Quantitative Assessment of In Vivo Human Anterior Cruciate Ligament Autograft Remodeling: A 3-Dimensional UTE-T2* Imaging Study

Abstract

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.

Anterior cruciate ligament autograft maturation on sequential postoperative MRI is not correlated with clinical outcome and anterior knee stability

“…The most important findings of our study were that an ACL autograft is undergoing a significant transformation process during the first 2 years postoperatively which is consistent with the previously described ligamentization process [9,20,45]. These findings confirmed our first hypothesis that an ACL graft exhibits a high MRI signal intensity 6 months after surgery but approximates the MRI appearance of a native ACL at 1-and 2 years postoperatively.…”

Can we afford to ignore the biology of joint healing and graft incorporation after ACL reconstruction?

“…The individual patient curves suggest greater remodeling activity in some patients between 6 months and 1 year than others. Similar MRI UTE‐T2* findings over the 1st year after ACLR were independently reported 1 year later by Warth et al 67 who used a radial UTE sequence on a third MRI system. Chu and Williams 31 extended UTE‐T2* evaluation of ACL grafts through 2 years after ACLR where observation of a decrease in ACL graft UTE‐T2* between 1 and 2 years follow‐up in two separate patient cohorts suggests continued graft maturation during this time frame.…”

“…Limited biopsy studies and several newer MRI studies, however, show a longer graft maturation timeline in humans than that of rabbits and sheep 31,63–67 . In a review of human biopsy studies, Claes et al 64 found just four studies meeting inclusion criteria.…”

“…Limited biopsy studies and several newer MRI studies, however, show a longer graft maturation timeline in humans than that of rabbits and sheep. 31,[63][64][65][66][67] In a review of human biopsy studies, Claes et al 64 found just four studies meeting inclusion criteria. These few human biopsy studies are descriptive and depict a variable, lengthy, and incomplete maturation process irrespective of graft type.…”

Regional Differences in Anterior Cruciate Ligament Signal Intensity After Surgical Treatment

“…[14][15][16][17]21 Other studies have used the ACL signal intensity (ie, median or mean) across the 3dimensional geometry of the ACL. 4,13,20,26 However, little is known about signal variations across the ACL and how they may influence MR-based assessments of ACL healing. Previous experimental reports on regional variations in native ACL mechanical properties (eg, differences between ACL bundles) 8,9,23,24 have highlighted the possibility of regional differences in MR image signal across the ACL.…”