Structural and Metabolic Brain Imaging

Brain activation is (sometimes) reflected in changes of the acquired MR signal. Depending on the selected acquisition method, these changes may reflect underlying neuronal activation, or just very unspecific changes in local blood oxygenation or flow. The magnetic fingerprint of neuronal activation strongly depends on local physiological processes and on the underlying microscopic composition of the neuronal tissue and microvascular architecture and dynamics. High-resolution structural and quantitative imaging is thus a prerequisite to assess these structural and hemodynamic properties on a mesoscopic level.


1. Quantification of hydroxyl exchange of D‐Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla

Chemical exchange saturation transfer (CEST) MRI enables the indirect detection of metabolites in small concentrations via exchange of protons in functional groups and water protons. CEST effects were observed in vivo for amide protons of proteins, amine protons of glutamate, guanidyl protons of creatine, and also for hydroxyl protons of glycosaminoglycans and myo‐inositol. As hydroxyls of sugars also showed significant CEST effects in vitro, in vivo experiments could be performed to detect the uptake of injected glucose and glucose analogs in animal models using CEST. A major problem is that optimization in vivo is complicated, especially in human subjects, as only a few protocols can be tested reliably during one examination. Moreover, exchange rates for each individual hydroxyl proton of the glucose molecule have not been determined, nor their pH dependence, thus preventing a proper and accurate simulation and investigation of saturation conditions for optimizing the attainable CEST contrast. To overcome this problem a numerical approach is followed in the present work: by quantification of glucose exchange rates at physiological conditions in vitro, a tissue‐like two‐pool model of water and a semi‐solid magnetization transfer (ssMT) can be extended by the determined glucose hydroxyl pools. This in silico pool model is then used in Bloch‐McConnell simulations to gain insight into the expected signal and contrast‐to‐noise of a glucose injection experiment as near as possible to an in vivo experiment.

2. DeepCEST: 9.4 T Chemical exchange saturation transfer MRI contrast predicted from 3 T data - a proof of concept study

Chemical exchange saturation transfer (CEST) allows for indirect detection of solute molecules via exchanging protons that transfer selectively applied saturation to the large water pool in tissue. While studies have been performed at clinical field strengths, CEST effects can be studied more specifically at higher field strengths where peak separation and selective saturation benefit from the increased frequency separation between resonances, proportional to the Larmor frequency. Some of the peaks can be detected separately only at UHF and lead to the understanding that some signals detected at 3 T are actually mixed signals from several resonances. The information is not gone, but just hard to extract, and 3 T signals are still rich in information from different origins.This work follows the approach of using prior UHF knowledge for 3 T evaluation, in this case by applying artificial neural networks to combine these different data. The proposed neural network is trained using 3 T Z‐spectra as an input and 9.4 T CEST parameters as a target. Thus, it is trained to predict 9.4 T CEST contrasts from a Z‐spectrum measured at 3 T. In a way, this is the most direct approach of using 9.4 T prior knowledge for 3 T data evaluation. While application of neural networks in the field of MR has gained more interest in recent years, the presented approach represents a first step toward application in CEST MRI and is a rather simple approach. A multilayer perceptron is used to combine coregistered data acquired at a 9.4 T human MRI scanner and a 3 T clinical scanner.

3. 3D gradient echo snapshot CEST MRI with low power saturation for human studies at 3T

For clinical implementation, a chemical exchange saturation transfer (CEST) imaging sequence must be fast, with high signal-to-noise ratio (SNR), 3D coverage, and produce robust contrast. However, spectrally selective CEST contrast requires dense sampling of the Z-spectrum, which increases scan duration. This project proposes a compromise: using a 3D snapshot gradient echo (GRE) readout with optimized CEST presaturation, sampling, and postprocessing, highly resolved Z-spectroscopy at 3T is made possible with 3D coverage at almost no extra time cost.
A 3D snapshot CEST sequence was optimized for low-power CEST MRI at 3T. Pulsed saturation was optimized for saturation power and saturation duration. Spectral sampling and postprocessing (B0 correction, denoising) was optimized for spectrally selective Lorentzian CEST effect extraction. Reproducibility was demonstrated in 3 healthy volunteers and feasibility was shown in 1 tumor patient.
Low-power saturation was achieved by a train of 80 pulses of duration tp = 20 ms (total saturation time tsat = 3.2 seconds at 50% duty cycle) with B1 = 0.6 μT at 54 irradiation frequency offsets. With the 3D snapshot CEST sequence, a 180 × 220 × 54 mm field of view was acquired in 7 seconds per offset. Spectrally selective CEST effects at +3.5 and –3.5 ppm were quantified using multi-Lorentzian fitting. Reproducibility was high with an intersubject coefficient of variation below 10% in CEST contrasts. Amide and nuclear overhauser effect CEST effects showed similar correlations in tumor and necrosis as show in previous ultra-high field work.

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