Meniscus pathology may promote early osteoarthritis. this study assessed human meniscus functionality (i.e. its response to loading) ex vivo based on quantitative T1, T1ρ, and T2 mapping as a function of histological degeneration and loading. Forty-five meniscus samples of variable degeneration were harvested from the lateral meniscus body region of 45 patients during total knee arthroplasties. Samples underwent serial mapping on a 3.0-T MRI scanner (Achieva, Philips) using a force-controlled and torque-inducing compressive loading device. Samples were measured at three loading positions, i.e. unloaded, loaded to 2 bar (compression force 37 N) and 4 bar (69 N). Histology (Pauli classification) and biomechanics (Elastic Modulus) served as references. Based on histology, samples were trichotomized as grossly intact (n = 14), mildly degenerative (n = 16), and moderate-to-severely degenerative (n = 15) and analyzed using appropriate parametric and non-parametric tests. For T1, we found loading-induced decreases in all samples, irrespective of degeneration. For T1ρ, zonal increases in intact (apex) and decreases in degenerative samples (base) were found, while for T2, changes were ambiguous. In conclusion, force-controlled loading and serial MR imaging reveal response-to-loading patterns in meniscus. Zonal T1ρ response-to-loading patterns are most promising in differentiating degeneration, while T1 and T2 aren't clearly related to degeneration.and may provide an imaging-based indication of functional tissue properties. Acute and chronic meniscus pathologies are frequent clinical entities 1. Due to its decisive role in load bearing, load transmission, load dissipation and in providing joint stability, congruity and lubrication 2 , meniscus integrity in form and function is of utmost importance to the knee joint's long-term health 3. Meniscus functionality, which is the tissue's ability to function properly, i.e. to disperse loads and reduce friction, is heavily dependent on its extracellular matrix properties. Collagen fibers, primarily type-I, define the tissue's tensile strength and shock-absorbing properties, while proteoglycans contribute to compressive strength by upholding swelling pressure 2,4,5. Lately, therapeutic efforts have been aimed at preserving and restoring the damaged meniscus secondary to trauma or degeneration 6,7. This is of particular relevance as meniscus and cartilage pathologies are closely interrelated. Consequently, meniscus damage and loss are key features of and risk factors for developing osteoarthritis (OA) 8. The discussion on whether meniscus pathologies are a cause or consequence of knee OA is ongoing 9,10. Yet common consensus prevails that morphological meniscus defects, i.e. surface breakdown and tissue tearing, are the consequence of degenerative changes of the extracellular matrix 11-13 , and contribute to the evolution of OA by altering load distribution and transmission to the adjacent articular cartilage. Hence, detecting such degenerative changes early is necessary in therapeu...

Background:In OA, there is a close association of meniscus and cartilage pathologies. Meniscus degeneration and lesioning are critical risk factors for development of early OA. Hence, thisex-vivostudy assessed the responses to standardized loading of human meniscus samples as a function of degeneration and based on changes in their T1, T2 and T1ρ maps (as surrogate parameters of the tissue’s functionality).Objectives:Can meniscus functionality be visualized by serial quantitative MRI mapping technics?Methods:During total knee replacements, 45 meniscus samples of variable degeneration were harvested from the center of the lateral meniscus body (Fig. 1a1-a3). After preparation to standard, samples were subject to force-controlled loading using an MRI-compatible lever device that created compressive loading by torque ((Fig. 1a4-a5). For each sample and loading position, MRI measurements (as detailed below) were performed in the unloaded (δ0) and loaded configurations, i.e. loaded to 2 bar (δ1, 37.1 N compressive force, 0.67 Nm torque) and to 4 bar (δ2, 69.1 N, 1.24 Nm). Throughout all loading positions, morphological and quantitative imaging was performed using Proton Density-weighted and T1, T1ρ, and T2 mapping sequences (3.0 T, Achieva, Philips) based on standard turbospin-echo, inversion-recovery, spin-lock multi-gradient-echo, and multi-spin-echo sequences. For reference purposes, histological (i.e. Pauli classification) and biomechanical measures (i.e. Elastic Modulus) were obtained for each sample. Based on Pauli sum scores, samples were trichotomized as grossly intact, (n=14), mildly degenerated (n=16), and moderate-to-severely degenerated (n=15).Figure 1.Preparation of meniscus samples and details of the MRI-compatible loading device. The lateral meniscus (a1) was cut to standard size by use of a dedicated cutting block (a2) to eventually obtain lateral meniscus samples (from the body region) of standard dimensions (a3). These samples were then placed in a dedicated MRI-compatible loading device for pressure-controlled, quasi-static and torque-induced loading under simultaneous MR imaging (a4). Two parallel support beams allowed standardized positioning in the MRI scanner‘s bore (a5).Results:Morphologically, loading induced deformation and flattening in all samples (Fig. 2a). For T1, homogeneous loading-induced decreases in all samples were found, irrespective of degeneration (Fig. 2b). For T1ρ, increases in the apical zones of intact samples were observed, and decreases in degenerated samples (Fig. 2c). For T2, changes were ambiguous and incoherent (Fig. 2d).Figure 2.Serial morphological images and functional maps of histologically moderately degenerative human meniscus as a function of force-controlled loading. Serial PDw (a), T1 (b), T1ρ (c), and T2 maps (d) are displayed at increasing loading intensity (δ0: unloaded [a1-d1]; δ1: loaded to 2 bar [a2-d2]; δ2: loaded to 4 bar [a3-d3]). Histologically, this sample demonstrated signs of severe surface desintegration and disruption. Pauli sum score 12, i.e. moderate to severe degeneration (Pauli Grade III). In b – d, color-coded parameter value maps are overlaid onto the corresponding morphological images. Histological sections are stained with Hematoxylin-Eosin (e1) and Safranin O (e2).Conclusion:Meniscus functionality may be visualized using serial quantitative MRI mapping techniques. T1ρ may provide an imaging biomarker of relevant intra-tissue adaptations that seem to be associated with histological degeneration. The perspective evaluation of meniscus functionality may be indicative of incipient or manifest load transmission failure to the adjacent cartilage layer.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Lisa Dötsch: None declared, Daniel Truhm: None declared, Daniel Abrar: None declared, Sven Nebelung: None declared

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