Cerebral glucose delivery, transport and metabolism: Theory and modeling using four, three, and two tissue compartments.

Flux equations describing brain D-glucose uptake are presented for up to four tissue compartments: blood, endothelial intracellular space in the blood-brain barrier (BBB), extravascular-extracellular space (EES), and intracellular space. Transport rates are described by Michaelis-Menten kinetics, including half-saturation constants () and maximum rates for transportover the BBB and the cell membrane (CMB). These transport parameters and the maximum rate for hexokinase-catalyzed metabolism () were determined by numerical fitting of the models to both steady-state and dynamic D-glucose uptake data in human gray matter from MRS.

Creatine-weighted imaging in patients with Parkinson's disease.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder involving impaired bioenergetics and mitochondrial dysfunction. Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted therapy, yet human studies have yielded heterogeneous results. This study employs guanidino chemical exchange saturation transfer (GuanCEST) magnetic resonance imaging (MRI), a novel Cr-weighted imaging technique, to evaluate Cr level changes in patients with PD (PwPD) compared to healthy controls (HCs).

AI-driven framework to map the brain metabolome in three dimensions.

High-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics is an emerging field that enables the dissection of the complex metabolic landscape and heterogeneity from a thin tissue section. Currently, spatial metabolism highlights the remarkable complexity in two-dimensional (2D) space and is poised to be extended into the three-dimensional (3D) world of biology.

Dynamic glucose enhanced imaging using direct water saturation.

Purpose: Dynamic glucose enhanced (DGE) MRI studies employ CEST or spin lock (CESL) to study glucose uptake. Currently, these methods are hampered by low effect size and sensitivity to motion. To overcome this, we propose to utilize exchange-based linewidth (LW) broadening of the direct water saturation (DS) curve of the water saturation spectrum (Z-spectrum) during and after glucose infusion (DS-DGE MRI).

Machine learning-based multi-pool Voigt fitting of CEST, rNOE, and MTC in Z-spectra.

Purpose: Four-pool Voigt (FPV) machine learning (ML)-based fitting for Z-spectra was developed to reduce fitting times for clinical feasibility in terms of on-scanner analysis and to promote larger cohort studies. The approach was compared to four-pool Lorentzian (FPL)-ML-based modeling to empirically verify the advantage of Voigt models for Z-spectra.

Methods: Voigt and Lorentzian models were fitted to human 3 T Z-spectral data using least squares (LS) to generate training data for the corresponding ML versions.

In vivo imaging of glycogen in human muscle.

Probing regional glycogen metabolism in humans non-invasively has been challenging due to a lack of sensitive approaches. Here we studied human muscle glycogen dynamics post-exercise with a spatial resolution of millimeters and temporal resolution of minutes, using relayed nuclear Overhauser effect (glycoNOE) MRI. Data at 5T showed a homogeneous distribution of glycogen in resting muscle, with an average concentration of 99 ± 13 mM.

Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal.

MetaVision3D: Automated Framework for the Generation of Spatial Metabolome Atlas in 3D.

High-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics is an emerging field that enables the dissection of the complex metabolic landscape and heterogeneity from a thin tissue section. Currently, spatial metabolism highlights the remarkable complexity in two-dimensional space and is poised to be extended into the three-dimensional world of biology.

In vivo characterization of glycogen storage disease type III in a mouse model using glycoNOE MRI.

Purpose: Glycogen storage disease type III (GSD III) is a rare inherited metabolic disease characterized by excessive accumulation of glycogen in liver, skeletal muscle, and heart. Currently, there are no widely available noninvasive methods to assess tissue glycogen levels and disease load. Here, we use glycogen nuclear Overhauser effect (glycoNOE) MRI to quantify hepatic glycogen levels in a mouse model of GSD III.

Deep learning-based Lorentzian fitting of water saturation shift referencing spectra in MRI.

Purpose: Water saturation shift referencing (WASSR) Z-spectra are used commonly for field referencing in chemical exchange saturation transfer (CEST) MRI. However, their analysis using least-squares (LS) Lorentzian fitting is time-consuming and prone to errors because of the unavoidable noise in vivo. A deep learning-based single Lorentzian Fitting Network (sLoFNet) is proposed to overcome these shortcomings.

Radiofrequency labeling strategies in chemical exchange saturation transfer MRI.

Chemical exchange saturation transfer (CEST) MRI has generated great interest for molecular imaging applications because it can image low-concentration solute molecules in vivo with enhanced sensitivity. CEST effects are detected indirectly through a reduction in the bulk water signal after repeated perturbation of the solute proton magnetization using one or more radiofrequency (RF) irradiation pulses. The parameters used for these RF pulses-frequency offset, duration, shape, strength, phase, and interpulse spacing-determine molecular specificity and detection sensitivity, thus their judicious selection is critical for successful CEST MRI scans.

A numerical human brain phantom for dynamic glucose-enhanced (DGE) MRI: On the influence of head motion at 3T.

Purpose: Dynamic glucose-enhanced (DGE) MRI relates to a group of exchange-based MRI techniques where the uptake of glucose analogues is studied dynamically. However, motion artifacts can be mistaken for true DGE effects, while motion correction may alter true signal effects. The aim was to design a numerical human brain phantom to simulate a realistic DGE MRI protocol at 3T that can be used to assess the influence of head movement on the signal before and after retrospective motion correction.

Ultrafast Z-spectroscopic imaging in vivo at 3T using through-slice spectral encoding (TS-UFZ).

Purpose: Acquisition of high-resolution Z-spectra for CEST or magnetization transfer contrast (MTC) MRI requires excessive scan times. Ultrafast Z-spectroscopy (UFZ) has been proposed to address this; however, the quality of in vivo UFZ spectra has been insufficient. Here, we present a simple approach to improve this.

MRI Detection of Hepatic -Acetylcysteine Uptake in Mice.

This proof-of-concept study looked at the feasibility of using a thiol-water proton exchange (i.e., CEST) MRI contrast to detect in vivo hepatic -acetylcysteine (NAC) uptake.

The relayed nuclear Overhauser effect in magnetization transfer and chemical exchange saturation transfer MRI.

Magnetic resonance (MR) is a powerful technique for noninvasively probing molecular species in vivo but suffers from low signal sensitivity. Saturation transfer (ST) MRI approaches, including chemical exchange saturation transfer (CEST) and conventional magnetization transfer contrast (MTC), allow imaging of low-concentration molecular components with enhanced sensitivity using indirect detection via the abundant water proton pool. Several recent studies have shown the utility of chemical exchange relayed nuclear Overhauser effect (rNOE) contrast originating from nonexchangeable carbon-bound protons in mobile macromolecules in solution.

Detection of electrostatic molecular binding using the water proton signal.

Purpose: Saturation transfer MRI has previously been used to probe molecular binding interactions with signal enhancement via the water signal. Here, we detail the relayed nuclear overhauser effect (rNOE) based mechanisms of this signal enhancement, develop a strategy of quantifying molecular binding affinity, i.e.

Computationally designed dual-color MRI reporters for noninvasive imaging of transgene expression.

Imaging of gene-expression patterns in live animals is difficult to achieve with fluorescent proteins because tissues are opaque to visible light. Imaging of transgene expression with magnetic resonance imaging (MRI), which penetrates to deep tissues, has been limited by single reporter visualization capabilities. Moreover, the low-throughput capacity of MRI limits large-scale mutagenesis strategies to improve existing reporters.

Deep learning-based classification of preclinical breast cancer tumor models using chemical exchange saturation transfer magnetic resonance imaging.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging has shown promise for classifying tumors based on their aggressiveness, but CEST contrast is complicated by multiple signal sources and thus prolonged acquisition times are often required to extract the signal of interest. We investigated whether deep learning could help identify pertinent Z-spectral features for distinguishing tumor aggressiveness as well as the possibility of acquiring only the pertinent spectral regions for more efficient CEST acquisition. Human breast cancer cells, MDA-MB-231 and MCF-7, were used to establish bi-lateral tumor xenografts in mice to represent higher and lower aggressive tumors, respectively.

Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time.

Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1%) and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements.

Mechanism and quantitative assessment of saturation transfer for water-based detection of the aliphatic protons in carbohydrate polymers.

Purpose: CEST MRI experiments of mobile macromolecules, for example, proteins, carbohydrates, and phospholipids, often show signals due to saturation transfer from aliphatic protons to water. Currently, the mechanism of this nuclear Overhauser effect (NOE)-based transfer pathway is not completely understood and could be due either to NOEs directly to bound water or NOEs relayed intramolecularly via exchangeable protons. We used glycogen as a model system to investigate this saturation transfer pathway in sugar polymer solution.