Vladimir Juras1,2, Markus Schreiner1, Rahel Heule3, Pavol Szomolanyi1,2, Stefan Zbyn1,4, Vladimir Mlynarik1, Stefan Marlovits5, Didier Laurent6, Celeste Scotti6, Joerg Goldhahn6, Kubiak Ewa6, Haber Harry6, Ivan Frollo2, Oliver Bieri3, and Siegfried Trattnig1,7
1Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria, 2Department of Imaging Methods, Slovak Academy of Sciences, Institute of Measurement Scinece, Bratislava 4, Slovakia, 3Division of Radiological Physics, University of Basel Hospital, Basel, Switzerland, 4Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland, 5University Clinic for Trauma Surgery, Medical University of Vienna, Vienna, Austria, 6Novartis Institutes for Biomedical Research, Basel, 7CD Laboratory for Clinical Molecular MR Imaging
Synopsis
Transverse
relaxation time (T2) maps were assessed
as a potential marker for the long-term follow-up of the patients with
cartilage lesions ICRS Grade I-II in four time points (baseline, 8 days, 3 and
6 months). T2 mapping was based on
a 3D triple echo steady state imaging sequence delivering high quality
high-resolved T2 maps at ultra-high
field MRI. The results showed opposite trends of T2
values at 3T (a decrease) and 7T (an increase) over time. The statistically
significant difference was found in case of deep zone of the cartilage lesion
at 3T. T2 mapping could be used in
the future as a good alternative to cartilage biopsies in clinical trials on
new therapies aimed at cartilage regeneration.
Introduction:
Cartilage
degeneration is a major source of pain and disability in Western societies and
there is a strong demand for a noninvasive tool that allows for early diagnosis
and monitoring. Biochemical changes of the extracellular matrix often precede
the morphological changes(1). Quantitative MRI has shown a great potential to
non-invasively detect such changes, especially T2 mapping which is
expected to be sensitive to collagen matrix anisotropy/organization and water
content. Changes in articular cartilage during OA or in acute lesions result in
an increased hydrodynamic fluid pressure and increased stress throughout the
matrix. This leads to the proteoglycan-collagen matrix degeneration and
cartilage tissue loss(2). In this study, we investigated T2 maps as
a possible marker for following-up the patients after cartilage injury. Methods
Eleven patients (mean age, 48.4/9.6
years; 5 males/6 females) were imaged. All of them had confirmed femoral cartilage
defect(s) in the knee joint (ICRS Grade I or II). Cartilage T2 maps were acquired for each of these
patients on two MR scanners: 3T Trio (Siemens, Erlangen, Germany) and 7T whole-body
investigational MR scanner (Siemens Healthcare, Germany). The
measurements were repeated four times (baseline (B), 8 days (8D), 3 months (3M)
and 6 months (6M)). T2 relaxation
times were determined using a 3D-Triple Echo Steady State sequence (3D-TESS)(3) with the following parameters: TR/TE 11.14/5.06 ms; FA 15°; TA 3:48 min, voxel
size 0.25x0.25x3 mm. For image analysis, regions of interest (ROIs) were
defined in 3D-double echo steady-state (DESS) morphological images in the region
suspicious for a cartilage defect and in a region of normal-appearing cartilage
(weight bearing and non-weight bearing region) in both deep and superficial
cartilage layers. ROIs were transferred onto T2
maps. Student’s t-test was used to determine the differences in T2 in various time points at different
field strength. A P-value<0.05 was considered statistically significant.Results
Illustrative
T2 maps with the ROI position are shown on Fig. 1. The following
statistical significances were found (mean at 3T (value (standard deviation))
are in ms) lesion superficial (B → 41.8
(10.29) vs 3M → 35.5 (18.13), p=.0408) and lesion deep (B →32.6 (11.73) vs 6M → 26.6 (6.49), p=.0084). At 7T, the following statistical
significances were found: weight bearing superficial (B → 31.9 (9.79) vs 3M → 30.4
(6.56), p=.0155), non-weight bearing superficial (B → 24.8 (5.74) vs 3M → 22.3
(7.12), p=.0258) and weight bearing deep (B → 32.2 (9.48) vs 3M → 28.9 (1.92),
p=.0360). Unlike at 3T, the T2 values of the lesion at 7T increased over
time; however, without statistical significance: lesion superficial (B → 29.9 (8.13) vs 6M →32.7 (12.06)) and lesion deep (B → 24.5 (7.15) vs 6M 29.6 (11.74)). All values are listed in
the Table 1.Discussion
The results of this
study showed that the collagen network disorganization and/or water content can
be detected in patients with low-grade lesions and followed-up over time. Morphologically,
no change in lesion grade was found for all but one patients (worsening to
Grade II/III) in the time course. Interestingly, the trends of the T2 change in time were not the same at 3T
and 7T. A possible explanation of this result
could be that 3D-TESS is sensitive to the short T2
relaxation component which is present at 3T, but it is it decayed very fast at
7T due to chemical exchange contribution and diffusion in non-homogeneous
magnetic field. The short component is more likely linked to water with its
motion restricted by collagen network, and the long component is rather
reflecting bulk water. Although 3D-TESS T2
mapping is B1 insensitive by its nature, in some cases of extreme B1
(and/or B0) imperfections, the signal drops so much that the
reconstruction did not iterate to reasonable T2
values. However, these cases were rather rare and did not affect the overall
evaluation.Conclusion
T2 mapping with 3D-TESS enables monitoring of
changes in low-grade cartilage lesions and follow-up of patients over time also
at ultra-high field MRI. T2
might be a valuable marker for monitoring cartilage development after
regenerative therapy, as it may allow differentiation between the early
formation of hyaline and fibrotic cartilage without resorting to serial
biopsies.Acknowledgements
This work was supported by the Slovak Research and Development Agency:
APVV-15-0029, Grant Agency of the Slovak Academy of Sciences (VEGA 2/0001/17) and Austrian Science Fund (FWF) KLI541-B30.References
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