Yanping Xue1,2, Yajun Ma1, Zhao Wei1, Francis Tang1, Mei Wu1, Saeed Jerban1, Eric Y Chang1,3, and Jiang Du1
1University of California, San Diego, San Diego, CA, United States, 2Radiology, Beijing Chao-Yang Hospital, Beijing, China, 3VA San Diego Healthcare System, San Diego, CA, United States
Synopsis
Quantitative MRI biomarkers, such as T2, T2*, and T1rho have
been used to detect cartilage degeneration. However, these biomarkers are
sensitive to the magic angle effect. Magnetization transfer (MT) modeling provides
magic angle insensitive parameters such as macromolecular proton fraction (MMF).
This study focuses on the clinical evaluation of cartilage degeneration using 3D
ultrashort echo time cones MT (3D UTE-Cones-MT) modeling in osteoarthritis (OA)
patients. Both MMF and MT
ratio (MTR) show significant negative correlations with WORMS grading
of knee cartilage. This study highlights the
potential of 3D UTE-Cones-MT
techniques for detection of early cartilage degeneration in OA.
Introduction
OA of the knee joint is one of the most common forms of
arthritis. Various cartilage pathologies, such as the depletion of
proteoglycan (PG) or degeneration of the collagen network, are directly
associated with the onset and progression of knee OA [1].
Therefore, it is crucial for clinicians to detect structural and functional
changes of the cartilage in the early stages of OA using a non-invasive and
sensitive method. Many quantitative MRI techniques, such as T2, T2*, and T1rho
have been used to detect the early degeneration of cartilage, but these
parameters are sensitive to the magic angle effect, which may confound their
use in clinical practice [2-3]. Magnetization transfer (MT)
modeling provides biomarkers, such as macromolecular proton fraction (MMF) and
exchange rates, which are magic angle insensitive [2] and have
been shown to be associated with collagen degradation and PG depletion [4].
With recent innovations in MR technology, especially the 3D UTE-Cones
sequence, the total scan time has been greatly decreased with more reliable
biomarkers such as MMF and MT ratio (MTR) [5-6]. However, until
now, clinical evaluation of the 3D UTE-Cones-MT technique on OA patients
remains to be investigated. This study aimed to investigate
the feasibility of using a two-pool model of 3D UTE-Cones-MT data for in
vivo assessment of whole knee cartilage in healthy volunteers and OA patients,
and to explore the relationship between 3D UTE-Cones-MT biomarkers and the
clinical score of OA patients.Methods
A
total of 62 human subjects (aged 23-88 years; 55±17 years; 32 males, 30
females) was recruited for this study. Informed consent was obtained from all
subjects in accordance with the guidelines of the Institutional Review Board. The
whole knee joint (26 left knees, 36 right knees) was scanned using 3D UTE-Cones
sequences on a 3T MR750 scanner (GE Healthcare Technologies, Milwaukee, WI). A
series of 3D UTE-Cones-MT sequences (saturation pulse power = 500°, 1000°,
1500°; frequency offset = 2, 5, 10, 20, 50 kHz; flip angle = 7˚) was used to
measure the MTR and the MMF. According to clinical exams and Kellgren–Lawrence
(KL) scores [7], all subjects were classified into three groups: 18
normal controls (KL = 0), 27 patients with mild osteoarthritis (OA) (KL≤2), and
17 patients with severe OA (KL≥3); then, the whole knee articular cartilage was
scored by two experienced musculoskeletal radiologists according to the
Whole-Organ Magnetic Resonance Imaging Score (WORMS) [8] using the
fat-suppressed T2-weighted FSE images. Furthermore, according to the extent and
the depth of the cartilage lesions, all subjects were further subdivided into
two groups: the extent groups (WORMS 0 = controls, WORMS 1, 2, 2.5 = regional
lesions, WORMS 3, 4, 5 = diffuse lesions) and the depth groups (WORMS 0 =
controls, WORMS 1, 2, 3, 4 = partial thickness lesions, WORMS 2.5, 5 = full-thickness
lesions). The correlations between MT parameters and WORMS were calculated,
and the difference of MT parameters among different KL scores and WORMS groups
was evaluated and compared.Results and Discussion
The
Spearman’s rho correlation coefficient showed a moderate negative relationship
between the MMF/MTR and the corresponding WORMS. MMF decreased from 11.85±1.93%
to 10.69±2.10%, while MTR decreased from 42.28±6.01% to 40.05±5.79%, with the
increase of KL scores from 0 to 3. There is a similar trend in MMF and MTR with
the increase of WORMS (Table 1). The differences in MMF and MTR among different
KL groups (i.e. controls vs. mild OA, controls vs. severe OA, and mild OA vs.
severe OA) were all statistically significant (P<0.05). The differences for
MMF and MTR among different WORMS groups (i.e. controls vs. regional lesions,
controls vs. diffuse lesions, regional lesions vs. diffuse lesions; and
controls vs. partial thickness lesions, controls vs. full-thickness lesions,
partial thickness lesions vs. full-thickness lesions) were all statistically
significant (P<0.05). Regional analyses show stronger correlations between 3D
UTE-Cones-MT biomarkers and WORMS in patella and femoral condyles, but lower
correlations in tibial plateau (Table 2). Conclusion
Both
MMF and MTR obtained from the two-pool modeling of 3D UTE-Cones-MT data show
negative correlations with WORMS grading of knee cartilage. There is a statistically
significant difference among the different KL score groups and the different WORMS
groups. Stronger correlations between 3D UTE-Cones-MT biomarkers and WORMS were
observed in patella and femoral condyles, with lower correlations in tibial plateau.
This study highlights the potential of 3D UTE-Cones-MT techniques for detection of early cartilage degeneration
in OA.Acknowledgements
The authors acknowledge grant support from NIH(R01AR075825, 2R01AR062581, 1R01AR068987), and the VA Clinical Science and Rehabilitation R&DAwards(101RX002604).References
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