John P. Murray1,2,3, Richard Lartey1,3, Jeehun Kim1,3, Mei Li1,3, Sibaji Gaj1,3, Brendan Eck1,4, Donxing Xie1,3, Carl Winalski1,3,4, Faysal Altahawi3,4, Morgan H. Jones3,5, Bruce M Damon6, Laura J Huston7, Huyen T. Nguyen8, Michael V Knopp8, Kurt P. Spindler3,5, and Xiaojuan Li1,3,4
1Dept. of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States, 2Dept. of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 3Program of Advanced Musculoskeletal Imaging (PAMI), Cleveland Clinic, Cleveland, OH, United States, 4Dept. of Diagnostic Radiology, Imaging Inst., Cleveland Clinic, Cleveland, OH, United States, 5Dept. of Orthopaedic Surgery, Orthopaedics and Rheumatology Inst., Cleveland, OH, United States, 6Dept. of Radiology, Vanderbilt University, Nashville, TN, United States, 7Dept. of Orthopaedics and Rehabilitation, Vanderbilt University, Nashville, TN, United States, 8Dept. of Radiology, Wright Ctr. Of Innovation in BioMed. Imaging, The Ohio State University, Columbus, OH, United States
Synopsis
This is a preliminary report
for the MOON multivendor multisite 10 year follow up using quantitative MR
imaging techniques for patients following ACL reconstruction. Imaging protocol
was harmonized between sites and T1ρ and T2 imaging sequences that were cross-validated between sites
and vendors were applied. Phantom data showed excellent intra-site
repeatability and small inter-site variations. Significantly elevated cartilage
T1ρ and T2 were observed in operated knees
compared to contralateral knees. The preliminary results demonstrated
feasibility of combining multi-site large cohort study with advanced
quantitative MRI, with harmonized protocols and rigorous quality control for
both data acquisition and processing.
Background and Purpose
Patients with Anterior Cruciate Ligament (ACL) injuries have a high risk of developing post-traumatic
osteoarthritis (PTOA) despite ACL reconstruction (ACLR). Previous studies
lacked a long term follow up (over 10 years post-treatment) and large sample
sizes. MRI mapping techniques such as T1ρ and T2 imaging
have been used for detecting early degeneration of soft tissues (such as
articular cartilage) in OA. The goal of this study is to evaluate the joint degeneration
at 10 years after ACLR using quantitative MRI in a large cohort, the
Multicenter Orthopedic Outcomes Network (MOON) onsite cohort.Methods
A total of 209
patients will be studied in this multivendor multisite prospective cohort
study. The patient cohort is the MOON onsite cohort at 10-year after ACLR.
Inclusion/Exclusion criteria for patients include 22-45 years old; ACL tear during
a sport; no previous knee injury at the time of initial enrollment; no graft reconstruction
during follow-up; no history of surgery on the contralateral knee at the time
of initial enrollment. In this preliminary
report, 15 patients (age 35.8±5.4 years; 6 female) were studied at 10 years after ACLR, along with 4 healthy
controls (36.8±11 years; 2 female).
Data were collected from two sites using 3T MR systems (Siemens SkyraFit with a
1Tx/15Rx knee coil and Philips Ingenia with a 1Tx/16Rx knee coil respectively).
The 3D MAPSS T1ρ and T2 imaging sequences have been
previously cross-validated between sites and different MR systems5. The
imaging protocol of the study was harmonized between sites. The imaging
protocol of human subjects included Sag, Cor, Ax turbo-spin-echo (TSE)
morphological imaging, high resolution 3D Dual Echo Steady State (DESS) imaging
(TR/TE=17.55/6.02ms, resolution=0.36x0.46x0.6mm3), 3D MAPSS T1ρ
and T2 imaging (TR/TE=6.51/3.24ms, resolution = 0.44x0.88x4mm3,
spin-lock frequency = 500Hz and time of spin-lock = [0, 10, 40, 70] ms for T1ρ,
Prep TE = [0, 20.064, 40.128, 60.192] ms for T2 imaging). Agarose
gel phantoms (2%, 3%, 4%, weight/volume) were scanned for quality control. Data
were transferred to one site for image quality control and for centralized
quantitative analysis. DESS, T1ρ-weighted,
and T2-weighted images were registered to the first echo of the T1ρ-weighted
images. Cartilage compartments including medial/lateral femoral condyle
(MFC/LFC), medial/lateral tibial plateau (MT/LT), trochlear (TRO), and patellar (PAT) cartilage, were automatically segmented on the registered DESS image by
an in-house deep learning algorithm3 as shown in Figure 1. T1ρ
and T2 maps were obtained by
a voxel-wise two parameter mono-exponential fitting. To evaluate the difference
in T1ρ and T2 between the operated and contralateral
knees, two-tailed paired t-tests were performed under 95% confidence intervals.
Spearman correlation coefficients of T1ρ and T2 values were calculated to investigate
the relationship between the two measures.Results
In phantoms, the intra-site coefficient of variation (CV) of repeated
scans ranged from 0.17-1.16% for T1ρ and 0.11-0.76% for T2
(Table 1), suggesting excellent intra-site repeatability. The inter-site CV
ranged from 3.02-4.02% for T1ρ and 0.22-0.80% for T2
(Table 1), which is within the range of our previous cross-validation study5.
In patients, T1ρ values were significantly
elevated in LFC, LT, MFC and MT, while T2 values were significantly
elevated in MFC, MT and TRO of the operated knees compared to the contralateral knees
(Table 3).
The
Spearman correlation coefficients between T1ρ and T2
values ranged from 0.68-0.95 in contralateral and 0.54-0.95 in operated knees (Table
4). The operated knees tended to have lower correlation between T1ρ
and T2 compared to the contralateral knees.Discussion
Studies on PTOA after ACLR with long term
follow ups (> 10 years) in the literature have been primarily limited to
radiographs and patient reported outcomes. The only MRI study with following
ACLR long term had 7 patient follow ups after 8 years and 2 patient follow ups
after 10 years6. The long-term soft tissue degeneration are largely
unknown in patients after ACLR. The preliminary results of our study showed the
feasibility of combining a multi-site large cohort study with advanced
quantitative MRI, harmonized protocols and rigorous quality control for both
data acquisition and data processing. Our preliminary reports showed excellent
intra-site repeatability and small inter-site variation in phantoms. Traveling
volunteers will be recruited for the study to evaluate the inter-site
variations in human subjects. In patients, significantly elevated T1ρ
and T2 in the operated compared to the contralateral knees was
observed, indicating degeneration in the operated knees. The results are
consistent with reports of shorter-term studies in patients after ACLR7.
Interestingly, although both T1ρ and T2 showed significant differences between the
operated and contralateral knees in the medial side (MFC and MT), only T1ρ,
but not T2, were significantly elevated in the lateral side (LFC and
LT); while in TRO, T2, but not T1ρ, were significantly
elevated. Furthermore, we observed low correlation between T1ρ and T2
in some compartments of the operated knees, such as TRO. These results
suggested that T1ρ and T2 may provide complementary
information related to PTOA development and progression. The findings need to
be confirmed with data collected from more patients. More healthy controls will
be enrolled and compared with both knees from patients. In future analysis, we
will also correlate T1ρ and T2 measures with morphological
lesion grading, and with patient outcomes and functions.Acknowledgements
The study is supported by NIH/NIAMS R01
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