Quantitative Assessment of In Vivo Human Anterior Cruciate Ligament Autograft Remodeling: A 3-Dimensional UTE-T2* Imaging Study
Authors: Warth Ryan J. , Zandiyeh Payam , Rao Mayank , Gabr Refaat E. , Tashman Scott , Kumaravel Manickam , Narayana Ponnada A. , Lowe Walter R. , Harner Christopher D. 
Published: September 2020

Background: The timing of return to play after anterior cruciate ligament (ACL) reconstruction is still controversial due to uncertainty of true ACL graft state at the time of RTP. Recent work utilizing ultra-short echo T2* (UTE-T2*) magnetic resonance imaging (MRI) as a scanner-independent method to objectively and non-invasively assess the status of in vivo ACL graft remodeling has produced promising results. Purpose/Hypothesis: The purpose of this study was to prospectively and noninvasively investigate longitudinal changes in T2* within ACL autografts at incremental time points up to 12 months after primary ACL reconstruction in human patients. We hypothesized that (1) T2* would increase from baseline and initially exceed that of the intact contralateral ACL, followed by a gradual decline as the graft undergoes remodeling, and (2) remodeling would occur in a region-dependent manner. Study Design: Case series; Level of evidence, 4. Methods: Twelve patients (age range, 14-45 years) who underwent primary ACL reconstruction with semitendinosus tendon or bone–patellar tendon–bone autograft (with or without meniscal repair) were enrolled. Patients with a history of previous injury or surgery to either knee were excluded. Patients returned for UTE MRI at 1, 3, 6, 9, and 12 months after ACL reconstruction. Imaging at 1 month included the contralateral knee. MRI pulse sequences included high-resolution 3-dimensional gradient echo sequence and a 4-echo T2-UTE sequence (slice thickness, 1 mm; repetition time, 20 ms; echo time, 0.3, 3.3, 6.3, and 9.3 ms). All slices containing the intra-articular ACL were segmented from high-resolution sequences to generate volumetric regions of interest (ROIs). ROIs were divided into proximal/distal and core/peripheral sub-ROIs using standardized methods, followed by voxel-to-voxel registration to generate T2* maps at each time point. This process was repeated by a second reviewer for interobserver reliability. Statistical differences in mean T2* values and mean ratios of T2*inj/T2*intact (ie, injured knee to intact knee) among the ROIs and sub-ROIs were assessed using repeated measures and one-way analyses of variance. P < .05 represented statistical significance. Results: Twelve patients enrolled in this prospective study, 2 withdrew, and ultimately 10 patients were included in the analysis (n = 7, semitendinosus tendon; n = 3, bone–patellar tendon–bone). Interobserver reliability for T2* values was good to excellent (intraclass correlation coefficient, 0.84; 95% CI, 0.59-0.94; P < .001). T2* values increased from 5.5 ± 2.1 ms (mean ± SD) at 1 month to 10.0 ± 2.9 ms at 6 months ( P = .001), followed by a decline to 8.1 ± 2.0 ms at 12 months ( P = .129, vs 1 month; P = .094, vs 6 months). Similarly, mean T2*inj/T2*intact ratios increased from 62.8% ± 22.9% at 1 month to 111.1% ± 23.9% at 6 months ( P = .001), followed by a decline to 92.8% ± 29.8% at 12 months ( P = .110, vs 1 month; P = .086, vs 6 months). Sub-ROIs exhibited similar increases in T2* until reaching a peak at 6 months, followed by a gradual decline until the 12-month time point. There were no statistically significant differences among the sub-ROIs ( P > .05). Conclusion: In this preliminary study, T2* values for ACL autografts exhibited a statistically significant increase of 82% between 1 and 6 months, followed by an approximate 19% decline in T2* values between 6 and 12 months. In the future, UTE-T2* MRI may provide unique insights into the condition of remodeling ACL grafts and may improve our ability to noninvasively assess graft maturity before return to play.