Diagnostic Value of a Biomarker of Non-surgical Knee Osteoarthritis

Lille Catholic University130 enrolled

Overview

Osteoarthritis is a very common pathology, especially in an aging population, and a source of disability. Based on standard radiography, the diagnosis is performed late based on the loss of the cartilage thickness. In this context, prosthetic replacement of the joint is a frequent outcome. New diagnostic biomarkers and herapeutic targets are therefore logically research priorities identified by the European League Against Rheumatisms, osteoarthritis ad hoc committee. The inflammation related to the development of this pathology is mainly studied at the cellular level and essentially in animals. Since inflammatory and vascular phenomena are closely intertwined, medical imaging of the subchondral bone vascularization appears interesting. The dynamic contrast-enhanced T1 Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique allows the identification of changes in the osteoarthritic subchondral bone vascularization. In osteoarthritic animals, these changes could be identified before the cartilaginous lesions became visible, and could be correlated with the severity of osteoarthritis. This study would be the first to correlate subchondral bone perfusion measurements (performed with the DCE sequence) of early cartilaginous lesions of the knee, identified by non-invasive MRI (T2 mapping) in humans. This examination will be performed on a 3 Tesla MRI. If a correlation is demonstrated in the early stages of osteoarthritis in both humans and animals, then infusion of subchondral bone could become a biomarker of osteoarthritis, and serve as a follow-up evaluation of future treatments.

Osteoarthritis is a very common pathology, especially in an aging population, and a source of disability. Based on standard radiography, the diagnosis is performed late because it is based on the loss of cartilage thickness. In this context, prosthetic replacement of the joint is a frequent outcome. New diagnostic biomarkers and new therapeutic targets are therefore logically research priorities identified up today by the European League Against Rheumatisms, osteoarthritis ad hoc committee . The strictly mechanical nature of osteoarthritis is currently being questioned. Indeed, the primitive role of inflammation in the development of this pathology is more and more discussed. This inflammation is today studied at the cellular level and essentially in animals. Since inflammatory and vascular phenomena are closely intertwined, medical imaging of the subchondral bone vascularization appears interesting. The dynamic contrast-enhanced T1 Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique allows the identification of changes in the osteoarthritic subchondral bone vascularization. In osteoarthritic animals, these changes could be identified before the cartilaginous lesions became visible, and could be correlated with the severity of osteoarthritis. In humans, a preliminary investigator study has recently shown that these changes correlate with the importance of osteoarthritic lesions in patients with advanced osteoarthritis. Up to date, no clinical study has so far been initiated to evaluate the diagnostic value of vascularization markers of subchondral bone in early knee osteoarthritis. In this context, this prospective monocentric study aims to define the role of DCE medical imaging in the diagnosis of early (non-surgical) patella-femoral osteoarthritis. This study would be the first to correlate subchondral bone perfusion measurements (performed with the DCE sequence) with early cartilaginous lesions, identified by non-invasive MRI (T2 mapping) in humans. This examination will be performed on a 3 Tesla MRI. If a correlation is demonstrated in the early stages of osteoarthritis in both humans and animals, then infusion of subchondral bone could become a biomarker of osteoarthritis, and serve as a follow-up evaluation of future treatments.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 59 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Patients ≥ 18 years old and \< 60 years old * Asymptomatic at the patella-femoral joint * Coming to perform a medical imaging examination for another indication, in the medical imaging department of the GHICL * Patient being informed and given free, informed and written consent to participate * Affiliated to the social security Exclusion Criteria: * Medical history of traumatic ligamentous, meniscal or cartilaginous lesion * Medical history of knee surgery * Contraindications to MRI (pacemaker, ferromagnetic vascular clip, infusion pump, neurostimulator, cochlear implant, suspicion of metallic foreign body, claustrophobia, ...) * MRI with gadoteric acid injection in the 7 days preceding the MRI of the knee * Hypersensitivity to gadoteric acid, meglumine or any drug containing gadolinium, or any other contrast medium * Medical history of severe allergy, uncontrolled asthma, treatment with beta-blocker * Renal insufficiency: glomerular filtration less than 30 mL/min * Pregnant or nursing woman * Patient under tutorship or curatorship

Outcomes

Primary Outcomes

Correlation between T2 cartilage value and endothelial transfer constant (Ktrans)

T2 (transverse relaxation time) mapping can evaluate the status of the cartilage matrix and identify biochemical changes. T2 is the time constant which determines the rate at which excited protons reach equilibrium or go out of phase with each other. It is a measure of the time taken for spinning protons to lose phase coherence among the nuclei spinning perpendicular to the main field. Ktrans is a constant representing the volume transfer between blood plasma and extravascular extracellular space. its units are given in values of (1/time)