Chemical exchange saturation transfer MR imaging of articular cartilage glycosaminoglycans at 3 T: Accuracy of B₀ Field Inhomogeneity corrections with gradient echo method

Abstract

Glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) is an important molecular MRI methodology developed to assess changes in cartilage GAG concentrations. The correction for B₀ field inhomogeneity is technically crucial in gagCEST imaging. This study evaluates the accuracy of the B₀ estimation determined by the dual gradient echo method and the effect on gagCEST measurements. The results were compared with those from the commonly used z-spectrum method. Eleven knee patients and three healthy volunteers were scanned. Dual gradient echo B₀ maps with different ∆TE values (1, 2, 4, 8, and 10 ms) were acquired. The asymmetry of the magnetization transfer ratio at 1 ppm offset referred to the bulk water frequency, MTR_asym(1 ppm), was used to quantify cartilage GAG levels. The B₀ shifts for all knee patients using the z-spectrum and dual gradient echo methods are strongly correlated for all ∆TE values used (r = 0.997 to 0.786, corresponding to ∆TE = 10 to 1 ms). The corrected MTR_asym(1 ppm) values using the z-spectrum method (1.34% ± 0.74%) highly agree only with those using the dual gradient echo methods with ∆TE = 10 ms (1.72% ± 0.80%; r = 0.924) and 8 ms (1.50% ± 0.82%; r = 0.712). The dual gradient echo method with longer ∆TE values (more than 8 ms) has an excellent correlation with the z-spectrum method for gagCEST imaging at 3 T.

Introduction

Osteoarthritis (OA) is one of the leading causes of chronic disability and characterized by the gradual breakdown and eventual loss of joint cartilage [1], [2], [3]. This disease is a significant public health problem. Using prevalence estimates, the National Arthritis Data Workgroup reported that OA affects nearly 27 million Americans or 12.1% of the adult population in 2005 [4], [5]. While there are no recent estimates of medical costs for OA, 2003 US medical expenditures attributable to arthritis and other rheumatic conditions aggregated $81 billion, of which OA is likely to account for a large proportion [6].

X-ray can visualize OA changes of the bone, but it has limited ability to assess soft-tissue involvement. CT is better at providing assessment of soft-tissue and osseous changes, but is not very sensitive for evaluating the extent and severity of OA [7]. Magnetic resonance imaging (MRI) has been advancing over the past two decades with the development of cartilage-specific sequences and is unique for assessing meniscal and ligamentous disease related to OA, providing clinicians with more information regarding the health and status of the cartilage in situ [8], [9], [10], [11]. In addition to the commonly used morphological sequences, such as proton density-, T₁- and T₂-weighted, multiple advanced MRI imaging methods, including T_1ρ [12], [13] and ²³Na MRI [14], [15], have been developed to quantify regional variations in cartilage within its micro-architecture. Chemical exchange saturation transfer (CEST) MRI has been developed as a molecular MRI methodology which detects endogenous macromolecules indirectly through chemical exchange and cross-relaxation with bulk water protons [16], [17], [18], [19], [20], [21]. The extent of contrast depends on the concentration of available macromolecules. gagCEST-MRI appears to be capable of assessing glycosaminoglycans (GAGs) to detect early articular cartilage degeneration and glycosaminoglycan concentration changes in the intervertebral disc [22], [23], [24], [25], [26]. OA was reported to be associated with a decrease in GAG concentration before the observable joint space thinning or morphological changes in the cartilage matrix (Outerbridge grade II or more) [27], [28]. Thus, gagCEST-MRI can be performed as a useful tool to identify the concentration change of the biochemical components in vivo and provide complementary information to the routine MR imaging contrasts.

The gagCEST-MRI technique is based on the asymmetry in the z-spectrum between the 1 ppm offset (referenced to the bulk water frequency) where GAG hydroxyl protons resonate and the reference site at − 1 ppm. Although the magnetic field inhomogeneity is a common problem for CEST imaging [29], [30], the 1 ppm site where the gagCEST effect appears is much closer to the water resonance (0 ppm) than other targeted frequencies, such as 3.5 ppm where the amide proton transfer (APT) is assessed [31], [32], [33], [34], [35], [36], [37]. The small chemical shift difference makes it harder to distinguish the CEST effect from direct water saturation. The frequency shift even as small as 0.1 ppm in the z-spectrum is able to cause a dramatic change in the quantification of the GAG concentration. A B₀ correction is always necessary in the image post-processing stage. The conventional approach for this is to acquire saturation images over a range of frequency offsets with a fine frequency interval [29], [30]. Then, the whole z-spectrum is assessed by the high order polynomial fit and the B₀ map is obtained by looking for the lowest signal intensity in the spectrum (z-spectrum method). However, this scan requires a fairly long scan time (2–3 min) for a single slice due to the necessary sweep of the RF saturation frequency offsets. On the other hand, it is well known that a B₀ map can be acquired with the gradient echo method [38]. This scan requires much shorter time (usually less than 40 s) and is easy to be implemented on clinical scanners. The gradient echo method has been used in CEST imaging by several researchers [39], [40], [41]. Zhao et al. have compared the gradient echo field-mapping method and the z-spectrum based water saturation shift referencing method in APT imaging of human brain tumor at 3 T, showing the comparable MTR asymmetry results [40]. Dula et al. evaluated the high order polynomial fit and gradient echo B₀ mapping approaches in CEST imaging of brain at 7 T [41]. However, no previous study has been performed to quantitatively evaluate the performance of the gradient echo B₀ mapping methods with different echo times (TEs) and their effects on the gagCEST imaging. The purpose of this study is to examine and improve B₀ field inhomogeneity corrections in knee gagCEST imaging using the dual gradient echo B₀ mapping method. The widely used z-spectrum method was used as a standard reference in the study.