New trends in MRI of cartilage: Advances and limitations in small animal studies

Goebel, Jean-Christophe; Pinzano, Astrid; Grenier, Denis; Perrier, Anne-Laure; Henrionnet, Christel; Galois, Laurent; Gillet, Pierre; Beuf, Olivier

doi:10.3233/bme-2010-0631

Cited by 15 publications

(16 citation statements)

References 21 publications

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“…In addition, allowing a shorter duration between imaging sessions (that is, two weeks) may improve our detection of edema in the early stages of OA progression and SBC formation. With the advancement of custom designed rat knee coils [39] that incorporate longer scan times for increased signal-to-noise ratio, it will be feasible to further quantify the tissue composition of SBC over time, without reliance on tissue-destructive, end-stage histological analysis. This is further evident in the recent work using the rat model of secondary OA, combined with dual-modality imaging that demonstrated the utility of longitudinal imaging when evaluating the effect of anti-inflammatory drugs on disease progression [23].…”

Section: Discussionmentioning

confidence: 99%

An in vivoinvestigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

et al. 2012

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IntroductionSubchondral bone cysts (SBC) have been identified in patients with knee osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA.MethodsEight rodents underwent anterior cruciate ligament transection and partial medial meniscectomy (ACLX) of the right knee. In vivo 9.4 T MRI and micro-computed tomography (micro-CT) scans were performed consecutively prior to ACLX and 4, 8, and 12 weeks post-ACLX. Resultant images were co-registered using anatomical landmarks, which allowed for precise tracking of SBC size and composition throughout the study. The diameter of the SBC was measured, and the volumetric bone mineral density (vBMD) was calculated within the bone adjacent to SBC. At 12 weeks, the ACLX and contralateral knees were processed for histological analysis, immunohistochemistry, and Osteoarthritis Research Society International (OARSI) pathological scoring.ResultsAt 4 weeks post-ACLX, 75% of the rodent knees had at least 1 cyst that formed in the medial tibial plateau; by 12 weeks all ACLX knees contained SBC. Imaging data revealed that the SBC originate in the presence of a subchondral bone plate breach, with evolving composition over time. The diameter of the SBC increased significantly over time (P = 0.0033) and the vBMD significantly decreased at 8 weeks post-ACLX (P = 0.033). Histological analysis demonstrated positive staining for bone resorption and formation surrounding the SBC, which were consistently located beneath the joint surface with the greatest cartilage damage. Trabecular bone adjacent the SBC lacked viable osteocytes and, combined with bone marrow changes, indicated osteonecrosis.ConclusionsThis study provides insight into the mechanisms leading to SBC formation in knee OA. The expansion of these lesions is due to stress-induced bone resorption from the incurred mechanical instability. Therefore, we suggest these lesions can be more accurately described as a form of OA-induced osteonecrosis, rather than 'subchondral cysts'.

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Section: Discussionmentioning

confidence: 99%

An in vivoinvestigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

et al. 2012

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“…Although differences in mineralization and hypertrophy were not commented on in this study, it can be inferred that the mineralization and inferior cartilage tissue formation seen in many in vivo subcutaneous implantation studies may arise from the unnatural implantation environment, and so results may be more promising within a true cartilage defect model. Additionally, further development of new or existing imaging systems, such as EPIC-μCT [107,108] and MRI imaging [109], that could be used in in vivo studies without need for sacrifice would be beneficial, allowing the progress of the same samples to be tracked over time and requiring fewer animals. Better standards for cartilage-focused studies will improve understanding of the effects of material design on cartilage tissue formation and may in turn help to further develop previously studied materials.…”

Section: Future Directions and Additional Considerationsmentioning

confidence: 99%

Hydrogel design for cartilage tissue engineering: A case study with hyaluronic acid

2011

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Hyaline cartilage serves as a low-friction and wear-resistant articulating surface in load-bearing, diarthrodial joints. Unfortunately, as the avascular, alymphatic nature of cartilage significantly impedes the body’s natural ability to regenerate, damage resulting from trauma and osteoarthritis necessitates repair attempts. Current clinical methods are generally limited in their ability to regenerate functional cartilage, and so research in recent years has focused on tissue engineering solutions in which the regeneration of cartilage is pursued through combinations of cells (e.g., chondrocytes or stem cells) paired with scaffolds (e.g., hydrogels, sponges, and meshes) in conjunction with stimulatory growth factors and bioreactors. A variety of synthetic and natural materials have been employed, most commonly in the form of hydrogels, and these systems have been tuned for optimal nutrient diffusion, connectivity of deposited matrix, degradation, soluble factor delivery, and mechanical loading for enhanced matrix production and organization. Even with these promising advances, the complex mechanical properties and biochemical composition of native cartilage have not been achieved, and engineering cartilage tissue still remains a significant challenge. Using hyaluronic acid hydrogels as an example, this review will follow the progress of material design specific to cartilage tissue engineering and propose possible future directions for the field.

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“…Furthermore, many of the molecular pathways activated in cartilage in PTOA are shared by mice and humans Standard imaging such as radiographic joint space narrowing or 3T‐MRI lack sensitivity to detect cartilage damage in mice, impeding clinical translation . Recent technological advances and development of novel imaging modalities may bridge this gap …”

Section: What Is Post‐traumatic Osteoarthritis (Ptoa)?mentioning

confidence: 99%

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Blaker

Clarke

Little

2016

Journal Orthopaedic Research

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Post-traumatic osteoarthritis (PTOA) is defined by its development after joint injury. Factors contributing to the risk of PTOA occurring, the rate of progression, and degree of associated disability in any individual, remain incompletely understood. What constitutes an "OA-inducing injury" is not defined. In line with advances in the traumatic brain injury field, we propose the scope of PTOA-inducing injuries be expanded to include not only those causing immediate structural damage and instability (Type I), but also those without initial instability/damage from moderate (Type II) or minor (Type III) loading severity. A review of the literature revealed this full spectrum of potential PTOA subtypes can be modeled in mice, with 27 Type I, 6 Type II, and 4 Type III models identified. Despite limitations due to cartilage anatomy, joint size, and bio-fluid availability, mice offer advantages as preclinical models to study PTOA, particularly genetically modified strains. Histopathology was the most common disease outcome, cartilage more frequently studied than bone or synovium, and meniscus and ligaments rarely evaluated. Other methods used to examine PTOA included gene expression, protein analysis, and imaging. Despite the major issues reported by patients being pain and biomechanical dysfunction, these were the least commonly measured outcomes in mouse models. Informative correlations of simultaneously measured disease outcomes in individual animals, was rarely done in any mouse PTOA model. This review has identified knowledge gaps that need to be addressed to increase understanding and improve prevention and management of PTOA. Preclinical mouse models play a critical role in these endeavors. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:424-439, 2017.

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New trends in MRI of cartilage: Advances and limitations in small animal studies

Cited by 15 publications

References 21 publications

An in vivoinvestigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

An in vivoinvestigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

Hydrogel design for cartilage tissue engineering: A case study with hyaluronic acid

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

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