A New High-resolution 3D gagCEST Imaging method for In Vivo Human Knee Cartilage at 7T
Guruprasad Krishnamoorthy1, Ravi Prakash Reddy Nanga1, Puneet Bagga1, Hari Hariharan1, and Ravinder Reddy1

1Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States


Osteoarthritis (OA), one of the most prevalent musculoskeletal conditions, affects a large number of people around the world with an increased risk on an even larger number of people getting affected by it in the future [1]. GAG chemical exchange saturation transfer (gagCEST) is a promising MRI technique to non-invasively quantify GAG content present in the cartilages [2]. In this study, a new burst mode magnetization preparation 3D gagCEST technique was developed which provided high-resolution gagCEST maps of knee cartilages in practically achievable scan times at 7T with more than twice the sensitivity of the previously reported steady-state saturation 3D gagCEST study [5].


To design and develop a new high sensitivity 3D gagCEST technique to quantify glycosaminoglycan present in human knee cartilage in a practically achievable scan time.

Materials & Methods

All the human scans were performed under an approved Institutional Review Board protocol of the University of Pennsylvania. MRI scans were performed on 2 healthy male subjects in the age range 20 – 35 years and one symptomatic male subject aged 65 years old, with knee pain at Siemens 7T whole body MRI scanner (Siemens Medical Solutions, Malvern, PA) using a 28-channel receive array knee coil (Quality Electrodynamics, Mayfield Village, OH). A new 3D ‘burst mode’ sequence was developed as shown in Fig 1. In the burst mode magnetization prepared 3D sequence, the repetition time between magnetization preparation pulses is set to be long (> 3 x T1). This ensures that the bulk water signal has fully recovered from the previous preparation pulse. Now, to optimize scan time, we used very long low flip angle segmented gradient echo (GRE) readout with elliptically centered ordering for slice encoding (kz) and phase encoding (ky). For CEST, a frequency-selective saturation pulse train of 5 Hanning windowed pulses with the duration of 99.8 ms, with a 0.2 ms gap, with a B1rms of 2.2 µT was used [1]. For B0 mapping with Water Saturation Shift Referencing (WASSR) [2], a frequency-selective saturation pulse train of 2 Hanning windowed saturation pulses with a B1rms of 0.3 µT was used. For B1 map generation, hard pulses with two predefined flip angles are used for magnetization preparation. A new concentration independent B1 calibration method was developed. Spatial encoding parameters were slice thickness = 3 mm, number of slices = 16, flip angle = 5°, TR/TE = 7.8/3.6 ms, FOV = 140 mm with 0.6 mm2 in-plane resolution for both axial and coronal orientations. The total scan time for acquisition in both the axial and coronal orientations was 50 min, which includes positioning of the knee as well as the shimming for B0 inhomogeneity.


In all the datasets acquired, with both axial and coronal orientations, SNR of cartilages in the images with no saturation magnetization was ~95. For the ROI’s chosen from the healthy regions, CEST asymmetry at 1 ppm from steady-state method [3] is ~3% while that for the burst saturation method is ~7%. Representative slice of gagCEST maps with M0 (water magnetization image with no preparation pulse) and Mz- (water magnetization image with preparation pulse corresponding to -1 p.p.m.) normalizations of patellar and femoral-tibial cartilages from a young healthy volunteer and an elderly subject with reported knee pain are shown in Figs. 2A and 2B. The elderly subject’s patellar cartilage was found significantly thinner than the young subject’s cartilage while this thinning was not observed in the femoral and tibial cartilages. The mean CEST contrast values from the entire cartilage region for both normalizations are shown in Figs. 2C and 2D. Mz- normalization showed a better dynamic range (~9% to ~16%) than the M0 normalization (3.7% to 4.3%). Also, Mz- normalization showed better discrimination between the patellar cartilage of the healthy young subject and the elderly subject (mean gagCEST values, 12.75 ± 4.7% and 9.48 ± 3.7%). The final gagCEST images calculated after motion correction, B0 and B1 correction and Mz- normalization are shown in Fig. 3. One can clearly see layer-wise differences in gagCEST maps.


The new burst mode magnetization preparation 3D gagCEST method along with separate B0 and B1 inhomogeneity estimation and correction, yielded reliable and reproducible high-quality gagCEST maps with clear visualization of knee cartilage layers. The longer repetition times between saturation pulses and elliptical-centric ordered segmented gradient echo (GRE) readout seems to maintain high sensitivity, while in the steady-state method the CEST sensitivity was lower due to the use of very short repetition times between saturation pulses and the addition of a water saturation pulse to maintain constant initial magnetization.


This project was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health through Grant Number P41-EB015893 and the National Institute of Neurological Disorders and Stroke through Award Number R01NS087516.


[1] Lawrence, R.C., et al., Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis & Rheumatism, 2008. 58(1): p. 26-35.

[2] Ling, W., et al., Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proceedings of the National Academy of Sciences, 2008. 105(7): p. 2266-2270.

[3] Singh, A., et al., Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magnetic Resonance in Medicine, 2012. 68(2): p. 588-594.

[4] Kim, M., et al., Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magnetic Resonance in Medicine, 2009. 61(6): p. 1441-1450.

[5] Benjamin Schmitt , D.B., Cartilage Quality Assessment by Using Glycosaminoglycan Chemical Exchange Saturation Transfer and 23Na MR Imaging at 7 T. Radiology, 2011. 260(1): p. 257-264.


Fig. 1. A. Block diagram of the 3D gagCEST sequence showing magnetization preparation block, acquisition block and T1 recovery block. B. Schematic diagram displaying elliptically centered ordering for combined phase encoding and slice encoding. The actual encoding order is determined by ordering the points in Ky - Kz space based on scaled Euclidean distance from the center.

Fig. 2. Effect of Normalization Strategy: A & B Final CEST maps of patellar and femoral-tibial cartilages from a young healthy subject as well as an elderly subject with knee pain normalized with M0 and MZ-. C & D Bar plots represent gagCEST asymmetry from cartilages

Fig. 3. A. Representative axial slices showing Mz- normalized gagCEST maps of a healthy subject’s Patellar cartilage showing layer-wise differences in the gagCEST values B. Representative coronal slices showing gagCEST maps of Femoral and Tibial cartilage. Weight bearing regions exhibit relatively higher gagCEST values than the non-weight bearing regions. Note that the maps are overlaid on the corresponding anatomical images and cropped to show cartilages alone.

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