Matthew Grondin1, Fang Liu2, Sami Faruqui2, Alexei Samsonov2, Wan-Ju Li3, Corinne Henak1, and Richard Kijowski2
1Mechanical Engineering, University of Wisconsin-Madison, Madison, WI, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States, 3Orthopedic Surgery, University of Wisconsin-Madison, Madison, WI, United States
Synopsis
Multi-component Driven Equilibrium Single Pulse
Observation of T1 and T2 (mcDESPOT) was used to measure single-component T2
relaxation time (T2Single) and the fraction of the fast relaxing
macromolecular bound water component (FF) of 24 human patellar
cartilage samples at 3.0T. The cartilage
samples underwent mechanical testing to measure linear modulus and energy dissipation
and biochemical analysis to measure proteoglycan content. There were significant (p<0.01) and moderate positive
correlations between FF and proteoglycan content, linear modulus, and
energy dissipation of cartilage. There
were non-significant (p=0.06-0.21) and low negative correlations between T2Single
and proteoglycan content, linear modulus, and energy dissipation of cartilage.
Introduction
Multi-component Driven Equilibrium
Single Pulse Observation of T1 and T2 (mcDESPOT) is a rapid method for
bi-component T2 mapping of the articular cartilage of the human knee joint at
3.0T, which can measure single-component T2 relaxation time (T2Single),
the T2 relaxation times of the fast relaxing macromolecular bound (T2F)
and slow relaxing bulk (T2S) water components, and the fraction of
the fast relaxing macromolecular bound water component (FF).1,2,3 Previous
studies have shown that FF is the bi-component T2 parameter with the
highest sensitivity for detecting cartilage degeneration within the human knee
joint.2,3 This study was
performed to determine whether T2Single and FF measured
using mcDESPOT at 3.0T could provide information regarding the proteoglycan
content and mechanical properties of human patellar cartilage.Methods
Five
patellar specimens were harvested from fresh frozen human cadaveric knees. The
specimens were placed in a container filled with phosphate-buffered solution and
imaged on a 3.0T scanner (Discovery MR750, GE Healthcare; Waukesha, WI) using a
single-channel wrist coil (Mayo Clinic, Rochester, MN). Spoiled gradient echo
(SPGR) scans were acquired with TR/TE=7.2/2.9ms over a range of flip angles (α
=3, 4, 5, 6, 7, 9, 13, 18°). Two fully-balanced steady-state free
precession (bSSFP) scans with radiofrequency phase cycling on and off were
acquired with TR/TE=6.6/3.2ms over a range of flip angles (α=2, 5, 10, 15, 20,
30, 40, 50°). An inversion recovery IR-SPGR scan with TR/TE=7.2/2.9ms,
TI=450ms, and α=5° was also acquired. All scans were performed in the sagittal
plane with a 14cm field of view, 700 x 240 matrix, 2mm slice thickness, and one
excitation. Patellar cartilage T2Single
and FF maps were reconstructed in MATLAB (MathWorks, Natick, MA) using
the mcDESPOT model.1,2 Mean cartilage
T2Single and FF was measured in the exact same locations
on the patellar specimens where 24 cartilage samples were extracted (Figure
1). The 24 cartilage samples underwent unconfined
compression under cyclic displacement to 10% strain at 0.01Hz on a test machine
(3230-AT, TA Instruments, Eden Prairie, MN) to measure linear modulus and energy
dissipation. A subset of 17 cartilage
samples underwent biochemical analysis with proteoglycan glycosaminoglycan (GAG)
content measured using the
AMSBIO Proteoglycan Detection Kit (#280560-N, AMSBIO Biotechnology, Abingdon,
UK). Pearson correlation
coefficients were used to compare T2Single and FF and the
proteoglycan content, linear modulus, and energy dissipation of the cartilage
samples. Results
mcDESPOT acquired high-resolution cartilage T2Single
and FF maps of the patellar cartilage specimens (Figure 2). There was a significant and moderate positive
correlation between FF and proteoglycan content (r=0.605 and p=0.007). There was a low and non-significant negative
correlation between T2Single and
proteoglycan content (r=-0.310 and p=0.21) (Figure 3). There were moderate and significant
positive correlations between FF and linear modulus (r=0.638 and
p<0.001) and energy dissipation (r=0.657 and p<0.001) (Figure 4). There were low and non-significant negative
correlations between T2Single and linear modulus (r=0.-409 and
p=0.06) and energy dissipation (r=-0.383 and p=0.07) (Figure 5).Discussion
Nuclear magnetic resonance (NMR) spectroscopy has identified three water
components within cartilage: water tightly bound to collagen, water tightly
bound to proteoglycan, and bulk water loosely bound to the macromolecular
matrix with T2 relaxation times of 2.3ms, 25.2ms, and 96.3ms respectively.4 The first echo of mcDESPOT is too short
to capture signal from collagen bound water.
Thus, the fast relaxing macromolecular bound water component of
cartilage measured using mcDESPOT, with a T2F ranging between 13.6ms
and 22.3ms, likely represents water tightly bound to proteoglycan.1 Our study confirmed this hypothesis and showed
a significant (p=0.007) positive correlation between FF measured
using mcDESPOT and the proteoglycan
content of cartilage. Our study also found significant (p<0.001) positive
correlations between FF and the linear modulus and energy dissipation
of cartilage, which are mechanical properties primarily influenced by
proteoglycan within cartilage. Previous studies
using NMR spectroscopy have also documented significant (p<0.05) positive
correlations between the fraction of proteoglycan bound water and the proteoglycan
content 4,5 and mechanical properties 6 of cartilage. However,
these studies have used Carr-Purcell-Meiboom-Gill sequences with extremely long
scan times for single slice evaluation of ex-vivo cartilage samples on 9.7T NMR
scanners.4,5,6 In contrast, mcDESPOT
can perform three-dimensional bi-component T2 mapping of the articular
cartilage of the human knee joint at 3.0T with high spatial resolution, large
volume coverage, and clinically feasible scan times. Our study found non-significant (p=0.06-0.21)
negative correlations between T2Single measured using mcDESPOT and
the proteoglycan content, linear modulus, and energy dissipation of
cartilage. This is likely due to the
fact that T2Single is a composite measure reflecting the T2 relaxation times of all water components of cartilage and thus has limited
specificity to any individual water component.
A previous study has shown that FF is superior to T2Single
for distinguishing between normal and degenerative cartilage within the human
knee joint.2 Our study found that FF had stronger correlations with the proteoglycan content, linear modulus, and energy dissipation of cartilage than T2Single,
which provides further evidence of the advantages of performing bi-component T2 mapping of cartilage. Conclusions
FF measured using mcDESPOT at 3.0T showed significant (p<0.01) and moderate positive correlations with the proteoglycan content, linear modulus, and energy dissipation of human patellar cartilage and may potentially serve as a new
biomarker for proteoglycan within cartilage.Acknowledgements
Research support provided by GE Healthcare,
University of Wisconsin Institute of Clinical and Translational Research, and
NIAMS grant R01-AR068373.References
(1) Liu F, Chaudhary R, Hurley S, et al. Rapid multicomponent T2 analysis
of the articular cartilage of the human knee joint at 3.0T. J Magn Reson Imaging.
2014; 39(5):1191-1197.
(2) Liu F, Choi K, Samsonov A,
et al. Articular cartilage of the human knee joint: In
vivo multi-component T2 analysis at 3.0 T. Radiology. 2015; 277(2):477-488.
(3) Kaiser J, Vignos MF, Liu F, et
al. MRI assessments of cartilage
mechanics, morphology and composition following reconstruction of the anterior
cruciate ligament. Clin Biomech. 2016; 34:38-44.
(4) Reiter D, Lin P, Fishbein K, et
al. Multi-component T2 relaxation
analysis in cartilage. Magn Reson Med. 2009; 61(4):803-809.
(5) Reiter D,
Roque R, Lin P, et al. Mapping proteoglycan-bound water in
cartilage: Improved specificity of matrix assessment using multi-exponential
transverse relaxation analysis. Magn Reson Med. 2009; 62(5):1311-1318.
(6)
Irrechukwu O, Von Thaer S, Frank E, et al. Prediction of cartilage
compressive modulus using multi-component analysis of T2 relaxation data and
support vector regression. NMR Biomed. 2014; 27(4):468-477.