Marianne S. Black1,2, Katherine A. Young2, Akshay S. Chaudhari2,3, Bragi Sveinsson4, Feliks Kogan2, Uchechukwuka Monu2,5, Emily J. McWalter6, Marc E. Levenston1,2,3, Garry E. Gold2, and Brian A. Hargreaves2,3,5
1Mechanical Engineering, Stanford University, Stanford, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Bioengineering, Stanford University, Stanford, CA, United States, 4Radiology, Massachusetts General Hospital, Boston, MA, United States, 5Electrical Engineering, Stanford University, Stanford, CA, United States, 6Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada
Synopsis
T2-mapping can be used to detect changes in cartilage
following ACL injury that are indicative of cartilage degeneration. We imaged
subjects at 3-weeks and 3-months post-ACL-reconstruction surgery to obtain T2 relaxation
times for the femoral cartilage of both knees. A trend in increasing T2 relaxation
times was observed for the injured knee at 3-months relative to 3-weeks,
although this increase was not significant, while T2 remained consistent for
the contralateral knee in this time. This work demonstrates that changes to
cartilage may be occurring earlier than expected in the injured knee following
ACL-reconstruction surgery.
Purpose
Patients who have experienced anterior cruciate ligament (ACL)
tears have a significantly elevated risk of developing osteoarthritis, whether surgically
reconstructed or not1,2. Quantitative MRI measures, such as T2,
which is considered reflective of collagen content and organization3 have been
used to track changes in cartilage following ACL injury4,5. At 1-year
post-ACL-reconstruction, elevations in T2 times have been observed5.
It is desirable to observe the earliest signs of cartilage degeneration
in ACL injured patients to allow for the development and application of early
interventional treatments to prevent further cartilage changes. The objective
of this study was to determine if changes in T2 can be detected 3-months post-ACL-reconstruction
surgery.Methods
We scanned the ACL-reconstructed and contralateral knees of 5
subjects (4 females, ages 26-54) as part of a larger on-going study of 30
subjects over 2-years at a 3T MR scanner (GE Healthcare, Milwaukee, WI) using a
16-channel flexible knee coil. Subjects were excluded if they had a history of
knee injury or surgery in the contralateral knee, a concomitant PCL tear in
their ACL-injured knee, or a BMI > 35. Subjects were scanned 3-weeks and 3-months following surgery using a double-echo in steady-state sequence (DESS) in
the sagittal plane with scan parameters: FOV=160mm, matrix=384x320, TE1/TE2/TR=6,
38, 22ms, slice thickness=1.5mm, flip angle=25°. T2 values
were calculated from the two DESS echoes using a simple analytical model6
(Fig 1). The femoral cartilage was manually segmented from the sum-of-squares
of the two DESS echoes (Seg3D, University of Utah). Segmented masks were then
further automatically divided into the patellofemoral groove, medial condyle and
lateral condyle. Differences between average T2 at 3-weeks and 3-months and
differences between ACL-reconstructed and contralateral knees were compared using
a general linear model (α<0.05).Results
The average
T2 in the femoral cartilage of ACL-reconstructed knees in all subjects increased
from 3 weeks (average T2=33.4ms) to 3 months post-surgery (average T2=35.2ms) in the
injured knee by 1.8ms, however it was not statistically significant. No
significant change was observed in the contralateral knees in this same time,
and the average T2 difference between 3 weeks (average T2=32.9) and 3 months
(average T2=32.7ms) was only 0.2ms (Fig 2). The interaction between
post-surgical time-point and knee (ACL-reconstructed or contralateral) did not
reach significance in the general linear model (p=0.087). At 3 weeks post-op, there was little difference
in T2 relaxation times between the injured and contralateral knee, but at 3
months post-op the T2 values of the injured knee were higher than in the
contralateral knee by 2.4ms, which also was not significant (Fig 2). Looking
individually at subjects, ACL-reconstructed knees showed an increase in T2
times from 3 weeks to 3 months in 4 out of 5 subjects (Fig 3).Discussion
We observed a trend of increasing T2 relaxation times from 3-weeks
to 3-months post-surgery for ACL-reconstructed knees, whereas T2 relaxation times
in contralateral knees were consistent between these time points. We have
previously shown that our DESS T2 measurements are repeatable within a 3%
coefficient of variation6. T2 elevations 3-months post-surgery are
consistent with the small increases previously seen in T2 times 1-year
post-ACL-reconstruction5, suggesting that the changes in cartilage
leading to elevated T2 may be occurring much earlier following
ACL-reconstruction surgery than expected. The difference in T2 between healthy
and osteoarthritic femoral cartilage in one year has been shown to be approximately
5ms8.9, which is just over 2x the difference in T2 times we saw in
our study in under 3-months. Changes to T2 between 3 weeks and 3 months
post-surgery could also be an effect of a subject’s modified mobility and reduced weight-bearing of the injured knee at these times, or a result of
post-surgical inflammation. Patients are still relying on crutches 3-weeks
post-surgery and are then walking 3-months post-surgery. These early changes in
T2 may be indicative of degenerative changes occurring in the cartilage of the
ACL-reconstructed subjects, but a larger sample size of ACL-reconstructed
subjects and long-term follow-up of these subjects will be necessary to
understand if these early changes are correlated with osteoarthritis. Being
able to identify when the earliest degenerative cartilage changes occur can
allow for the development and application of interventional osteoarthritis
treatments aimed at preventing further cartilage degeneration.Conclusion
Femoral cartilage T2 relaxation times increasing from 3-weeks
to 3-months post-surgery for ACL injured subjects suggest that degenerative
cartilage changes may be happening within 3-months of ACL reconstruction surgery.
Additional subjects are in the process of being recruited and will help further
elucidate trends in cartilage T2 relaxation times following ACL-reconstruction
surgery.Acknowledgements
NIH R01 AR0063643, NIH R01
EB002524, NIH K24 AR062068, and GE Healthcare.References
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