Recipient Organization
UNIV OF MINNESOTA
(N/A)
ST PAUL,MN 55108
Performing Department
Veterinary Population Medicine
Non Technical Summary
Osteochondrosis (OC) and its clinically apparent form, osteochondrosis dissecans (OCD), are some of the most common developmental orthopaedic diseases affecting horses and have enormous impact on the equine industry. Osteochondrosis is a highly dynamic disease, with lesions developing and healing over the first year of life. Although early OC lesions may heal with conservative treatment, lesions that persist beyond joint-specific time points or that include clefts that extend through the articular cartilage are unlikely to resolve without surgical intervention.The primary objective of the proposed study is to use MRI to identify lesions of subclinical OC in foals predisposed to OCD and/or suspected to have OC based on radiographic screening. We hypothesize that quantitative MRI techniques (T2 cartilage maps) are able to identify early subclinical lesions of OC and can be used to monitor lesion healing or progression. We also hypothesize that MRI will allow identification of markers predictive of the healing potential of individual OC lesions.During the first stage of the study, stifle and hock joint specimens harvested from foals predisposed to OCD or suspected of suffering from subclinical OC will be evaluated. At predilection sites of OC, T2 cartilage maps will be obtained using a clinically available 3T MR scanner with the aim of identifying areas of epiphyseal cartilage necrosis characterized by increased T2 relaxation times. MRI findings will be validated by histological examination of the imaged sites. During the second stage of the study, MRI techniques evaluated during the cadaveric specimen studies will be tested forapplication in live foals. Young foals predisposed to OC and/or diagnosed with subclinical OC will undergoMRI to obtain T2 cartilage maps of their hock and stifle joints. Cartilage maps will be evaluated for changes consistent with the presence of epiphyseal cartilage necrosis. Progression or resolution of subclinical OC lesions will be monitored using consecutive MRI exams at 2 month intervals until 12 month of age, when lesions are considered permanent or until complete healing of the lesion, whichever occurs first. Lesion characteristics (size, location, T2 relaxation times) will be evaluated for their ability to predict lesion healing or progression. Twelve-month-old foals with MRI diagnosis of OCD will undergo arthroscopic surgery to confirm the diagnosis of OCD.
Animal Health Component
50%
Research Effort Categories
Basic
(N/A)
Applied
50%
Developmental
50%
Goals / Objectives
Specific Aim 1: Evaluate novel MRI sequences with immediate clinical availability for their ability to identify early lesions of OC.Hypothesis: T2 maps obtained at clinically relevant field strength (1.5 or 3 Tesla) are able to identify areas of epiphyseal cartilage necrosis, the hallmark of subclinical OC, in ex vivo equine joint specimens.Specific Aim 2: Identify and monitor progression vs. healing of subclinical OC lesions in young foals using bimonthly MRI exams with the aim of identifying specific markers of healing vs. progression.Hypothesis: T2 maps obtained in vivo are able to identify lesions of subclinical OC in foals; alterations in T2 relaxation time of OC lesions along with the size and location of the subclinical lesion can be used as predictors of lesion healing vs. progression
Project Methods
Specific aim 1: Evaluate novel MRI sequences with immediate clinical availability for their ability to identify early lesions of osteochondrosis (OC).In this aim, T2 cartilage maps will be generated in a clinically available MR scanner with the aim of identifying areas of ischemic cartilage necrosis, OC latens, ex vivo using equine stifle and hock joint explants.Stifle and hock joints will be harvested from cadavers of foals (n=5) aged 3 - 6 months predisposed to OC based on familial history of the disease. Specimens will be collected from foal cadavers presented to the University of Minnesota Veterinary Diagnostic Laboratory for diagnostic necropsy, as well as from foals euthanized on the field by veterinarians. Distal femora, tibiae and tali will be freed from their soft tissue attachments and will be stored wrapped in saline soaked sponges at -20 C prior to MRI studies.Collected specimens will undergo MRI at the College of Veterinary Medicine using the 3T GE MR scanner available on site. T2 cartilage maps will be obtained from known predilection sites of OC in each joint, including the proximal and middle third of the lateral and medial trochlear ridges of the femur, the distal intermediate ridge and medial malleolus of the distal tibia, and the distal aspects of the lateral and medial trochlear ridges of the talus. MRI findings will be evaluated for the presence of discrete areas of increased relaxation time in the T2 maps confined to the epiphyseal cartilage, which is consistent with epiphyseal cartilage necrosis (OC latens).At the conclusion of the MRI evaluations, specimens will be fixed in formalin for 48h then decalcified using EDTA solution. Decalcified specimens will be serially sectioned into 3 mm thick blocks matching the planes of the MRI and processed for routine histology. Five μm thick sections cut from the surface of the blocks, matching the location of the MRI slices, will be stained with hematoxylin and eosin and Safranin O. To validate the MRI findings, histological sections will be evaluated for the presence of necrotic epiphyseal cartilage, characterized by decreased Safranin O staining of the extracellular matrix and karyopyknosis on the H&E sections, in areas corresponding with regions of increased T2 relaxation time in the matching MRI slicesSpecific Aim 2: Identify and monitor progression vs. healing of subclinical OC lesions in young foals using bimonthly MRI exams with the aim of identifying specific markers of healing vs. progression.In these in vivo experiments foals predisposed to OC will undergo MRI of their hock and stifle joint using T2 maps to demonstrate the presence of epiphyseal cartilage necrosis and monitor its progression vs. healing.Foals (n=5) aged 4 to 6 months old with unilateral OC of the stifle and/or hock joints or with breeding history (OCD in dam and/or sire) consistent with high likelihood of OC will be enrolled in the study. Diagnosis of unilateral OC will be established based on the presence of unexplained joint effusion and associated mild lameness without marked radiographic changes in the affected joint (Dabareiner et al., 1993). At the time of enrollment foals will undergo in vivo MRI evaluation to obtain T2 cartilage maps both the affected and the contralateral stifle and hock joints. Foals confirmed with subclinical OC during the first MRI session will undergo repeated MRI at 2 month intervals until 1 year of age, at which time OC(D) lesions are expected to be either permanent or healed (Dik et al., 1999). Foals with persisting lesions of OCD will undergo treatment using arthroscopy, which will also serve to confirm the diagnosis.At the conclusion of the study, lesions identified using the T2 maps will be divided into two categories (healed OC lesion vs. clinical OCD) and the MRI findings will be evaluated retrospectively to identify markers predictive of lesion healing or progression. Parameters evaluated will include the T2 relaxation time of the lesion at the time of presentation, temporal changes in its T2 relaxation time (increasing vs. decreasing over time), as well as location and size of the OC lesion.