Synopsis
R1ρ, R2,
and R2* imaging have been considered as biomarkers of degenerative
cartilage diseases. In order to ensure
the reliability of these measurements, we acquired data in eight subjects twice
and compared measurements of variability.
R1ρ-measurements had lower variability (CVRMS=21%)
and a higher correlation to age (r2-value=0.566) when compared to R2
(r2-value=0.183; CVRMS=25%) and R2* (r2-value=0.092;
CVRMS=38%). These
measurements suggest that R1ρ is a more sensitive biomarker than R2
or R2*.INTRODUCTION
Osteoarthritis (OA) of the knee affects over 14% of those
aged over 45 years old in Europe and the US1. Although there are methods to image late stage disease, there is no clinical imaging method for early
detection of OA2. OA has been
linked to damage and loss of proteoglycans and collagen in articular cartilage3. These macromolecular changes due to OA may be
detectable through quantitative R2, R2* and R1ρ
MRI4,5,6.
Accurate relaxivity quantitation can be difficult due to B0
and B1 inhomogeneity effects during R2, R2*, and R1ρ quantitation7,8,9, as well as due to diurnal
changes10. Measurements of
variability can help demonstrate the repeatability and overall effectiveness of
relaxivity measurements11. Cartilaginous
knee relaxivity studies often use multiple regional ROIs11, which
could confound measurements and introduce observer bias. These studies also have not shown comparisons
to R2* that could be sensitive to the negative charge of
proteoglycans. To compare the effectiveness
of each technique, we show these relaxivity measurements at 3T using a single
large ROI in the cartilage.
METHODS
Eight healthy volunteers ranging
from 24 to 48 years old were scanned twice, between one week and four months
apart (average = 80 days). All studies had ethical approval. Quantitative R2 and R1ρ
3D fast-spin echo12 (FSE)
sagittal images were acquired with:
matrix = 320x256x48, FOV=160x160x144 mm3, ETL = 45, T1
recovery time = 900 ms, NEX = 0.5, bandwidth = ±62.5 kHz, scan time = ~5
minutes with TEs = 7, 13, 27, and 41 ms for R2 imaging or spin-lock
B1 of 500 Hz and TSLs = 1, 10, 30, and 50 ms for R1ρ imaging.
Quantitative R2* 3D multi-echo gradient echo imaging13
(GRE) images were acquired with: matrix = 384x268x84, FOV=160x112 x144 mm3,
scan time = ~3.5 minutes, TEs=7, 13, 19, 25, 31, and 37 ms. Two subjects did not have complete data sets.
A large region of femoral cartilage was manually segmented, and the
relaxivity means, percent difference of the two means for each subject, and
coefficient of variations (CV = σROI/μROI) were collected for each ROI11. The mean percent difference (=100% x Σ(μ1-μ2)/ μ1n, where μ1 is the larger mean percent difference), and CVRMS9
(=(√ΣCV/n)
are reported. A linear r2-correlation
was performed for relaxivity versus age, as cartilaginous degradation is
expected with age.
RESULTS
Figure 1 shows images and relaxivity results from
a single volunteer.
Figure 2 shows the mean relaxivity measurements for each volunteer vs.
age. The mean for R
1ρ, R
2, and R
2*
respectively were 22, 28, 23 Hz; the mean percent difference was 4.6%,
9.6%, and 8.0%; CV
RMS was 21%, 25%, and 38%; and, the r
2-correlations
were 0.566, 0.092, and 0.183.
DISCUSSION
We obtained similar mean values of R1ρ and R2
as previously published studies9,11. Our mean R1ρ (22 Hz) of healthy volunteers was higher than the mean R1ρ associated with early OA from published studies (16 Hz)14, while our mean R2 was similar to the mean associated with early OA14 (28±1 Hz). The mean percent difference between the two scan sessions (4.6%) remained lower than published differences in R1ρ in healthy and OA subjects14 (14%).
R1ρ variability measurements (both percent difference and CVRMS) were lower than those
of R2 and R2*, despite using similar ROIs, suggesting R1ρ
has better repeatability. We obtained higher CVRMS (=22%) than published studies
(=7-14%), although this may be due to a single large ROI instead of multiple
regional ROIs, or possibly due to a difference in the CVRMS
calculation method.
R1ρ showed a r2-correlation
versus age (r2-value=0.566, p<0.01), while the other parameters showed low correlations (R2
r2-value= 0.183, p=0.11; R2* r2-value=0.092, p=0.29). Articular proteoglycan degradation with age, due to articular matrix alterations at weight-bearing locations, is well-confirmed15. These r2-correlation results suggest that R1ρ imaging is more sensitive to these age-related changes than R2 or R2*.
CONCLUSION
R
1ρ
showed lower variability than R
2
and R
2*,
suggesting that it is a repeatable biomarker. R
1ρ
measurements had a higher correlation with age, suggesting it may be a more
sensitive biomarker than R
2 or R
2*.
Acknowledgements
This work was supported
by GE Healthcare, GlaxoSmithKline, and EPSRC Grant RQAG/067.References
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