Emerging quantitative MR imaging biomarkers in inflammatory arthritides

PURPOSE: To review quantitative magnetic resonance imaging (qMRI) methods for imaging inflammation in connective tissues and the skeleton in inflammatory arthritis. This review is designed for a broad audience including radiologists, imaging technologists, rheumatologists and other healthcare professionals. METHODS: We discuss the use of qMRI for imaging skeletal inflammation from both technical and clinical perspectives. We consider how qMRI can be targeted to specific aspects of the pathological process in synovium, cartilage, bone, tendons and entheses. Evidence for the various techniques from studies of both adults and children with inflammatory arthritis is reviewed and critically appraised. RESULTS: qMRI has the potential to objectively identify, characterize and quantify inflammation of the connective tissues and skeleton in both adult and pediatric patients. Measurements of tissue properties derived using qMRI methods can serve as imaging biomarkers, which are potentially more reproducible and informative than conventional MRI methods. Several qMRI methods are nearing transition into clinical practice and may inform diagnosis and treatment decisions, with the potential to improve patient outcomes. CONCLUSIONS: qMRI enables specific assessment of inflammation in synovium, cartilage, bone, tendons and entheses, and can facilitate a more consistent, personalized approach to diagnosis, characterisation and monitoring of disease

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

Simultaneous Quantification of Bone Edema/Adiposity and Structure in Inflamed Bone Using Chemical Shift-Encoded MRI in Spondyloarthritis

PURPOSE: To evaluate proton density fat fraction (PDFF) and R2* as markers of bone marrow composition and structure in inflamed bone in patients with spondyloarthritis. METHODS: Phantoms containing fat, water, and trabecular bone were constructed with proton density fat fraction (PDFF) and bone mineral density (BMD) values matching those expected in healthy bone marrow and disease states, and scanned using chemical shift-encoded MRI (CSE-MRI) at 3T. Measured PDFF and R2* values in phantoms were compared with reference FF and BMD values. Eight spondyloarthritis patients and 10 controls underwent CSE-MRI of the sacroiliac joints. PDFF and R2* in areas of inflamed bone and fat metaplasia in patients were compared with normal bone marrow in controls. RESULTS: In phantoms, PDFF measurements were accurate over the full range of PDFF and BMD values. R2* measurements were positively associated with BMD but also were influenced by variations in PDFF. In patients, PDFF was reduced in areas of inflammation and increased in fat metaplasia compared to normal marrow. R2* measurements were significantly reduced in areas of fat metaplasia. CONCLUSION: PDFF measurements reflect changes in marrow composition in areas of active inflammation and structural damage and could be used for disease monitoring in spondyloarthritis. R2* measurements may provide additional information bone mineral density but also are influenced by fat content

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

Quantifying bone structure, micro-architecture, and pathophysiology with MRI

The radiology of bone has been transformed by magnetic resonance imaging, which has the ability to interrogate bone's complex architecture and physiology. New techniques provide information about both the macrostructure and microstructure of bone ranging from micrometre detail to the whole skeleton. Furthermore functional information about bone physiology can be used to detect disease early before structural changes occur. The future of bone imaging is in quantifying the anatomical and functional information to diagnose and monitor disease more precisely. This review explores the state of the art in quantitative MRI bone imaging

Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology

Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (for example, in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. Magnetic resonance imaging (MRI) is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has therefore emerged as an objective, image-based biomarker of disease. Methods for fat fraction quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method - and correct interpretation - can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians

Sacroiliac Joint Ankylosis In Young Spondyloarthritis Patients Receiving Biologic Therapy: Observation of Serial MRI scans

Objectives: To assess the temporal relationship between initiating biologic therapy and magnetic resonance imaging (MRI) scores of inflammation and structural damage in young patients with spondyloarthritis. / Methods: A local adolescent rheumatology database was searched for patients aged 12 – 24 years with sacroiliitis on MRI and a clinical diagnosis of enthesitis‐related arthritis (ERA) or non‐radiographic axial spondyloarthritis. Patients treated with tumour necrosis factor inhibitor (TNFi) therapy with a minimum of one scan before and two after starting TNFi therapy (over ≥ 2 years) were included. Images of the sacroiliac joints were scored for inflammation and structural abnormalities (including erosions, fat metaplasia and fusion). The effects of TNFi therapy and of time since initiation of TNFi therapy on inflammation and structural abnormalities were assessed using a mixed‐effects regression analysis. / Results: Twenty‐nine patients aged 12‐23 years undergoing TNFi therapy were included. Inflammation scores were significantly lower in patients on treatment (P=0.013), but there was no significant effect of time from TNFi initiation on inflammation (P=0.125). Conversely, there was no significant effect of treatment itself on fusion scores (P=0.285), but fusion scores significantly increased with time from TNFi initiation (P=0.000). A similar pattern was observed for fat metaplasia. Fusion scores did not change in the first year after starting TNFi therapy (P=0.108), but were significantly increased at all subsequent time points (P=0.000 to 0.001). / Conclusions: TNFi therapy failed to prevent the eventual development of joint ankylosis in this cohort, despite a substantial reduction in inflammation with TNFi therapy

Diffusion-weighted imaging is a sensitive biomarker of response to biologic therapy in enthesitis-related arthritis

OBJECTIVE: The aim was to evaluate diffusion-weighted imaging (DWI) as a tool for measuring treatment response in adolescents with enthesitis-related arthropathy (ERA). METHODS: Twenty-two adolescents with ERA underwent routine MRI and DWI before and after TNF inhibitor therapy. Each patient’s images were visually scored by two radiologists using the Spondyloarthritis Research Consortium of Canada system, and sacroiliac joint apparent diffusion coefficient (ADC) and normalized ADC (nADC) were measured for each patient. Therapeutic clinical response was defined as an improvement of 5 30% physician global assessment and radiological response defined as 52.5-point reduction in Spondyloarthritis Research Consortium of Canada score. We compared ADC and nADC changes in responders and non-responders using the MannWhitneyWilcoxon test. RESULTS: For both radiological and clinical definitions of response, reductions in ADC and nADC after treatment were greater in responders than in non-responders (for radiological response: ADC: P < 0.01; nADC: P = 0.055; for clinical response: ADC: P = 0.33; nADC: P = 0.089). ADC and nADC could predict radiological response with a high level of sensitivity and specificity and were moderately sensitive and specific predictors of clinical response (the area under the receiver operating characteristic curves were as follows: ADC: 0.97, nADC: 0.82 for radiological response; and ADC: 0.67, nADC: 0.78 for clinical response). CONCLUSION: DWI measurements reflect the response to TNF inhibitor treatment in ERA patients with sacroiliitis as defined using radiological criteria and may also reflect clinical response. DWI is more objective than visual scoring and has the potential to be automated. ADC/nADC could be used as biomarkers of sacroiliitis in the clinic and in clinical trials