T₂* relaxometry and volume predict semi‐quantitative histological scoring of an ACL bridge‐enhanced primary repair in a porcine model

Abstract

Magnetic resonance imaging (MRI) variables, such as T2* and volume, can predict the healing ligament structural properties. How these MR variables relate to semi-quantitative histology of the healing ACL is yet unknown. We hypothesized that T2* and volume would predict the histological scoring of a healing ACL. Yucatan minipigs underwent ACL transection and received: bridge-enhanced ACL repair or no treatment. The surgical legs were harvested after 52 weeks and imaged using a high resolution 2-echo sequence. For each ligament the volume and median T2* values were determined. The ACL specimens were then histologically analyzed using the advanced Ligament Maturity Index (LMI). The T2* of the healing ligaments significantly predicted the Total LMI score as well as the Cell, Collagen and Vessel sub-scores; R2=0.78, 0.67, 0.65, and 0.60, respectively (p≤0.001). The ligament volume also predicted the Total LMI score, Cell and Collagen sub-scores; R2=0.39, 0.33, 0.37, and 0.60, respectively (p≤0.001). A lower ligament T2* or a higher volume was associated with higher histological scores of the healing ligaments. This study provides a critical step in the development of a noninvasive method to evaluate ligament healing on a microscopic scale.

Cartilage Damage Is Related to ACL Stiffness in a Porcine Model of ACL Repair

“…that the median T 2 * relaxation of healing ACL after surgery falls within the range of 7-16 ms, 14 which can be nearly twice as long as the median T 2 * of intact ligament at 8.5 ± 0.6 ms. 13 Furthermore, we have shown that these relaxation times correlate with semi-quantitative histology measures. 49 The increase in median ACL T 2 * relaxation times in Figure 1B corroborates the findings of these earlier studies. We therefore believe that the gradient echo sequence described here is well-suited for capturing relevant changes in MR T 2 * relaxation times that are characteristic of healing ligament within 6 months after ACL repair.…”

“…While UTE sequences have demonstrated sensitivity to changes in intact tendon and ligament ultrastructure with measured T 2 * relaxation times on the order of 3–14.8 ms, we have previously shown that the median T 2 * relaxation of healing ACL after surgery falls within the range of 7–16 ms, which can be nearly twice as long as the median T 2 * of intact ligament at 8.5 ± 0.6 ms . Furthermore, we have shown that these relaxation times correlate with semi‐quantitative histology measures . The increase in median ACL T 2 * relaxation times in Figure B corroborates the findings of these earlier studies.…”

Sensitivity of ACL volume and T 2 ∗ relaxation time to magnetic resonance imaging scan conditions

“…To investigate the extent that T 2 * relaxation times were sensitive to the more clinically applicable scan conditions versus the conditions that we have used previously in our research (Biercevicz, et al, 2015; Biercevicz, et al, 2014), T 2 * relaxation times derived from in vivo 384×384 matrix resolution were compared to those derived from in situ 512×512 matrix resolution scan conditions. Scanning ACLs at high resolution in situ within 60 minutes of euthanasia led to decreased and more variable T 2 * relaxation times compared to in vivo moderate resolution scans.…”

“…T 2 * is a measure of MR signal relaxation that is related to the degree of free water bound by collagen (Helms, et al, 2008), with highly organized collagen structures yielding shorter T 2 * relaxation times (Williams, et al, 2012). T 2 * is particularly well suited for imaging ligament and tendon healing in vivo because collagen re-organization is of interest (Biercevicz, et al, 2015; Weiler, et al, 2001). We have previously demonstrated that a larger volume of the anterior cruciate ligament (ACL) containing short MR T 2 * relaxation times predicts the ligament structural properties in a minipig model of bridge-enhanced ACL repair (Biercevicz, et al, 2014).…”

“…In other words, the binned sub-volume describes how much of the ACL is composed of highly organized collagen (which can account for more than 25% of the total ligament volume), and the T 2 * first quartile describes tissue quality and variation within the ACL and is dependent on the values contained within the dataset. Both volume and quality are central elements of our models to predict healing ACL structural properties (Biercevicz, et al, 2013; Biercevicz, et al, 2015; Biercevicz, et al, 2014). In order to extend the in situ-based prediction models to in vivo conditions, we sought to determine whether intact ACL total volume and T 2 * relaxation times were sensitive to MR imaging scan conditions by: 1) determining the sensitivity of ACL volume and T 2 * relaxation time to MR scan resolution, and 2) exploring whether ACL volume and T 2 * relaxation times were different when measured in vivo, in situ or ex vivo after a freeze-thaw cycle in the minipig model.…”