- Advanced MRI Techniques and Applications
- Advanced NMR Techniques and Applications
- Electron Spin Resonance Studies
- Atomic and Subatomic Physics Research
- Lanthanide and Transition Metal Complexes
- Cardiac Imaging and Diagnostics
- MRI in cancer diagnosis
- Nuclear Physics and Applications
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Cardiac Valve Diseases and Treatments
- Nanoplatforms for cancer theranostics
- Cardiac electrophysiology and arrhythmias
- Cybersecurity and Cyber Warfare Studies
- Magnetism in coordination complexes
- ICT Impact and Policies
- Enzyme Structure and Function
- Medical Imaging Techniques and Applications
- NMR spectroscopy and applications
- Medical Imaging and Pathology Studies
- Electrochemical Analysis and Applications
- Solid-state spectroscopy and crystallography
- Inorganic Fluorides and Related Compounds
- COVID-19 Digital Contact Tracing
- Advanced Neuroimaging Techniques and Applications
Moffitt Cancer Center
2021-2024
University of Oxford
2018-2023
GE Global Research (United States)
2023
Oxford BioMedica (United Kingdom)
2021
University of Toronto
2013-2021
John Radcliffe Hospital
2019-2021
Sunnybrook Research Institute
2013-2020
Sunnybrook Health Science Centre
2013-2020
Resonance Research (United States)
2020
Sunnybrook Hospital
2017
Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used longitudinal studies would useful understanding therapeutic approaches target metabolism. Objective: To demonstrate first hyperpolarized 13 C magnetic resonance of human heart. Methods and Results: Four healthy subjects underwent conventional proton followed by spectroscopic acquisition immediately after...
The recent development of hyperpolarized
Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of acidity improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed neutralize acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds CEACAM6, cell-surface protein highly expressed gastrointestinal cancers, allowing cleave endogenous urea into two NH4+ and one CO2, thereby raising local pH. To test synergetic effect...
We report experimental characterization of 17O quadrupole coupling (QC) and chemical shift (CS) tensors for the phenolic oxygen in three l-tyrosine (l-Tyr) compounds: l-Tyr, l-Tyr·HCl, Na2(l-Tyr). This is first time that these fundamental NMR are completely determined oxygens different ionization states. find that, while QC tensor changes very little upon phenol ionization, CS displays a remarkable sensitivity. In particular, isotropic increases by approximately 60 ppm which 6 times larger...
Purpose To provide built‐in off‐resonance correction in time‐resolved, volumetric hyperpolarized 13 C metabolic imaging by implementing a novel dual‐echo 3D echo‐planar (EPI) sequence and reconstruction. Methods A spectral‐spatial pulse for single‐resonance excitation followed EPI readout was implemented to 64 × 8 6 cm 3 coverage at 5 mm nominal resolution. Multiple sources of distortions were encoded using multi‐echo 1 H reference scan. Phase maps computed from the scans combined with bulk...
Purpose To enable large field‐of‐view, time‐resolved volumetric coverage in hyperpolarized 13 C metabolic imaging by implementing a novel data acquisition and image reconstruction method based on the compressed sensing framework. Methods A spectral‐spatial pulse for single‐resonance excitation followed symmetric echo‐planar (EPI) readout was implemented encoding 72 × 18 cm 2 field of view at 5 mm resolution. Random undersampling achieved with blipped z‐gradients during ramp portion readout....
Although current cardiovascular MR (CMR) techniques for the detection of myocardial fibrosis have shown promise, they nevertheless depend on gadolinium-based contrast agents and are not specific to collagen. In particular, diagnosis diffuse fibrosis, a precursor heart failure, would benefit from non-invasive imaging technique that can detect collagen directly. Such method could potentially replace need endomyocardial biopsy, gold standard disease. The objective this study was measure...
Purpose Hyperpolarized [1‐ 13 C]lactate in solution may be a clinically relevant and safe substrate for real time MR investigations of key metabolic pathways. The potential using hyperpolarized magnetic resonance studies cardiac metabolism vivo was explored. Methods Neat C]lactic acid the dynamic nuclear polarization process. Cardiac spectroscopy experiments were performed C]pyruvate solutions. Results A high degree achieved (16.7%). C‐bicarbonate observed rat hearts after either or infused,...
Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that creatine kinase (CK) capacity and flux associated this transition.We recruited 102 participants to 5 groups: moderate (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ≥55% (SevAS-preserved fraction, n=37), LV <55% (SevAS-reduced n=15), healthy volunteers nonhypertrophied hearts normal (normal volunteer, n=30),...
Purpose Develop and test an analytic correction method to correct the signal intensity variation caused by inhomogeneous reception profile of eight‐channel phased array for hyperpolarized 13 C imaging. Theory Methods Fiducial markers visible in anatomical images were attached individual coils provide three dimensional localization receive hardware with respect image frame reference. The coil locations dimensions used numerically model using Biot‐Savart Law. accuracy sensitivity estimation...
Purpose Phosphorus spectroscopy ( 31 P‐MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) adenosine triphosphate (ATP) ratio. We focus on another P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into Pi often obscured by signals from blood 2,3‐diphosphoglycerate (2,3‐DPG). introduce quantify in 14 min without hindrance 2,3‐DPG. Methods Using stimulated...
The extracellular pH (pHe) of solid tumors is often acidic, as a consequence the Warburg effect, and an altered metabolic state associated with malignancy. It has been shown that acidosis can promote tumor progression; thus, many therapeutic strategies have adopted against metabolism; one these involves alkalinization therapies to raise inhibit progression, improve immune surveillance, overcome resistance chemotherapies. Chemical exchange saturation transfer-magnetic resonance imaging...
In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment metabolism in vivo. The pre-polarized administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts imaged using an interleaved sequence designed spectral–spatial pulses flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed tumour, kidney, muscle regions interest. relationship between hyperpolarized explored...
A calibration‐based technique for real‐time measurement of pyruvate polarization by partial integral analysis the doublet from neighbouring J ‐coupled carbon is presented. In vitro calibration data relating C 2 and 1 asymmetries to instantaneous polarizations, respectively, were acquired in blood. The feasibility using determine vivo polarizations was demonstrated rat kidney pig heart spectral data. An approach incorporating this into protocols proposed. Copyright © 2013 John Wiley & Sons, Ltd.
Even at 7 T, cardiac 31 P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal spatial resolutions. Compartment-based reconstruction algorithms such as spectroscopy with linear algebraic modeling (SLAM) spectral localization (SLIM) may improve SNR or reduce time without changes acquisition. Here, we compare the repeatability performance of these compartment-based methods, applied three...
Purpose To investigate the feasibility of performing large FOV hyperpolarized 13 C metabolic imaging using simultaneous multislice excitation. Methods A spectral‐spatial excitation pulse was constructed by cosine modulation and incorporated into a spiral sequence. Phantom in vivo pig experiments were performed to test data acquisition image reconstruction. In cardiac‐gated images pyruvate, bicarbonate, lactate obtained at 1 × cm 3 resolution over 48 24 with 2‐fold acceleration slice...
Purpose For 13 C echo‐planar imaging (EPI) with spectral‐spatial excitation, main field inhomogeneity can result in reduced flip angle and spatial artifacts. A hybrid time‐resolved pulse sequence, multi‐echo EPI, is proposed combining broader passbands for greater off‐resonance tolerance a acquisition to separate signals from potentially co‐excited resonances. Methods The performance of the sequence reconstruction pipeline were evaluated 1 H using series increasingly dilute 1,4‐dioxane...
Purpose 1H MRI is an established diagnostic method that generally relies on detection of water. Imaging specific macromolecules normally accomplished only indirectly through the use paramagnetic tags, which alter water signal in their vicinity. We demonstrate a new approach macromolecular constituents, such as proteins and drug delivery systems, are observed directly quantitatively vivo using 13C-labeled poly(ethylene glycol) (13C-PEG) tags. Methods Molecular imaging 13C-PEG-labeled species...
Purpose Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral‐spatial RF excitation has been shown to form an attractive magnetization‐efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known. Methods In this work, we propose a novel 3D hybrid‐shot spiral sequence which features two constant density regions that permit retrospective reconstruction either spatial or temporal...
Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through creatine kinase reaction is investigated by observing decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification total ATP utilization currently underexplored, as it requires simultaneous inorganic phosphate ( Pi ) and PCr. This challenging, available pulses reduce already-low γ-ATP signal present.Using a hybrid optimal-control Shinnar-Le Roux...
Hyperpolarized (HP) MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since ‐lactate signal levels obtained from HP imaging depend on multiple factors, such as rate of substrate delivery via vasculature, expression level monocarboxylate transporters (MCTs) and dehydrogenase (LDH), local pool size, interpretation metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived...