146 participants (14%), 12 of whom had received treatment in infancy. We observed the following predictors for this outcome: female sex (OR = 1.77; 95% CI = 1.21 to 2.59; p = 0.003), breech presentation (OR = 1.74; 95% CI = 1.08 to 2.79; p = 0.02), and being a firstborn child, which had a protective effect (OR = 0.67; 95% CI = 0.46 to 0.96; p = 0.03). CONCLUSIONS: We identified a substantial number of cases that will require at least radiographic surveillance for mild and severe hip dysplasia; 92% had no prior diagnosis of DDH. Those who had been born breech were affected by this outcome even if ultrasonography of the hip had been normal at 6 to 8 weeks, suggesting a benefit from additional radiographic testing. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Assessment of body composition and association with clinical outcomes in patients with lung and colorectal cancer.

Objectives: To assess body composition in patients with non-small cell lung cancer (NSCLC) and colorectal cancer using whole-body MRI and relate this to clinical outcomes. Methods: 53 patients with NSCLC (28 males, 25 females; mean age 66.9) and 74 patients with colorectal cancer (42 males, 32 females; mean age 62.9) underwent staging whole-body MRI scans, which were post-processed to derive fat mass (FM), fat free mass (FFM) and skeletal muscle (SM) indices and SM fat fraction (FF). These were compared between the two cancer cohorts using two-sided t-tests and the chi-squared test. Measurements of body composition were correlated with outcomes including length of hospital stay, metastatic status and mortality. Results: Patients with NSCLC had significantly lower FFM (p = 0.0071) and SM (p = 0.0084) indices. Mean SM FF was greater in patients with NSCLC (p = 0.0124) and was associated with longer hospital stay (p = 0.035). There was no significant relationship between FM, FFM and SM indices and length of hospital stay, metastatic status or mortality. Conclusions: Patients with NSCLC had lower FFM and SM indices than patients with colorectal cancer and greater SMFF, indicating lower SM mass with fatty infiltration. These findings reflect differences in the phenotype of the two groups and suggest patients with lung cancer are more likely to require additional nutritional support. Advances in knowledge: Body composition differs between NSCLC and colorectal cancer. Patients with NSCLC have both a reduced SM mass and greater SM FF suggesting that they are more nutritionally deplete than patients with colorectal cancer.

An information-based comparison of diffusion attenuation models in normal and inflamed bone marrow.

Diffusion-weighted imaging has received attention as a method for characterizing inflammatory exudates in bone marrow in immune-mediated inflammatory diseases and reveals an increase in diffusivity in regions of bone marrow oedema. Various models of diffusion attenuation have been investigated but the model providing the best description of tissue pathophysiology in regions of marrow oedema is unknown. Determining the most appropriate model is an important step towards protocol optimization and the development of a robust and clinically useful method. We aimed to determine which of three candidate models of diffusion attenuation most accurately describes the acquired signal from normal and inflamed bone marrow. 11 subjects with spondyloarthritis and evidence of active inflammation (ie bone marrow oedema) on MRI and 17 patients with no evidence of active inflammation underwent diffusion-weighted imaging of the sacroiliac joints (b-values 0, 50, 100, 300 and 600 s/mm2 ). Monoexponential, intravoxel incoherent motion (IVIM) and kurtosis models were fitted to the acquired signal from regions of interest in areas of bone marrow oedema and normal marrow. The three models were compared in terms of sum of squared error and information content (corrected Akaike information criterion). Model parameters were compared between regions of bone marrow oedema and regions of normal marrow. f the three models investigated, the IVIM model provided the best description of the signal over the 0-600 s/mm2 range across normal and inflamed bone marrow. There was a particular advantage of the IVIM model in normal marrow, where it was best able to capture the pronounced fast diffusion component observed in several cases. However, IVIM and kurtosis effects both became smaller and the signal behaviour became closer to monoexponential in the presence of bone marrow oedema. Our data suggest that increases in Dtissue (in the IVIM framework) might account for the reduced deviation from monoexponential behaviour in oedematous bone.

Histographic analysis of oedema and fat in inflamed bone marrow based on quantitative MRI.

OBJECTIVE: To demonstrate proof-of-concept for a quantitative MRI method using histographic analysis to assess bone marrow oedema and fat metaplasia in the sacroiliac joints. MATERIALS AND METHODS: Fifty-three adolescents aged 12-23 with known or suspected sacroiliitis were prospectively recruited and underwent quantitative MRI (qMRI) scans, consisting of chemical shift-encoded (at 3 T) and diffusion-weighted imaging (at 1.5 T), plus conventional MRI (at 1.5 T) and clinical assessment. qMRI scans produced proton-density fat fraction (PDFF) and apparent diffusion coefficient (ADC) maps of the sacroiliac joints (SIJs), which were analysed using an in-house software tool enabling partially automated ROI definition and histographic analysis. Logistic regression and receiver operating characteristic (ROC) analyses assessed the predictive performance of ADC- and PDFF-based parameters in identifying active inflammation (oedema) and structural damage (fat metaplasia). RESULTS: ADC-based parameters were associated with increased odds of oedema (all p < 0.05); ROC-AUC was higher for histographic parameters representing the upper end of the ADC distribution than for simple averages. Similarly, PDFF-based parameters were associated with increased odds of fat metaplasia (all p < 0.05); ROC area-under-the-curve was higher for histographic parameters representing the upper end of the PDFF distribution than for simple averages. Both ADC- and PDFF-based histographic parameters demonstrated excellent inter- and intra-observer agreement (ICC > 0.9). CONCLUSIONS: ADC-based parameters can differentiate patients with bone marrow oedema from those without, whilst PDFF-based parameters can differentiate patients with fat metaplasia from those without. Histographic analysis might improve performance compared with simple averages such as the mean and median and offers excellent agreement within and between observers. KEY POINTS: • Quantitative MRI with histographic analysis can identify bone marrow oedema (an active inflammatory lesion) and fat metaplasia (a 'chronic' inflammatory lesion) in patients with spondyloarthritis. • The use of histographic analysis might improve the performance of quantitative MRI for detecting bone marrow oedema and fat metaplasia compared with simple averages such as the mean and median. • Bone marrow oedema and fat metaplasia are known to be of diagnostic and prognostic significance, and the proposed method could support clinical decisions around biologic (and other) therapies in spondyloarthritis.

Practical Approaches to Bone Marrow Fat Fraction Quantification Across Magnetic Resonance Imaging Platforms.

BACKGROUND: Quantification of fat by proton density fat fraction (PDFF) measurements may be valuable for the quantification and follow-up of pathology in multicenter clinical trials and routine practice. However, many centers do not have access to specialist methods (such as chemical shift imaging) for PDFF measurement. This is a barrier to more widespread trial implementation. PURPOSE/HYPOTHESIS: To determine the agreement between fat fraction (FF) measurements derived from 1) basic vendor-supplied sequences, 2) basic sequences with offline correction, and 3) specialist vendor-supplied methods. STUDY TYPE: Prospective. POPULATION: Two substudies with ten and five healthy volunteers. FIELD STRENGTH/SEQUENCE: Site A: mDixon Quant (Philips 3T Ingenia); Site B: IDEAL and FLEX (GE 1.5T Optima MR450W); Site C: DIXON, with additional 5-echo gradient echo acquisition for offline correction (Siemens 3T Skyra); Site D: DIXON, with additional VIBE acquisitions for offline correction (Siemens 1.5T Avanto). The specialist method at site A was used as a standard to compare to the basic methods at sites B, C, and D. ASSESSMENT: Regions of interest were placed on areas of subchondral bone on FF maps from the various methods in each volunteer. STATISTICAL TESTS: Relationships between FF measurements from the various sites and Dixon methods were assessed using Bland-Altman analysis and linear regression. RESULTS: Basic methods consisting of IDEAL, LAVA FLEX, and DIXON produced FF values that were linearly related to reference FF values (P < 0.0001), but produced mean biases of up to 10%. Offline correction produced a significant reduction in bias in both substudies (P < 0.001). DATA CONCLUSION: FF measurements derived using basic vendor-supplied methods are strongly linearly related with those derived using specialist methods but produce a bias of up to 10%. A simple offline correction that is accessible even when the scanner has only basic sequence options can significantly reduce bias. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;52:298-306.

Whole body MRI in multiple myeloma: Optimising image acquisition and read times.

OBJECTIVE: To identify the whole-body MRI (WB-MRI) image type(s) with the highest value for assessment of multiple myeloma, in order to optimise acquisition protocols and read times. METHODS: Thirty patients with clinically-suspected MM underwent WB-MRI at 3 Tesla. Unenhanced Dixon images [fat-only (FO) and water-only (WO)], post contrast Dixon [fat-only plus contrast (FOC) and water-only plus contrast (WOC)] and diffusion weighted images (DWI) of the pelvis from all 30 patients were randomised and read by three experienced readers. For each image type, each reader identified and labelled all visible myeloma lesions. Each identified lesion was compared with a composite reference standard achieved by review of a complete imaging dataset by a further experienced consultant radiologist to determine truly positive lesions. Lesion count, true positives, sensitivity, and positive predictive value were determined. Time to read each scan set was recorded. Confidence for a diagnosis of myeloma was scored using a Likert scale. Conspicuity of focal lesions was assessed in terms of percent contrast and contrast to noise ratio (CNR). RESULTS: Lesion count, true positives, sensitivity and confidence scores were significantly higher when compared to other image types for DWI (P<0.0001 to 0.003), followed by WOC (significant for sensitivity (P<0.0001 to 0.004), true positives (P = 0.003 to 0.049) and positive predictive value (P< 0.0001 to 0.006)). There was no statistically significant difference in these metrics between FO and FOC. Percent contrast was highest for WOC (P = 0.001 to 0.005) and contrast to noise ratio (CNR) was highest for DWI (P = 0.03 to 0.05). Reading times were fastest for DWI across all observers (P< 0.0001 to 0.014). DISCUSSION: Observers detected more myeloma lesions on DWI images and WOC images when compared to other image types. We suggest that these image types should be read preferentially by radiologists to improve diagnostic accuracy and reporting efficiency.

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis.

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA. Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA. Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA. Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications. Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.