A5046626863- Advanced NMR Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Advanced MRI Techniques and Applications
- Glioma Diagnosis and Treatment
- MRI in cancer diagnosis
- Atomic and Subatomic Physics Research
- Electron Spin Resonance Studies
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Brain Metastases and Treatment
- Lung Cancer Research Studies
- Genomic variations and chromosomal abnormalities
- Genetic Syndromes and Imprinting
- Cardiomyopathy and Myosin Studies
- Blood Coagulation and Thrombosis Mechanisms
- Hemophilia Treatment and Research
- Body Composition Measurement Techniques
- Brain Tumor Detection and Classification
- Enzyme Structure and Function
- Ferroptosis and cancer prognosis
- Advanced Neuroimaging Techniques and Applications
- Ocular Diseases and Behçet’s Syndrome
- Sparse and Compressive Sensing Techniques
- Nutrition, Genetics, and Disease
- Atrial Fibrillation Management and Outcomes
Regeneron (United States)
2022-2025
Sunnybrook Health Science Centre
2015-2023
University of Toronto
2015-2023
Sunnybrook Research Institute
2016-2023
Health Sciences Centre
2015-2022
Sunnybrook Hospital
2020
St. Michael's Hospital
2016
General Electric (Canada)
2016
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...
Abstract Rare coding variants that substantially affect function provide insights into the biology of a gene 1–3 . However, ascertaining frequency such requires large sample sizes 4–8 Here we present catalogue human protein-coding variation, derived from exome sequencing 983,578 individuals across diverse populations. In total, 23% Regeneron Genetics Center Million Exome (RGC-ME) data come African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The includes more...
Lactate is now recognized as an important intermediate in brain metabolism, but its role still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected 13C-pyruvate over whole using a new imaging method, hyperpolarized 13C MRI (N = 14, ages 23 to 77). Segmenting 13C-lactate images into atlas regions revealed pattern that was preserved across individuals. Higher signal observed cortical grey matter compared white highest...
Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with at exome-wide significance. We show 6-fold larger effect fat-distribution rare coding variants compared fine-mapped common alleles, enrichment expressed adipose tissue causal partial lipodystrophies, evidence sex-dimorphism....
Atrial fibrillation (AF) has a substantial genetic component. The importance of polygenic risk is well established, while the contribution rare variants to disease warrants characterization in large cohorts.
Abstract In this study, hyperpolarized 13 C MRI (HP‐ MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized C‐pyruvate administered healthy aging individuals ( N = 35, ages 21–77) whole‐brain spatial distributions C‐lactate C‐bicarbonate production were measured. Linear mixed‐effects regressions performed compute regional percentage change per decade, showing a significant reduction both normalized age: decade for C‐bicarbonate. Certain...
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....
Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume enhancement on serial MRI scans which may lag true by weeks or months.Patients (N = 11) were scanned using hyperpolarized [Formula: see text]C prior treatment stereotactic (SRS). The status each lesion was then recorded at six months post-treatment follow-up (or the time death).The positive predictive...
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...
Abstract Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets variants within gene into single score that is then tested association. Typically, range scores calculated across annotation classes frequency bins. Correlation between these can complicate the multiple testing correction hamper interpretation results. We introduce new method called Sparse Burden Association Test (SBAT) joint set under assumption...
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...
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...
Asymmetric in-plane k-space sampling of EPI can reduce the minimum achievable TE in hyperpolarized 13C with spectral-spatial radio frequency pulses, thereby reducing T2* weighting and signal-losses. Partial Fourier image reconstruction exploits approximate Hermitian symmetry data be applied to asymmetric sets synthesize unmeasured data. Here we tested whether application partial would improve spatial resolution from [1- ]pyruvate scans human brain.Fifteen healthy control subjects were imaged...
Abstract Background The peritumoral region (PTR) of glioblastoma (GBM) appears as a T2W-hyperintensity and is characterized by microscopic tumor edema. Infiltrative low grade glioma (LGG) comprises cells that seem similar to GBM PTR on MRI. work here explored if radiomics-based approach can distinguish between LGG PTR, which have future implications existing treatment paradigms. Methods Patients with imaged using 1.5 T MRI were included in the study. Image data from cases manually segmented...
An end-to-end pipeline was developed that processes whole-body Dixon MRI data sets from UK Biobank and corrects for overlapping slices, inhomogeneous signal intensities, fat-water swaps to produce high quality 3D sets. Segmentation maps subcutaneous/visceral fat left/right thigh muscles these were then produced using neural networks, muscle volume phenotypes extracted. The Jaccard index the validation 93.3% segmentation 96.9% segmentation. Excellent correspondence obtained with extracted...