Optimization of flow‐sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain

Abstract

Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow-sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain.

Imaging Brain Deoxyglucose Uptake and Metabolism by Glucocest MRI

“…The more rapid fall in the glucoCEST signal compared with the 2DG6P signal in 31 P MRS spectra can be ascribed to several factors, including the sensitivity to detection, anesthesia and further metabolism of 2DG6P. First, the more rapid decrease to baseline compared with that reported in the 13 C MRS literature 8 may be due to restricted in vivo sensitivity of glucoCEST in our experiments; specifically, the glucoCEST signal arises from exchange of protons on the 2DG and 2DG6P molecules with that on water, and this rate is sensitive to the molecular environment including pH, temperature, and the presence of other solutes. Unlike the in vitro conditions, the presence of other solutes in vivo will alter the -OH exchange properties and hence the CEST signal.…”

“…Unlike the in vitro conditions, the presence of other solutes in vivo will alter the -OH exchange properties and hence the CEST signal. To better determine the amount of 2DG6P, we also conducted high-resolution 13 C spectroscopy in brain extracts at several time points after 2DG injection. In the preliminary experiment (data not shown), we found a very high amount of 13 C-2DG6P at 50 minutes, which decreased to near the level of 5 minutes at 80 minutes after 2DG injection, which suggested that the 2DG6P may decrease faster than that measured by 31P MRS. We also observed a new peak at B184.2 p.p.m.…”

“…High-resolution 13 C NMR of brain extract would be a method to determine the amount of various 2DG metabolites under the similar experimental condition. Together with in vitro CEST z-spectra measure of all metabolites, we would be able to clarify their contributions to the detected glucoCEST signal.…”

“…Cerebral blood flow (CBF) was measured using an optimized flow-sensitive alternated inversion recovery (FAIR) arterial spin labeling with repetition time ¼ 20 seconds, echo time ¼ 21 milliseconds, averaging ¼ 4, and multiple values of TI: viz., 50, 200, 500, 800, 1,400, 1,700, 2,000, 3,000, 4,000, and 5,000 milliseconds. 13 …”

“…Nuclear magnetic resonance (NMR) has also been used to detect 2DG, 2DG6P, and other sugars. The resonances of 13 C-labeled 2DG and its metabolite, 2DG6P, are well resolved in 13 C NMR spectra and thus enable estimation of the metabolic rate of glucose in vivo. 7,8 These earlier studies showed that high doses (up to 0.5 g/kg) of 2DG are well tolerated by animals and reveal reaction kinetics similar to those of 14 C-2DG experiments.…”