Nuclear magnetic relaxation dispersion of murine tissue for development of T₁ (R₁) dispersion contrast imaging

Abstract

This study quantified the spin-lattice relaxation rate (R 1 ) dispersion of murine tissues from 0.24 mT to 3 T. A combination of ex vivo and in vivo spin-lattice relaxation rate measurements were acquired for murine tissue. Selected brain, liver, kidney, muscle, and fat tissues were excised and R 1 dispersion profiles were acquired from 0.24 mT to 1.0 T at 37°C, using a fast field-cycling MR (FFC-MR) relaxometer. In vivo R 1 dispersion profiles of mice were acquired from 1.26 T to 1.74 T at 37°C, using FFC-MRI on a 1.5 T scanner outfitted with a field-cycling insert electromagnet to dynamically control B 0 prior to imaging. Images at five field strengths (1.26, 1.39, 1.5, 1.61, 1.74 T) were acquired using a field-cycling pulse sequence, where B 0 was modulated for varying relaxation durations prior to imaging. R 1 maps and R 1 dispersion (ΔR 1 /ΔB 0 ) were calculated at 1.5 T on a pixel-by-pixel basis. In addition, in vivo R 1 maps of mice were acquired at 3 T. At fields less than 1 T, a large R 1 magnetic field dependence was observed for tissues. ROI analysis of the tissues showed little relaxation dispersion for magnetic fields from 1.26 T to 3 T. Our tissue measurements show strong R 1 dispersion at field strengths less than 1 T and limited R 1 dispersion at field strengths greater than 1 T. These findings emphasize the inherent weak R 1 magnetic field dependence of healthy tissues at clinical field strengths. This characteristic of tissues can be exploited by a combination of FFC-MRI and T 1 contrast agents that exhibit strong relaxivity magnetic field dependences (inherent or by binding to a protein), thereby increasing the agents' specificity and sensitivity. This development can provide potential insights into protein-based biomarkers using FFC-MRI to assess early changes in tumour development, which are not easily measureable with conventional MRI. MRI has a history of constant technical progress towards higher magnetic field strengths for imaging. 1 The progressive increases in magnetic field strength have been spurred by significant gains in the signal-to-noise ratio (SNR), and spectral and spatial resolution exploited in imaging of anatomy and brain function. [2][3][4][5] While high and ultra-high magnetic field strengths are attractive for producing exquisite images of internal structures with unprecedented detail that aid in tissue characterization, imaging at these magnetic field strengths results in very little difference in the relaxation times of different tissues, thereby losing the variability of an important intrinsic tissue property that leads to image contrast. 6,7 Differences in Abbreviations used: B P , polarization magnetic field; B R , relaxation magnetic field; dreMR, delta relaxation enhanced MR; FFC-MR, fast field-cycling MR; FFC-MRI, fast field-cycling MRI; FID, free induction decay; FSE, fast spin-echo; NMRD, nuclear magnetic relaxation dispersion; NP, non-polarized; PP, pre-polarized; ROI, region of interest; SNR, signal-to-noise ratio

High‐Field Detection of Biomarkers with Fast Field‐Cycling MRI: The Example of Zinc Sensing

“…[21] In our example, if any free (not protein-bound) GdL or GdL-Zn is present, it will be "silent" (see Figure 3c), as the NMRD curves of such small complexes show no dispersion at these fields. For contrasta gents exhibitingalarge DR 1 /DB 0 ,t his small tissue R 1 dispersion (e.g., À0.19 s À1 T À1 for murine musclet issue at 1.5 T) represents an egligible anatomical background signal.…”

“…For contrasta gents exhibitingalarge DR 1 /DB 0 ,t his small tissue R 1 dispersion (e.g., À0.19 s À1 T À1 for murine musclet issue at 1.5 T) represents an egligible anatomical background signal. [21] In our example, if any free (not protein-bound) GdL or GdL-Zn is present, it will be "silent" (see Figure 3c), as the NMRD curves of such small complexes show no dispersion at these fields. On the other hand, the binding of GdL to HSA in the absence of Zn 2 + entails ad ispersion (background signal) that cannotb es uppressedi nt he FFC-MR image.…”

R 1 dispersion contrast at high field with fast field-cycling MRI

“…This leads to an improved target specificity by exploiting image contrast based on the increased dR1/dB0 of the bound CA instead of the absolute difference of the relaxation rate at a fixed magnetic field. Therefore, the dreMR image shows only contrast arising from the bound CA and supresses contrast from the anatomical background as well as from the unbound agent, which has been recently shown by in-vivo experiments with mice [6]. Hoelscher et al [4] extended the dreMR theory to quantitative concentration measurements using a correction for finite ramp times during field-cycling and a compensation of field-cycling induced eddy current fields by dynamic reference phase modulation [7].…”

Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives

“…Magnetisation-prepared spin-echo pulse sequences have been commonly used in FFC-MRI to determine R 1 dispersion maps (e.g. in [15,30,31]); this has been adopted as it corresponds to the gold-standard way to measure R 1 . In the most general case, it comprises three phases between which the magnetic field B 0 is switched: polarisation, evolution and acquisition [11].…”

“…In contrast to conventional spin echo sequences, in RARE imaging multiple lines of k-space are acquired within one TR interval instead of only one. Echo train lengths of up to 4 were used in studies by Ross et al [30] and Araya et al [31] without image degradation. This speed up by a factor of 4 reduces the acquisition time per image in our example from approximately 25 min to a reasonable 6 min.…”