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Advances in current clinical modalities, including magnetic resonance imaging and computed tomography, allow for earlier diagnoses of cartilage damage that could mitigate progression to osteoarthritis. However, current imaging modalities do not detect submicrometer damage. Developments in in vivoor arthroscopic techniques, including optical coherence tomography, ultrasonography, bioelectricity including streaming potential measurement, noninvasive electroarthrography, and multiphoton microscopy can detect damage at an earlier time point, but they are limited by a lack of penetration and the ability to assess an entire joint. This article reviews current advancements in clinical and developing modalities that can aid in the early diagnosis of cartilage injury and facilitate studies of interventional therapeutics.

Objective: The aim of this study was to determine if the noninvasive or minimally invasive and nondestructive imaging techniques of quantitative T2-mapping or multiphoton microscopy (MPM) respectively, could detect differences in cartilage collagen orientation similar to polarized light microscopy (PLM). It was hypothesized that MRI, MPM, and PLM would all detect quantitative differences between repair and normal cartilage tissue.Methods: Osteochondral defects in the medial femoral condyle were created and repaired in 5 mature goats. Postmortem, MRI with T2-mapping and histology were performed. T2 maps were generated and a mean T2 value was calculated for each region of interest. Histologic slides were assessed using MPM with measurements of autocorrelation ellipticity, and by PLM with application of a validated scoring method. Collagen orientation using each of the 3 modalities (T2-mapping, MPM, and PLM) was measured in the center of the repair tissue and compared to remote, normal cartilage.Results: MRI, MPM, and PLM were able to detect a significant difference between repair and normal cartilage (n= 5). The average T2 value was longer for repair tissue (41.43 ± 9.81 ms) compared with normal cartilage (27.12 ± 14.22 ms; P= 0.04); MPM autocorrelation ellipticity was higher in fibrous tissue (3.75 ± 1.17) compared with normal cartilage (2.24 ± 0.51; P= 0.01); the average PLM score for repair tissue was lower (1.6 ± 1.02) than the score for remote normal cartilage (4.4 ± 0.42; P= 0.002). The strongest correlation among the methods was between MRI and PLM (r= −0.76; P= 0.01), followed by MPM and PLM (r= −0.58; P= 0.08), with the weakest correlation shown between MRI and MPM (r= 0.35; P= 0.31).Conclusion: All 3 imaging methods quantitatively measured differences in collagen orientation between repair and normal cartilage, but at very different levels of resolution. PLM is destructive to tissue and requires euthanasia, but because MPM can be used arthroscopically, both T2-mapping and MPM can be performed in vivo, offering nondestructive means to assess collagen orientation that could be used to obtain longitudinal data in cartilage repair studies.