Ashley A. Williams1, Nicholas P Drain2, Yongxian Qian3, Kathryn J. Stevens4, and Constance R. Chu1
1Orthopaedic Surgery, Stanford University, Stanford, CA, United States, 2Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States, 3Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, 4Department of Radiology, Stanford University, Stanford, CA, United States
Synopsis
Keywords: Osteoarthritis, Relaxometry, UTE-T2*, meniscus, radiography
This study examines whether
compositional degeneration of the meniscus is a potential predictor of future radiographic
knee OA. Mensical UTE-T2* maps acquired
prior to anterior cruciate ligament reconstruction (ACLR) were compared to knee
radiographs collected 11 years later in 11 ACLR patients. On average, pre-operative posterior
medial and lateral meniscal UTE-T2* values were 39% and 33% higher in knees
with KL grade ≥ 2 compared to knees with KL grades
0-1 at 11-year follow-up
(p=0.016,
0.034). Thus, elevated meniscal UTE-T2*
in the context of an ACLR knee may be a warning of increased risk for
radiographic osteoarthritis many years later.
PURPOSE
Although anterior
cruciate ligament reconstruction (ACLR) restores knee stability following an
ACL tear, approximately 50% of ACLR patients develop knee osteoarthritis (OA)
within 10 to 15 years of injury.1; 2 ACL tears are often accompanied by trauma to
the posteromedial and posterolateral menisci (pMM, pLM) which are the secondary
restraints to anterior tibial translation and combined axial and rotary loads,
respectively.3 Ultrashort echo
time-enhanced T2* (UTE-T2* mapping) is sensitive to subsurface injury and
degeneration of the pMM and pLM following ACL tear, even in the absence of
frank meniscal tears or clinically detectable meniscus pathology.4; 5 However, the
degree to which compositional changes of the menisci are associated with
long-term knee OA has not been investigated. This study examines whether compositional
degeneration of the meniscus is a potential predictor of future knee OA. We hypothesize that
higher meniscal UTE-T2* values measured after ACL injury will be associated
with a greater prevalence of radiographic OA6; 7 10+ years after ACLR. METHODS
UTE-T2*
relaxation was measured in the menisci of 30 ACL-deficient participants (17
females; mean age: 31 (SD: 9) years, mean BMI: 28 (SD: 6) kg/m2)
within 40 days prior to reconstruction surgery. Radiographs of the
lower limbs were obtained 10-12 years post-ACLR. Participants
provided written consent for both the initial4 and follow-up IRB-approved studies. MRI T2* images
were acquired with a 3-D AWSOS (Acquisition-Weighted Stack of Spirals)8 sequence using a 3T scanner (Siemens) and an
8-channel knee coil (Invivo, Gainsville, FL) at 11 TEs ranging 0.6-40 ms were
collected as previously reported.4 Pixel-by-pixel mono-exponential T2* fits were
generated with MRIMapper software (© Beth Israel Deaconess and MIT 2006). Two regions of interest (ROIs) were manually
segmented on each of 2 single sections from the centers of the medial and
lateral compartments of the knee to include the anterior and posterior horns of
the medial and lateral menisci (aMM, pMM, aLM, pLM), Figure 1. Mean UTE-T2* values were averaged across all
voxels within the ROI. Kellgren-Lawrence (KL)6 scoring of
follow-up radiographs was performed by a musculoskeletal radiologist. Normality
of all data sets was assessed by Shapiro-Wilk tests. UTE-T2* values in participants with x-ray
scores KL 0-1 were compared to those of participants with KL scores ≥ 2 (definite
osteophytes) with t-tests (or Mann-Whitney U tests). Statistical analyses were
performed with SPSS (v25, IBM); significance was accepted for p < 0.05.RESULTS
UTE-T2* prediction of radiographic OA at 11 years post ACLR. Follow-up x-rays were collected in 11/30 participants at 11 years (11.4
(95%CI: 11.0, 11.8) years) after ACLR (6 females; mean age: 30 (SD: 11) years,
mean BMI: 26 (SD: 5) kg/m2).
Five participants were found to have radiographic OA (KL ≥ 2) of their
ACLR knee, while 6 participants did not (KL 0-1). On average, pre-operative
posterior medial and lateral meniscal UTE-T2* values were 39% and 33% higher in
knees with KL grade ≥ 2 compared
to knees with KL grades 0-1 at 11-year follow-up (p=0.016, 0.034), Figure 2. Neither age nor BMI differed by KL group (p>0.7). Medial meniscal tears were present at the
time of ACLR in 3/5 participants with KL ≥
2 and 1/6 participants with KL 0-1. Between ACLR and 11-yr follow-up, 2
participants, one in each KL group, reported re-injury to their ACLR knee but
neither required additional surgery. Anterior medial and lateral meniscal
UTE-T2* values did not differ by KL group (p>0.7).DISCUSSION
Meniscus UTE-T2* measured prior to ACLR predicted
radiographic OA prevalence 11 years later in a small cohort of patients. Significantly
elevated UTE-T2* values, indicating
compositional degeneration of the subsurface substance4; 5; 10 of the posterior horns of both the medial and
lateral menisci, were detected in knees demonstrating KL grade ≥ 2 compared to
knees without radiographic evidence of OA. Development of radiographic OA
following ACLR in knees with torn menisci is thought to be mediated by inadequate
transmission of contact forces11; 12 and also by alteration of normal biologic
activities within the menisci including upregulation of enzymes and
inflammatory mediators capable of damaging the adjacent cartilage.13 While the mechanistic relationship between compositional meniscus degeneration,
especially in grossly intact menisci, and the bony changes characteristic of
radiographic OA remains to be elucidated, both mechanical and biologic factors may
contribute to osseous remodeling. CONCLUSION
The results from this
study support the interpretation of elevated meniscal UTE-T2* in the context of
an ACLR knee as a sign of pre-OA and a warning of increased risk for
radiographic osteoarthritis many years later.Acknowledgements
NIH
RO1 AR052784 (PI – CR Chu) and DOD W81XWH-18-1-0590 (PI-CR Chu).References
1. Barenius
B, Ponzer S, Shalabi A, et al. 2014. Increased risk of osteoarthritis after
anterior cruciate ligament reconstruction: a 14-year follow-up study of a
randomized controlled trial. Am J Sports Med 42(5):1049-1057.
2. Lohmander
LS, Englund PM, Dahl LL, et al. 2007. The long-term consequence of anterior
cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med
35(10):1756-1769.
3. Musahl
V, Citak M, O'Loughlin PF, et al. 2010. The effect of medial versus lateral
meniscectomy on the stability of the anterior cruciate ligament-deficient knee.
Am J Sports Med 38(8):1591-1597.
4. Chu
CR, Williams AA, West RV, et al. 2014. Quantitative Magnetic Resonance Imaging
UTE-T2* Mapping of Cartilage and Meniscus Healing After Anatomic Anterior
Cruciate Ligament Reconstruction. Am J Sports Med 42(8):1847-1856.
5. Williams
A, Qian Y, Golla S, et al. 2012. UTE-T2 * mapping detects sub-clinical meniscus
injury after anterior cruciate ligament tear. Osteoarthritis Cartilage 20(6):486-494.
6. Kellgren
JH, Lawrence JS. 1957. Radiological assessment of osteo-arthrosis. Ann Rheum
Dis 16(4):494-502.
7. Schiphof
D, Boers M, Bierma-Zeinstra SM. 2008. Differences in descriptions of Kellgren
and Lawrence grades of knee osteoarthritis. Ann Rheum Dis 67(7):1034-1036.
8. Qian
Y, Boada FE. 2008. Acquisition-weighted stack of spirals for fast
high-resolution three-dimensional ultra-short echo time MR imaging. Magn Reson
Med 60(1):135-145.
9. Brown
G, Amendola A. 2012. Radiographic Evaluation and Preoperative Planning for High
Tibial Osteotomies. Oper Tech Sports Med 20:93-102.
10. Juras
V, Apprich S, Zbyn S, et al. 2014. Quantitative MRI analysis of menisci using
biexponential T2* fitting with a variable echo time sequence. Magn Reson Med
71(3):1015-1023.
11. Jones
MH, Spindler KP. 2017. Risk factors for radiographic joint space narrowing and
patient reported outcomes of post-traumatic osteoarthritis after ACL
reconstruction: Data from the MOON cohort. J Orthop Res 35(7):1366-1374.
12. Nordenvall
R, Bahmanyar S, Adami J, et al. 2014. Cruciate ligament reconstruction and risk
of knee osteoarthritis: the association between cruciate ligament injury and
post-traumatic osteoarthritis. a population based nationwide study in Sweden,
1987-2009. PLoS One 9(8):e104681.
13. Riordan
EA, Little C, Hunter D. 2014. Pathogenesis of post-traumatic OA with a view to
intervention. Best Pract Res Clin Rheumatol 28(1):17-30.