Publications by authors named "Peter C M Van Zijl"

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.

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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.

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  • There is a growing need for non-invasive methods to monitor glycogen storage diseases (GSD), specifically utilizing saturation transfer (ST) MRI to observe changes in muscle glycogen in a GSD II mouse model.
  • The research involved measuring various metabolites in the skeletal muscles of both healthy and GSD II mice at different ages, assessing the accumulation and levels of muscle glycogen and energy metabolites.
  • Results showed that while glycogen accumulation increased in younger GSD II mice, it plateaued in adults, indicating potential biomarkers for monitoring disease progression and treatment efficacy in GSDs.
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  • Dynamic glucose enhanced (DGE) MRI, using techniques like CEST or CESL, aims to analyze glucose uptake but faces challenges with low sensitivity and motion artifacts.
  • The new method proposed, called DS-DGE MRI, leverages linewidth broadening in water saturation spectra during glucose infusion to improve measurements.
  • Initial tests on brain tumor patients show that DS-DGE MRI produces detailed area-under-the-curve maps that effectively highlight tumor regions, indicating its potential over existing imaging techniques.
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  • The study explores the use of ultrafast Z-spectroscopy (UFZ) MRI at 3T to assess oxidative phosphorylation (OXPHOS) in human skeletal muscle during exercise.
  • UFZ MRI techniques were tested on five healthy participants, revealing significant changes in metabolic signals post-exercise, which were further refined through pH correction methods.
  • Results indicate that UFZ MRI can effectively reduce acquisition time and provides reliable metrics for mitochondrial function, emphasizing the importance of pH correction for accurate OXPHOS measurement.
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The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

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Background: Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases.

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Iron Dextran is a widely used iron oxide compound to treat iron-deficiency anemia patients in the clinic. Similar to other iron oxide compounds such as Ferumoxytol, it can also be used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent due to its strong iron-induced T2 and T2* shortening effects. In this study, we seek to evaluate the feasibility of using Iron Dextran enhanced multi-echo susceptibility weighted imaging (SWI) MRI at 7T to image arterial and venous blood vessels in the human brain.

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  • The study aimed to examine how compartmental anisotropy influences filtered exchange imaging (FEXI) in white matter by measuring FEXI signals from five healthy volunteers using various diffusion filter and detection methods.
  • The results revealed a significant variation in apparent exchange rates (AXR) and filter efficiencies based on the orientation of the filters relative to white matter fibers, indicating a complex interaction between intra-cellular and extra-cellular compartments.
  • The conclusion stresses the need for models in FEXI that consider this anisotropy, as the findings suggest intricate relationships between AXR values and biological properties of water in white matter, which may affect how we interpret FEXI results.
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Purpose: To investigate the effect of inhaled oxygen level on dynamic glucose enhanced (DGE) MRI in mouse brain tissue and CSF at 3 T.

Methods: DGE data of brain tissue and CSF from mice under normoxia or hyperoxia were acquired in independent and interleaved experiments using on-resonance variable delay multi-pulse (onVDMP) MRI. A bolus of 0.

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Purpose: The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain.

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Purpose: This work is to investigate the microstructure-induced frequency shift in white matter (WM) with crossing fibers and to separate the microstructure-related frequency shift from the bulk susceptibility-induced frequency shift by model fitting the gradient-echo (GRE) frequency evolution for potentially more accurate quantitative susceptibility mapping (QSM).

Methods: A hollow-cylinder fiber model (HCFM) with two fiber populations was developed to investigate GRE frequency evolutions in WM voxels with microstructural orientation dispersion. The simulated and experimentally measured TE-dependent local frequency shift was then fitted to a simplified frequency evolution model to obtain a microstructure-related frequency difference parameter ( ) and a TE-independent bulk susceptibility-induced frequency shift ( ).

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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.

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  • The study evaluates the feasibility of using CEST-based creatine mapping in the brain at a magnetic field strength of 3T, focusing on guanidino protons.
  • Wild type and genetically modified mice with low creatine concentrations were analyzed to understand contributions to the GuanCEST signal and to quantify creatine's proton exchange rates.
  • Results indicate a clear Guan proton peak and suggest that CEST mapping can effectively detect changes in intracellular pH and creatine concentration in the brain.
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Accumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic susceptibility contrast (DSC) MRI for blood vessels and DSC MRI-in-the-cerebrospinal fluid (CSF) (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan offers advantages such as a halved scan time and contrast dosage.

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Purpose: The most-used 3D acquisitions for ASL are gradient and spin echo (GRASE)- and stack-of-spiral (SOS)-based fast spin echo, which require multiple shots. Alternatively, turbo FLASH (TFL) allows longer echo trains, and SOS-TFL has the potential to reduce the number of shots to even single-shot, thus improving the temporal resolution. Here we compare the performance of 3D SOS-TFL and 3D GRASE for ASL at 3T.

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Huntington's disease (HD) is a neurodegenerative disorder that presents with progressive motor, mental, and cognitive impairment leading to early disability and mortality. The accumulation of mutant huntingtin protein aggregates in neurons is a pathological hallmark of HD. The glymphatic system, a brain-wide perivascular network, facilitates the exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF), supporting interstitial solute clearance including abnormal proteins from mammalian brains.

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The hierarchically organized structures of the medial temporal lobe are critically important for episodic memory function. Accumulating evidence suggests dissociable information processing pathways are maintained throughout these structures including in the medial and lateral entorhinal cortex. Cortical layers provide an additional dimension of dissociation as the primary input to the hippocampus derives from layer 2 neurons in the entorhinal cortex, whereas the deeper layers primarily receive output from the hippocampus.

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T2-prepared (T2prep) blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an alternative fMRI approach developed to mitigate the susceptibility artifacts that are typically observed in brain regions near air-filled cavities, bleeding and calcification, and metallic objects in echo-planar-imaging (EPI) based fMRI images. Here, T2prep BOLD fMRI was evaluated in an event-related paradigm for the first time. Functional experiments were performed using gradient-echo (GRE) EPI, spin-echo (SE) EPI, and T2prep BOLD fMRI during an event-related visual task in 10 healthy human subjects.

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MR images of the effective relaxation rate R* and magnetic susceptibility χ derived from multi-echo T*-weighted (T*w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R* and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R* and χ and analyze the effects from motion, spatial resolution, and cortical orientation.

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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.

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Article Synopsis
  • Mannitol is used to reduce intracranial pressure and create osmotic blood-brain barrier openings, but a safer, non-invasive monitoring method for its dosing is needed.
  • The study developed a label-free MRI technique, utilizing Chemical Exchange Saturation Transfer (CEST), to measure mannitol levels in the brain after administration in rat models.
  • Results showed that CEST MRI effectively detected mannitol in the brain, with high doses leading to accumulation, and this method could help optimize mannitol usage for enhanced safety and effectiveness in clinical settings.
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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.

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Dynamic glucose-enhanced (DGE) MRI is used to study the signal intensity time course (tissue response curve) after D-glucose injection. D-glucose has potential as a biodegradable alternative or complement to gadolinium-based contrast agents, with DGE being comparable with dynamic contrast-enhanced (DCE) MRI. However, the tissue uptake kinetics as well as the detection methods of DGE differ from DCE MRI, and it is relevant to compare these techniques in terms of spatiotemporal enhancement patterns.

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