CEST phase mapping using a length and offset varied saturation (LOVARS) scheme

Abstract

Chemical exchange saturation transfer (CEST) MRI is a promising new technique for cellular and molecular imaging. This contrast allows the detection of tumors and ischemia without the use of gadolinium as well as the design of microenvironment-sensitive probes that can be discriminated based on their exchange contrast properties and saturation frequency. Current acquisition schemes to detect and analyze this contrast suffer from sensitivity to spatial B0 inhomogeneity and low contrast-to-noise-ratio (CNR), which is an obstacle to widespread adoption of the technology. A new method to detect CEST contrast is proposed here, termed “Length and Offset VARied Saturation” or “LOVARS”, which acquires a set of images with the saturation parameters varied so as to modulate the exchange contrast. Either fast fourier transform or the general linear model can be employed to decompose the modulation patterns into separate sources of water signal loss. After transformation, a LOVARS phase map is generated, which is insensitive to B0 inhomogeneity. When collected on live mice bearing 9L gliosarcomas, and compared to the conventional MTRasym map using offset increment correction, the results show that LOVARS phase mapping obtains about four times higher CNR and exhibits less B0 artifacts.

Nuts and bolts of chemical exchange saturation transfer MRI

“…The arrows point to the average phase (bottom) and magnitude (middle) in ROI1 and ROI2 at 1cycle/LU based on FFT; e) LOVARS phase map calculated using FFT; f) LOVARS phase map calculated using GLM; g) thresholded LOVARS imaginary component map. Reproduced from reference (125) with permission. …”

“…In addition, this method lacks the capability of discerning CEST contrast from conventional MTC. Other alternatives include the LOVARS (125), and SAFARI (114) schemes which will be described in the Strategies to separate MT and CEST section.…”

“…Based on the amplification mechanism of CEST imaging that the contrast builds up as t sat increases, CEST contrast can also be detected and characterized using time-domain analysis based methods(73,125,135,136). For example, Song et al developed a new time-domain CEST mapping method, termed “Length and Offset VARied Saturation” or “LOVARS” (125) (Fig. 9) based on both the Length (t sat )-dependence and asymmetric (around water) Offset-dependence of CEST contrast.…”

Biomolecular MRI reporters: Evolution of new mechanisms

“…However, in in vivo applications, biomolecular CEST agents must also overcome background CEST contrast from endogenous proteins, making their detection at such low concentrations more difficult. Despite this limitation, protein-based CEST reporters have been used in several in vivo applications, and innovative pulse sequences and processing schemes have been developed to help maximize reporter-specific contrast [38–40]. …”

Cellular and Molecular Imaging Using Chemical Exchange Saturation Transfer

“…We have developed an approach, termed Length and Offset VARied Saturation (LOVARS) (109), in which the length ( t sat ) and Δω of the saturation pulse is varied to modulate the water signal loss and impart differential phases on the interfering components. This allows their separation from the desired probe signal using post-processing techniques similar to those used to analyze time-varying signal changes in event-related fMRI (110-116), such as Fast Fourier Transform (FFT) to separate different frequency components(109). Finally, it is key to repeatedly use the against with the highest standard of rigorous and reproducibility(117), in order to achieve highly sensitive, user-friendly imaging probe.…”