Comparison of gagCEST and sodium MRI in evaluating knee cartilage in vivo at 7 Tesla
Vladimir Mlynarik1,2, Stefan Zbyn1, Markus Schreiner3, Vladimir Juras1, Pavol Szomolanyi1, Didier Laurent4, and Siegfried Trattnig1,2

1Department of Biomedical Imaging and Image-Guided Therapy, High Field MR Center, Medical University of Vienna, Vienna, Austria, 2CD Laboratory for Clinical Molecular MR Imaging, Vienna, Austria, 3Department of Orthopedic Surgery, Medical University of Vienna, Vienna, Austria, 4Novartis Institutes for Biomedical Research, Basel, Switzerland

Synopsis

There are several methodological and data processing issues in gagCEST, which complicate the translation of this method into clinical practice. For assessing performance of the gagCEST protocol optimized in our laboratory, corrected signal intensities from sodium images were used as a reference. The results demonstrate a good correlation between both methods, although the small magnitude of the gagCEST effect and the low resolution in sodium images require carefully optimized methodology and long measurement times. It can be concluded that the gagCEST method can be useful in evaluating early degeneration of articular cartilage at 7 Tesla.

Target audience

MR physicists and radiologists interested in the evaluation of biochemical status of articular cartilage

Introduction

A decrease in concentration of glycosaminoglycans (GAG) in articular cartilage is associated with early manifestation of osteoarthritis. However, quantification of GAGs in articular cartilage in vivo is difficult. Several methods have been suggested to be sensitive to the changes in GAG concentration, namely dGEMRIC, T1ρ mapping, sodium imaging and recently gagCEST. The gagCEST method is promising since it is noninvasive, it does not need extra hardware and the relation of gagCEST values to the GAG concentration have been demonstrated in vitro on naturally degenerated cartilage specimens (1). Similarly, sodium MRI has been validated for the evaluation of GAG concentration in cartilage (2). In our study, we attempted to validate the performance of the optimized gagCEST method for the GAG content evaluation in vivo at 7 Tesla by using corrected sodium signal intensities (cSI) as a reference.

Subjects & Methods

Five patients with acute cartilage injury were measured twice with an interval of 8 days between the examinations. The gagCEST and sodium MRI experiments were done on a 7T MR System (Siemens, Erlangen, Germany) using a 28-channel knee array coil and a 15-channel sodium-only array coil (both Quality Electrodynamics LLC, Cleveland, OH), respectively. For gagCEST, a segmented 3D RF-spoiled gradient-echo (GRE) sequence (TE=3.15ms, TR=7.9ms, resolution=0.9×0.9×2.2mm3) was used in combination with presaturation before each segment by means of ten 60-ms adiabatic full passage hs2 RF pulses followed by spoiling gradients. The nominal frequency of the pulses in the train was varied in a range of ± 20 Hz. Nineteen scans with equidistant (93 Hz) offsets in the range of 1680 Hz around the water resonance and a scan without saturation were collected, resulting in a scan time of 20 min. The amplitude of the saturation pulses corresponded to about 80% of the SAR limit. Z-spectra were extracted from registered images and their asymmetry (MTRasym) was calculated from integrals over the offset range ±∂ = 0.6–1.8 ppm relative to the minimum of each individual Z-spectrum. Sodium images were measured using a 3D vTE-GRE sequence with variable echo times, TR=9.2 ms, TEmin/TEmax =1.22/1.82 ms, FA=51º, bandwidth=100 Hz/pixel, resolution=1.6×1.6×3.0 mm3 and a scan time of 25 min.

Results

In the sagittal sodium images and gagCEST maps (Fig. 1), regions of interest were selected in weight-bearing and non-weight-bearing zones of femoral condyles, in patellar and tibial cartilage. For the correlation between cSI and MTRasym values, mean values of two measurements in the selected regions were used. A good agreement between results of these two methods was observed (Fig. 2). Without considering an outlier, the correlation coefficient was about 0.9. It was also observed that cartilage properties may not be strictly bound to its weight-bearing or non-weight-bearing function and may vary in a relatively broad range.

Discussion

Sodium signal intensities can be affected by hardware imperfections and by partial volume effect due to low spatial resolution of sodium images. In this study, the reported sodium signal intensities were corrected for inhomogeneous B1 field (3) and for the partial volume effects. On the other hand, the gagCEST values can be affected by the mode of saturation (including direct saturation of water), by the exchange rate and by relaxation times of water and exchangeable protons in the tissue (4). In spite of these limitations, a good agreement between the MTRasym and cSI values was observed. Because the relation between sodium signal intensities and the GAG concentrations is relatively straightforward and has been proven experimentally, it can be concluded that gagCEST can also be useful in estimating GAG concentration in knee cartilage in vivo. The outlying value in Fig. 2 indicates that corrections for unusual properties of cartilage might be necessary in some cases.

Acknowledgements

The study was supported by a grant provided by Vienna Science and Technology Fund, Project WWTF-LS11-018.

References

1. Brix M, Mlynarik V, Schmitt B, et al. Evaluation of the GAG content of articular cartilage in the knee joint using gagCEST: correlation to the gold-standard with multicompartmental biochemically analyzed GAG content. Proc Intl Soc Mag Reson Med 22, 3985 (2014).

2. Wheaton AJ, Borthakur A, Dodge GR, et al. Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis. Acad Radiol. 2004;11:21-8.

3. Zbýn Š, Brix MO, Juras V, et al. Sodium magnetic resonance imaging of ankle joint in cadaver specimens, volunteers, and patients after different cartilage repair techniques at 7 T: initial results. Invest Radiol. 2015; 50:246-54.

4. Zaiss M and Bachert P. Chemical exchange saturation transfer (CEST) and MR Z-spectroscopy in vivo: a review of theoretical approaches and methods. Phys Med Biol. 2013; 58:R221–R269.

Figures

Fig. 1. From left to right: Morphological T2-weighted 3D-DESS image of cartilage structures in the knee, a corresponding gagCEST map and a sodium MR image

Fig. 2. Correlation between MTRasym and sodium cSI values in regions of interest selected in various parts of knee cartilage



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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