The development of noninvasive in vivo imaging-based biomarkers indicative of the ACL microstructure is of utmost clinical interest, as this might allow for conclusions about its mechanical properties and stress tolerance to be drawn. Such a tool would also be applicable to the assessment of the healing process following ACL reconstruction. One possible approach to obtaining such biomarkers that has received increased attention in the past decade relies on the MRI-based T2* mapping technique [12, 14,15,16,17]. T2* relaxation times are characteristic values that provide quantitative information about the tissue structure and composition, in particular the collagen fibre content and organisation, on a voxel-by-voxel basis. Aiming to provide evidence indicative of a weakening of the ACL structure that might promote fatigue tears and explain a potential accumulation of injuries in the later stages of the competitive season, we applied the T2* mapping technique to longitudinally study three professional alpine ski racers over the course of an entire season. The main finding of our pilot experiments is that T2* values as measured under different loading conditions peak in April, corresponding with the end of the competitive season in alpine ski racing.
In one of the first studies proposing T2* for the evaluation of the structure (and tensile properties) of the ACL, Biercevicz et al. [16] used a porcine model and found the volume and median greyscale in T2*-weighted images to predict the maximum failure load of patellar tendon allografts used for ACL reconstruction. Since signal intensities are sequence- and magnet-dependent [18], the same group then proceeded to refine the technique and use T2* relaxation times, which were found to correlate well with the results of tensile failure tests and the histologically assessed ligament maturity index of repaired minipig ACLs [14, 15]. According to these studies, lower T2* values coincide with greater stress tolerance and ligament maturity. Validation in human cadavers has proven to be more challenging, which may be due to the restricted variability of T2* relaxation times measured in cadaveric ligaments [17]. The joint body of evidence published to date, however, suggests that T2* mapping is a promising tool for the in vivo evaluation of ACL quality. This notion is also supported by a recent report testifying to excellent intra-rater (intraclass correlation coefficient 0.98) and inter-rater reliability (intraclass correlation coefficient 0.90) of T2* values measured in the ACL [19].
At rest, the T2* times measured in our study ranged between 8.4 and 16.9 ms in the central and between 8.0 and 15.5 ms in the femoral ACL region. These values agree well with those reported by Anz et al. [19] but are slightly lower than those found by Schmitz et al. [12], who reported ranges of 15.9–25.1 ms and 13.9–30.6 ms, respectively, in recreationally active men of similar age. Differences in the image acquisition protocol may explain the discrepant findings. Since Schmitz et al. [12] obtained the first echo only after 8.3 ms (the shortest TE used in our study was 3.7 ms), the shape of their signal intensity decay curve may have appeared with a different shape, thus yielding longer T2* times. Of note, our preliminary study was the first to measure T2* in the strained ACL. During the application of pressure, T2* values were greater by up to 33% and 20% in the central and femoral region of the ACL, respectively.
Stress MRI examinations have been performed in knee articular cartilage [20, 21]. These studies showed small, yet statistically significant load-associated decreases in T2 relaxation times, which were explained by cartilage compression and extrusion of water, leading to a more compressed collagen and proteoglycan structure. The stress tests performed in our study, by contrast, acted to extend the ACL. Thus, it is plausible to assume that the density of collagens and other solid ACL components was lower during pressure application, resulting in the observed increase in T2* values.
The primary findings of this study are the seasonal changes of T2* relaxation times in our sample of professional alpine ski racers that were most pronounced in the central region of the ACL and could be observed both at rest and during application of pressure. While average T2* values remained fairly constant between the measurements obtained in October and January, there was a marked increase of 41% (resting measurements) between January and April. Longer ACL T2* relaxation times have been associated with lower cell density and collagen organisation [15] and tensile load to failure [14]. Acknowledging the small sample size and explorative nature of the study, our data are, therefore, indicative of decreased ACL stress tolerance capacity in the end phase of the competitive season. The subsequent decrease of T2* values between April and July (-19%) might be interpreted as a partial recovery of the ACL structure. Further studies involving larger samples are required to substantiate these hypotheses.
This pilot study is subject to a number of limitations. First and foremost, the small sample size (n = 3) precluded us from performing inferential statistics, which is why our results must be considered preliminary. However, it should be pointed out that a substantial increase in T2* values between January and April was consistently observed in all three subjects. In addition, implausibly bright spots presumably resulting from magic angle artefacts [13] precluded the analysis of T2* values in the ACL proximal third. Furthermore, no direct measures of the ACL mechanical properties could be obtained, so the postulated correlation of T2* values with the ligament stress tolerance relies solely on findings from earlier studies in animals [14, 15]. Future studies might consider including stress imaging. Finally, it must be mentioned that, although T2* maps were coregistered with high-resolution images to warrant consistent in-plane ROI placement, minor differences due to not perfectly matched slices cannot be ruled out.
In conclusion, the results of this preliminary study show seasonal changes of T2* values mapped in the ACL of professional alpine ski racers, which are most pronounced in the ligament's central region. The values were found to peak in April, which coincides with the end of the competitive season and may reflect a decrease in stress tolerance, potentially increasing the risk of fatigue tears. Further research in larger samples is required.