Peng Luo1, Wentao Hu2, Yongming Dai2, and Guanwu Li1
1Department of Radiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China, 2Central Research Institue, United Imaging Healthcare, Shanghai, China
Synopsis
Keywords: Cartilage, Diffusion/other diffusion imaging techniques
Early OA is
subclinical for anatomic change of cartilage, making it difficult for
conventional MRI detection. This study is aimed to apply diffusion-relaxation
correlation spectrum imaging (DR-CSI) to knee early-stage OA detection. DR-CSI
compartment volume fractions V
A, V
B and V
C had correlation with the modified
Whole-Organ MR Imaging Scores (WORMS). V
C had better
ability than V
A, V
B, V
D, T2 and ADC to discriminate early OA patients from
healthy controls. The results illustrated that DR-CSI compartment volume
fractions may be sensitive indicators for detecting early-stage degeneration in
knee articular cartilage.
Introduction
Articular
cartilage is a key tissue for the early diagnosis of osteoarthritis (OA). As
cartilage degenerates irreversibly, detecting and monitoring early OA has
significant clinical implication. However, early OA is subclinical for anatomic
change of cartilage, making it difficult for conventional MRI detection [1]. Cartilage
degeneration occurs firstly at a molecular level, associating tightly with
increased water content, depletion of proteoglycans, and disorganization of the
collagen networks [2].
Recently,
an interesting approach combining the idea of compositional and multiparametric
methods, named multi-dimensional correlation MRI, has been developed [3-4]. This
study is aimed to apply one of the 2D-correlated MRI, diffusion-relaxation
correlation spectrum imaging (DR-CSI), to knee early-stage OA detection.Methods
Forty
early osteoarthritis (OA, Kellgren-Lawrence [KL] score 1 to 2; mean age, 58.6
years) and twenty-three healthy volunteers (mean age, 59.4 years) underwent
DR-CSI scan by 3.0T MR (uMR780, United Imaging Healthcare, Shanghai, China). The
structural abnormalities of articular cartilage were evaluated by the modified
Whole-Organ MR Imaging Scores (WORMS).
The DR-CSI measurements include spin-echo
echo-planar diffusion-weighted images (SE-EP-DWI) with combinations of b-values
(01, 2001, 4001, 8001, 10002,
12003 s/mm2, with the subscript denoting the number of
averages) and echo times (TE = 90, 105, 120, 135 and 150 ms). DR-CSI assumes
the signal to be [3]
$$S(x,y,b,TE)\int\int
f(x,y,D,T2){e}^{-bD}{e}^{TE/T2}\text{d}D\text{d}T2$$
where f is the spectral intensity to be fitted. Regions of interest (ROI) were manually placed on the
high-resolution fat-suppressed proton-density-weighted images (PDWI) to cover
the knee cartilage, and then mapped to the DWI images for DR-CSI
post-processing. A spectrum segmentation was performed for quantitative
analysis. All the spectra were divided into four compartments, A (slow D, short
T2), B (fast D, short T2), C (fast D, long T2) and D (slow D, long T2),
indicating four tissue components or compartments. The thresholds dividing
these compartments (1.2
μm2/ms, 40 ms) were decided after
a survey over previous studies of cartilage [5-7]. Volume fraction Vi for DR-CSI compartment i
(A, B, C, D), and conventional ADC and T2 were obtained.
Vi were compared
between Early OA and control group the Mann–Whitney U test or Student’s t-test where
appropriate. Spearman’s
correlation was used to assess the relationship between WORMS and DR-CSI Vi.
Sensitivity, specificity, and positive and negative likelihood ratio (PLR, NLR)
of Vi were assessed to determine the diagnostic accuracy for
detection of early-stage degeneration.Results
The
representative volume fraction Vi for DR-CSI compartment i (A,
B, C, D) maps at the knee joint (lateral cartilage)
from a control subject and early OA are shown in Figure 1. Comparisons among the
DR-CSI compartment volume fraction (VA, VB, VC, and VD)
of the healthy controls and early OA patients are summarized in Figure 5. Early OA
versus the controls had significantly higher VC (36.5% vs 23.1%),
lower VA (10.2% vs 14.2%) and VB
(45.6%
vs 51.8%), but comparable VD (p>0.05). VA
(rho=-0.463),
VB (rho=-0.445)
and VC (rho=0.572) had a moderate association
with WORMS. No significant correlation was identified between VD and
WORMS. VC had better ability than VA,
VB, VD, T2 and ADC to discriminate early OA patients from
healthy controls (area under the curve, 0.87). Sensitivity, specificity,
PLR, and NLR of VC with cutoff value 28.9% were 80.0% (95% CI, 64.4%
- 90.9%), 91.3% (72.0% - 98.9%), 9.20% (7.5% - 11.2%), and 0.22% (0.05% -
0.9%).Discussion
Our results
showed that DR-CSI VC has a clear positive correlation with WORMS of articular
cartilage, and could be a better marker for the diagnosis of early OA than
conventional ADC and T2 value. The conclusion that cartilage tissue of OA holds
more components with high diffusivity and high T2, to some extent, was in
agreement with some previous reports using T2 mapping or DWI sequence alone [5,8-9].
The cartilage tissue ultrastructure deterioration leads to increased hydration
and loss of collagen and proteoglycans, enhancing the water permeability and
average diffusion rate of cartilage, and finally results in lift of signal
contribution from high diffusivity and long T2 compartment [10].
Spatial
distribution of different compartments could be obtained, displayed by Vi
maps, as a tool for diagnosis. Although these V maps have inherent association
with ADC and T2 maps, extra information can be found. Emphasis could be put on
areas with large C contribution, where cartilage degeneration might have begun.Limitations
First,
due to lack of absence of arthroscopy for the histopathological reference
standard, accurate association between OA and histology is not achieved.
Second, the shortest TE is 90 ms long, causing the decay of some cartilage
signal.Conclusions
DR-CSI
compartment volume fractions may be sensitive indicators for detecting early-stage
degeneration in knee articular cartilage.Acknowledgements
We thank the participants and Ruiping
Wang, PhD., Drs. Wei Fang, Ze Yuan and Weiqin Lu, for their invaluable
assistance with statistical analysis, participant selection, and technical
support.References
1.
Roemer FW, Guermazi A, Demehri S, Wirth W, Kijowski
R. Imaging in Osteoarthritis. Osteoarthritis Cartilage. 2022;30(7):913-34.
2.
Hunter DJ, Bierma-Zeinstra S.
Osteoarthritis. The Lancet.
2019;393(10182):1745-59.
3.
Kim D, Doyle EK, Wisnowski JL,
Kim JH, Haldar JP. Diffusion-relaxation correlation spectroscopic imaging: A
multidimensional approach for probing microstructure. Magn Reson Med. 2017;78(6):2236-49.
4.
Benjamini D, Iacono D, Komlosh
ME, Perl DP, Brody DL, Basser PJ. Diffuse axonal injury has a characteristic
multidimensional MRI signature in the human brain. Brain. 2021;144(3):800-16.
5.
Raya JG, Horng A, Dietrich O, et al. Articular
cartilage: in vivo diffusion-tensor imaging. Radiology. 2012;262(2):550-9
6.
Mlynarik V, Sulzbacher I, Bittsansky M, Fuiko R,
Trattnig S. Investigation of apparent diffusion constant as an indicator of
early degenerative disease in articular cartilage. J Magn Reson Imaging. 2003;17(4):440-4.
7.
Dunn TC, Lu Y, Jin H, Ries MD, Majumdar S. T2
relaxation time of cartilage at MR imaging: comparison with severity of knee
osteoarthritis. Radiology. 2004;232(2):592-8.
8.
Dunn TC, Lu Y, Jin H, Ries MD, Majumdar S. T2
relaxation time of cartilage at MR imaging: comparison with severity of knee
osteoarthritis. Radiology. 2004;232(2):592-8.
9.
Liebl H, Joseph G, Nevitt MC, et al. Early T2
changes predict onset of radiographic knee osteoarthritis: data from the
osteoarthritis initiative. Ann Rheum Dis. 2015;74(7):1353-9.
10.
Guermazi A, Alizai H, Crema MD, Trattnig S, Regatte
RR, Roemer FW. Compositional MRI techniques for evaluation of cartilage
degeneration in osteoarthritis. Osteoarthritis Cartilage. 2015;23(10):1639-53.