A SAMPLE RAPID MRI ACQUISITION PROTOCOL SUPPORTING ASSESSMENT OF MULTIPLE ARTICULAR TISSUES AND PATHOLOGIES IN EARLY AND ADVANCED KNEE OSTEOARTHRITIS

INTRODUCTION Assessing the structure and properties of articular tissues using MRI-based approaches is highly relevant to OA studies, as MRI enables direct visualization of all joint structures. These can be evaluated using semi-quantitative (sq) or quantitative (q) morphometric methods. Insights into the biochemical composition of specific tissues can be obtained with MRI T2 relaxometry. A crucial basis for such OA analysis is the choice of a suitable, and time-efficient MRI acquisition protocol that assures high image quality while lowering patient burden and costs through short scan time. Moreover, standardization of MRI protocols and analysis techniques across studies is helpful to ensure comparability between studies. OBJECTIVE To propose - as an expert opinion - a state-of-the-art MRI acquisition protocol for clinical trials on both early and advanced stages of knee OA. This protocol is designed to support a multitude of semi-quantitative and quantitative image assessments (including synovitis), relevant to the study and management of knee OA, and ideally suitable for automated analysis. METHODS A PubMed literature search of articles published in the last 20 years was performed (focus on the past 5 years) and several OA imaging experts provided input. Specific MRI sequences (including orientations, spatial resolutions, and parameters) were identified that support the above purpose. The implementation of the protocol had to be feasible on standard clinical MRI scanners, with a net acquisition time of <30 minutes. RESULTS The proposed protocol is shown in Tables 1 & 2, and example images in Figure 1. MRIs should be obtained at ≥1.5T, ideally without hardware (or major software) changes during longitudinal studies. Localizer images should be used to spatially align the sequences with the knee anatomy and position. We recommend clinical 2D proton density (PD) turbo spin echo sequences (TSE) with fat suppression (FS) in two planes, and a coronal T1-weighted TSE (without FS) to support sq assessment of all articular tissues and pathologies, and q assessment of Hoffa and effusion synovitis. A high-resolution 3D quantitative double echo steady state (qDESS) sequence [1] is proposed (coronal, or sagittal, or sagittal near-isotropic) for quantitative cartilage morphometry and T2, for bone (shape) and for q meniscus analysis. Inversion recovery spin echo (FLAIR [2]) is included for potential non-contrast-enhanced depiction of synovitis. All images should be checked for quality and protocol adherence as soon as possible (best immediately) after image acquisition. Acquiring repeated scans (re-test) in a few patients per site at baseline and follow-up can provide information on study-specific test-retest errors and the smallest detectable change (SDC). CONCLUSION Here, we propose a state-of-the-art image acquisition protocol for trials on early or advanced knee OA. While assuring technical feasibility in clinical research, a balance between image acquisition efficiency (time), safety, and technical/methodological diversity is proposed. Importantly, the suggested approach offers potential for scientific innovation in the (automated) analysis of tissue structures, composition and pathology in clinical trials on disease modification of knee OA.