Announcements Funding CTRFP Awardees ICTS News

ICTS Announces 2022-2023 CTRFP Awardees

(1st row, left to right) Jennifer Alexander-Brett, MD, PhD; Jane Armer, PhD, RN, FAAN; Thomas J. Baranski, MD, PhD; Alex Rene Carter, MD, PhD; Jen Jen Chang, PhD, MPH (2nd row, left to right) Vincenza Cifarelli, PhD; Gautam Dantas, PhD; Brian F Gage, MD, MSc; Mojgan Golzy, PhD; Aditi Gupta, PhD; Catherine Rose Hoyt, PhD, OTD, OTR/L (3rd row, left to right) Aaron N. Johnson, PhD; James G. Krings, MD, MSCI; Xiaowei Li, PhD; Jonathan Daniel Moreno, MD, PhD; Dhiren Patel, MD; Linda Ruth Peterson, MD, FACC, FAHA, FASE (4th row, left to right) Devita Stallings, MSN, PhD, RN; Lulu Sun, MD, PhD; Kwee Thio, MD; Guoqiao Wang, PhD; Yong Wang, PhD; Gregory F. Wu, MD, PhD; Jie Zheng, PhD

Washington University Institute of Clinical and Translational Sciences (ICTS) and The Foundation for Barnes-Jewish Hospital awards 25 investigators as part of the 15th annual Clinical and Translational Research Funding Program (CTRFP). The CTRFP is the largest internal grant funding program of the ICTS. Applicants are required to submit proposals for projects that promote the translation of scientific discoveries into improvements in human health. For 2022, awards were considered across three project categories: clinical/translational, community-engaged research, and biostatistics, epidemiology, and research design.

This year the CTRFP received over 100 letters of intent and awarded over $1.1M for investigator-initiated projects. These grants are supported with funding from the ICTS, The Foundation for Barnes-Jewish Hospital and ICTS partner institutions: Saint Louis University and the University of Missouri-Columbia.

Novel Exosome-Based Biomarker for Diagnosis of Chronic Lung Allograft Rejection

PI: Jennifer Alexander-Brett, MD, PhD
Washington University School of Medicine: Department of Medicine, Division of Pulmonary and Critical Care Medicine

Lung transplant chronic rejection remains challenging to detect prior to development of clinical bronchiolitis obliterans syndrome (BOS). There is a need for diagnostic tools to identify subclinical rejection and preserve allograft function. Recent studies illuminated submucosal gland (SMG) degeneration as a feature of chronic rejection and our transcriptomic analysis on BOS SMG cells revealed downregulation of lactoferrin (LTF), a component of exosomes. This proposal addresses the hypothesis that reduced levels of exosome-associated LTF serves as a biomarker of airway submucosal cell damage and correlates with clinical BOS. Aim 1 will address measurement of exosome-bound LTF in stable post-lung transplant serial bronchial wash (BW) specimens and Aim 2 will compare these results to patients with clinical BOS. The goal of this project is to address a major clinical need through advances in technology at the interface of basic science and patient care to improve outcomes in lung transplantation.

Application of eXplainable Artificial Intelligence for Automatic Stratification/Prioritization of Patient Subpopulations for Deep Understanding of COVID-19 and Cancer Associations in Cerner Database

PI: Jane Armer, PhD, RN, FAAN
University of Missouri – Columbia: Sinclair School of Nursing

Cancer survivors often are immunocompromised and at greater risk of severe consequences (mortality/morbidity) from contracting Coronavirus SARS-CoV-2 (COVID-19). Cancer-related risks include delayed screening, surveillance, diagnosis, treatment, and follow-up, potentially linked to more advanced cancer diagnosis; more invasive and extended cancer treatments; and poorer patient outcomes.  Cerner’s large-scale de-identified Real-World Dataset provides opportunity to apply a sophisticated, novel algorithm to discover associations among medical record and clinical observational data. We will use a unique Deep-and-Wide-Exploratory-Mining (DWEMine) algorithm to discover significant subgroups and contrast patterns within the various cancer diagnostic groups in Part A of the dataset. We will validate the findings using Part B of the dataset. Application of eXplainable-Artificial-Intelligence (XAI) methods for automatic stratification and prioritization of patient subpopulations will provide us a deeper understanding of COVID-19 and cancer associations, leading to improved protocols for cancer screening, surveillance, treatment, and follow-up for those at risk for and diagnosed with COVID-19.

Effectiveness, Safety, and Tolerability of Different Estradiol Dosing Regimens in Transgender Females

PI: Thomas J. Baranski, MD, PhD
Washington University School of Medicine: Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research

Gender affirming hormone therapy (GAHT) is a critical step in achieving feminine features consistent with gender identity in transition-age (18-45 years) transgender females. GAHT facilitates this process by maintaining estradiol levels within the normal cisgender female range while suppressing endogenous testosterone. However, current treatment guidelines are based on treatments used in postmenopausal women and from clinical experiences from experts in the field rather than strong evidence from clinical trials or studies. Moreover, the scientific evidence from randomized trials on the impact of estrogen on metabolic and coagulation factors is deficient. Thus, the current proposal seeks to evaluate the effectiveness, safety and tolerability of estrogen use in transgender females and the degree of testosterone suppression achieved in this population when randomized to two different dosing regimens of sublingual 17 beta-estradiol or transdermal 17 beta-estradiol, in conjunction with spironolactone (antiandrogen).

Gaze Distribution in an Ecologically Valid Task as a Biomarker to Assess Hemi-inattention after Stroke

PI: Alex Rene Carter, MD, PhD
Washington University School of Medicine: Neurology

Where we are looking is generally a good indicator of where our attention is in 3-D space. Unfortunately for many stroke patients, their sense of space can be so severely disrupted that they fail to notice one whole side of space. This “spatial neglect” after stroke gets in the way of people being able to toilet, bathe and dress themselves independently, and generally makes stroke recovery much more difficult. Most tests that exist to detect this spatial neglect are so artificial that treatments that improve test performance in the laboratory may not translate into improvements in the real world. This project uses wearable eye-trackers to see what people with stroke pay attention to while doing routine tasks. This will allow us to test whether different treatments for spatial neglect affect where people are looking and hence whether those treatments are likely to improve real-world functioning in stroke patients.

A Community-based Participatory Research Approach to Increase COVID-19 Vaccine Uptake among African American Families with Children in St. Louis

PI: Jen Jen Chang, PhD, MPH
Saint Louis University, College for Public Health and Social Justice, Epidemiology and Biostatistics

About 22% of all COVID-19 cases in the U.S. are among children and adolescents. The COVID-19 related hospitalization among the pediatric population has significantly increased recently. Data suggest that Black children and adolescents had higher rates of confirmed COVID-19 cases, hospitalization, and intensive care admission than their White counterparts. In St. Louis, the COVID-19 vaccine initiation rate among 12-15-year-olds is about 53% for NH white but only 21% for NH Black children. The study team will mobilize diverse community leaders and partners to bring information, facilitate discussion, build trust, and develop measurable improvement (with future external funding) to address racial disparity in COVID-19 vaccine coverage among African American children and adolescents in St. Louis. The study team will work with community partners and stakeholders to initiate widespread dialogue. We will use what we learn to develop effective strategies for increasing COVID-19 vaccine uptake in African American children and adolescents.

PET Imaging Cardiac Inflammation in CD36-Deficient Individuals

PI: Vincenza Cifarelli, PhD
Washington University School of Medicine

The fatty acid translocase CD36 regulates cardiac function. CD36 genetic deletion in rodents associates with (1) atrioventricular block and bradycardia; (2) increasing risk of sudden death following prolonged fasting and (3) subclinical inflammation in tissues, including the heart. However, the role of CD36 in myocardial remodeling and inflammation, its contribution to heart disease and whether preventive treatment strategies should be used in this population remain controversial due to lack of clinical studies. This application will assess myocardial inflammation in individuals with dysfunctional lipid metabolism using a novel non-invasive positron emission tomography (PET) imaging approach.

Strain Tracking and Genomic Characterization of Pseudomonas Aeruginosa Across Clinical and Environmental Samples in a Healthcare System

PI: Gautam Dantas, PhD
Washington University School of Medicine: Pathology and Immunology  

Healthcare-associated infections (HAIs) are a significant cause of morbidity and mortality. Sink drains in hospitals can harbor antibiotic resistant organism reservoirs that cause HAIs. In a previous study, we identified Pseudomonas aeruginosa (PSAR) strains were widely disseminated across sink drains in a newly-built oncology intensive care unit (ICU) at Barnes Jewish Hospital. These strains were highly-related to isolates from blood stream infections in the same ICU. We also detected these strains in isolates from blood cultures from patients outside of this ICU, suggesting they could be more widespread throughout the hospital. Removal of PSAR reservoirs from the healthcare infrastructure could be crucial in preventing future HAIs. In this study, we propose to 1) investigate the extent of colonization of PSAR strains in clinical specimens and environmental surfaces across the hospital; and 2) develop methods to rapidly detect associations between environmental contaminants and patient specimens to identify targets of future interventions.

Pharmacogenetic Refinement of the Warfarin Dose Using Machine Learning

PI: Brian F Gage, MD, MSc
Washington University School of Medicine: Department of Medicine, Division of General Medical Sciences

We propose to use penalized linear models and machine learning to develop clinical and genotype-guided dosing algorithms for days 7-21 of warfarin therapy.

Classification and Estimation of Cluster-transition Probability

PI: Mojgan Golzy, PhD
University of Missouri – Columbia: School of Medicine, Office of Medical Research

Little is currently known about the impact of bladder cancer diagnosis and treatments on the emotional and physical functioning of patients. In this study, we will implement unsupervised clustering techniques to classify bladder cancer patients with similar level of mental and physical functioning. The mental and physical scores will be measured by the SF-36 health related quality of life instruments from SEER-MHOS data set. We will implement two clustering methods and choose the one with the best performance. We will analyze the association between the identified clusters and the patient characteristics and outcomes. We will estimate the cluster specific survival probability given the patient data, and the cluster-transition probability over a two-year follow-up for patients based on their characteristics such as stage of cancer and type of treatment. The funding of this study is important in advising elderly patients on treatment options for bladder cancer given the patient characteristics.

Prediction Model to Establish the Diagnosis of Superimposed Preeclampsia

PI: Aditi Gupta, PhD
Washington University School of Medicine, Biostatistics

Preeclampsia (PE) is one of four hypertensive conditions of pregnancy, which include chronic hypertension (CHBP), gestational hypertension, and CHBP with superimposed PE. PE is a leading cause of maternal morbidity and mortality, perinatal mortality, fetal growth restriction, and preterm birth. Distinguishing between the four disorders is an important, but challenging, first step in optimizing patient care. CHBP with superimposed PE is particularly challenging to diagnose. Pregnant women with a history of CHBP may have an isolated BP elevation without other symptoms of PE, which are themselves, non-specific. Confirmatory tests require timely, multiple assessments, with attendant patient compliance issues. We aim to use statistical and machine learning methods to conduct a retrospective analysis of patient electronic health records collected during antenatal care to identify trends that can reliably predict superimposed PE in women with CHBP.

Utilization of Developmental Screening and Early Intervention in Sickle Cell Disease

PI: Catherine Rose Hoyt, PhD, OTD, OTR/L
Washington University School of Medicine: Occupational Therapy

In this study, we will quantify the number of children with sickle cell disease (SCD) who have completed developmental screening and been referred for home-based early intervention therapy services. Complications associated with SCD (e.g., infection, pain, stroke) are common in the first years of life. Developmental delays are present in up to 50% of children with SCD before the age of 3 but are rarely screened or diagnosed. When developmental delays are overlooked, children miss a critical opportunity for intervention that could improve their developmental trajectory. Home-based interventions have proven effective in improving developmental outcomes among young children with SCD, but without timely screening and referral, children with SCD are unable to take advantage of these services. In the proposed study, we will quantify the proportion of children who are being overlooked for these services.

A Functional Genomics Approach to Diagnose Rare Genetic Diseases

PI: Aaron N. Johnson, PhD
Washington University School of Medicine: Developmental Biology

Rare genetic disease discovery efforts typically lead to the identification of new disease genes. While there is inherent value in uncovering the genetic basis of disease for diagnosis (e.g., reproductive planning), there is also significant opportunity to gain deep mechanistic or biological insights into disease pathogenesis. PreMIER (Precision Medicine Integrated Experimental Resources) is a WUSTL platform designed to facilitate functional evaluation of human genetic variants in model systems. PreMIER operates as an expert panel that provides consultation services to physicians and researchers regarding suitable model systems for exploring pathogenicity and molecular mechanisms of patient variants. The PreMIER platform has identified 11 cases could be effectively modeled in fruit flies. We propose to develop a pipeline of five functional assays using fruit flies to characterize patient variants in a fast and cost-effective manner. Our functional characterization will provide the first genotype-phenotype correlations for nearly a dozen patients with idiopathic genetic disorders.

Symptom-driven ICS/LABA Therapy for Adolescents with Asthma who are Non-adherent to Daily Maintenance Therapy

PI: James G. Krings, MD, MSCI
Washington University School of Medicine: Department of Medicine, Division of Pulmonary and Critical Care Medicine

Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy given their long-term anti-inflammatory effects. However, many adolescents with asthma are non-adherent to their maintenance ICS inhalers. Acknowledging this problem, guideline bodies recently recommended that adolescents be considered for symptom-driven ICS/long-acting beta-agonist (LABA) inhalers in place of traditional maintenance ICS inhalers (that many patients fail to use) and symptom-based short-acting beta-agonists. With this approach adolescents are exposed to the anti-inflammatory effects of inhaled corticosteroids when utilizing a rescue ICS/LABA inhaler. While this approach has been examined in multiple recent randomized-controlled trials, it has not been explored as a way to ameliorate the detrimental consequences of maintenance inhaler non-adherence. In this study, we aim to (Aim 1) undertake a pilot real-world randomized-controlled trial of symptom-driven ICS/LABA inhalers in maintenance inhaler non-adherent adolescents; and (Aim 2) utilize a dissemination and implementation science conceptual framework to better understand views of this approach.

3D-Printed Antithrombogenic Sutureless Vaso-Lock for Vascular Anastomosis

PI: Xiaowei Li, PhD
Washington University School of Medicine: Plastic and Reconstructive Surgery

Microvascular and vascular anastomosis is the hand-sewing together of blood vessels, and is a foundational surgical skill critical for plastic and reconstructive surgery, transplant surgery, vascular surgery, and more. However, it faces many challenges, such as decade-training in resource-intensive settings and inherent dexterity of the surgeon. Recently, our team has created a unique anastomotic device, Vaso-Lock, as a sutureless coupler. The Vaso-Lock holds free vascular ends together with traction by bristles, delivering consistent, expedious anastomosis. Specifically, we have utilized 3D-printing to prototype these Vaso-Locks with quick adjustments in designs for customization freedom, cost-effective prototyping, and fast production. As for clinical application of Vaso-Lock as a permanent anastomotic device, here we will develop a surface-modification approach to facilitate endothelial cell affinity and anticoagulant abilities of Vaso-Locks. Our long-term goal is to apply antithrombogenic sutureless Vaso-Locks to change the paradigm of surgical training and practice, and improve technical capabilities for vascular anastomosis.

Understanding Proarrhythmic Mechanisms of Cardiac Myopathies: Bridging Patients and iPSC Technologies

PI: Jonathan Daniel Moreno, MD, PhD
Washington University School of Medicine: Department of Medicine, Cardiovascular Division

Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiomyopathy and is the leading cause of sudden cardiac death (SCD) in young people. Though HCM is characterized by mutations in the genes encoding the contractile apparatus (muscle) of the cell, SCD results from electrical disturbances leading to fatal ventricular arrhythmia. Such was the case for M.M., a 6 year-old patient seen in our Pediatric EP clinic, who suffered from a deadly rhythm disturbance as her initial manifestation of disease. How mutations in cardiac muscle contraction manifest initially as a proarrhythmic substrate is unclear. We will generate and characterize iPSC cell lines from M.M., who has two potentially causative HCM mutations, but is phenotypically normal. We will probe this connection using an iPSC platform, optical and high-throughput electrophysiology to define mechanisms behind this deadly phenomenon. This will allow us to tailor SCD risk prediction and design precision therapies for inherited cardiomyopathies.

Neuromodulation with Percutaneous Electrical Nerve Field Stimulation for Children with Cystic Fibrosis Experiencing Chronic Abdominal Pain

PI: Dhiren Patel, MD
Saint Louis University, Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition

Cystic Fibrosis (CF) is a life-long genetic disorder typically diagnosed in childhood. Though it is primarily a lung disease, CF affects many other organ systems. The goal of our study is to address the gastrointestinal (GI) component in CF patients, specifically their chronic abdominal pain. We plan to offer a novel neurostimulation device technology, IB stim, to these patients. This device directly approaches the nerve field on the ear lobe, which is known to transmit signals to the pain controlling areas in the brain. Here it modulates pain sensation and reduces the severity of abdominal pain. IB-stim is approved by the Food and Drug Administration for children 11-18 years with long-standing belly pain. This device has virtually no side effects and does not need any sedation. We plan to evaluate the response of this therapy over four consecutive device placements and monitor improvements in patient’s quality of life.

Development of a Novel Radiotracer of the Sodium Glucose Co-Transporter-2 (SGLT2)

PI: Linda Ruth Peterson, MD, FACC, FAHA, FASE
Washington University School of Medicine: Department of Medicine, Cardiovascular Division

Cancer is the second-leading cause of death in the U.S. Clearly, new strategies are needed to combat this mortal disease. Recently, studies discovered a promising therapeutic pathway: metabolic manipulation. Some human cancer cells, which are highly dependent on glucose use to meet their voracious metabolic needs, are known to upregulate the sodium glucose co-transporter 2 (SGLT2) to increase glucose uptake. Normally, SGLT2 is expressed almost exclusively in the kidney. Identifying whether a cancer expresses SGLT2 using a noninvasive imaging agent could help physicians 1) detect cancer; 2) target vulnerable cancers with SGLT2 inhibitors (SGLT2i’s) and 3) assess response to SGLT2i’s. A novel SGLT2-specific positron emission tomography tracer (Me-4FDG) developed at UCLA has already been used in pilot studies in humans. The aim of this study is to develop Me-4FDG at WUSM and to complete all regulatory requirements to support wide-ranging studies of human cancer diagnosis and treatment with SGLT2i’s.

Engaging African American Communities in the Development of a Hypertension Self-Management App (Pressure Points)

PI: Devita Stallings, MSN, PhD, RN
Saint Louis University, Trudy Busch Valentine School of Nursing

In the United States, hypertension accounts for 50% of the racial differences in mortality between African American and White adults and African Americans (AAs) have the highest prevalence of hypertension in the world. Among AAs aged 20 and older, 58.3% of men and 57.6% of women have hypertension compared to 46% of non-Hispanic Whites. AAs suffer from earlier disease onset, 80% more fatal strokes, 50% more cardiovascular disease, and have 4-fold more kidney failure. Of the 67.8 million Americans with hypertension, 73.9% do not have their hypertension controlled to ≤ 130/80 mmHg. Mobile health interventions that incorporate culturally relevant, individualized, and evidence-based self-management interventions offer promising ways to improve the hypertension disparity that exist in AAs aged 20 and older; however, few studies exist. The major goal of our project is to use a community-based participatory research approach to develop a web-based mobile health app for self-management of hypertension.

Application of a Targeted Gene Sequencing Panel in Molecular Classification of Endometrial Carcinoma

PI: Lulu Sun, MD, PhD
Washington University School of Medicine: Pathology and Immunology

Endometrial carcinomas are the fourth most common cancer in women. Prognosis, surgical management, and postoperative therapy all depend on accurate classification of carcinoma type. However, histologic classification of endometrial carcinomas is poorly reproducible. Recently, molecular subtypes of endometrial carcinomas were discovered that have prognostic and therapeutic significance, but there have been barriers to their clinical implementation. We propose the use of a targeted, next-generation sequencing panel (GatewaySeq) to subtype endometrial carcinomas. We will compare the performance of GatewaySeq to the current gold standard for molecular categorization (the ProMisE algorithm), which employs a combination of immunohistochemistry and single gene sequencing. We will then evaluate whether molecular subtype determined by GatewaySeq correlates with patient outcome. Successful completion of this project will demonstrate the validity of this assay in classifying endometrial carcinomas, and enable its use in routine clinical workup and future clinical trials.

Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy

PI: Kwee Thio, MD
Washington University School of Medicine: Neurology

The 30% of persons with epilepsy who are drug-resistant bear most of the financial and psychosocial costs of this common neurological disorder. An effective, clinically-used treatment for these individuals is the ketogenic diet (KD), a high fat, low carbohydrate diet. Newer variants of the KD including the modified Atkins diet (MAD) and low glycemic index treatment (LGIT) are more palatable than the older versions but are challenging to maintain because they are strict. The MAD and LGIT lower blood glucose and produce mild ketosis. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) such as empagliflozin have become important additions to the armamentarium for treating type 2 diabetes. SGLT2i decrease blood sugar by causing glucosuria, and they induce mild ketosis. These actions raise the possibility that SGLT2i can replace the MAD and LGIT as epilepsy treatments. This pilot, phase I study will determine the feasibility, safety, and tolerability of SGLT2i in adults with epilepsy.

Precision Medicine: Identifying Responders in Failed Phase 2/3 Clinical Trials for Alzheimer Disease

PI: Guoqiao Wang, PhD
Washington University School of Medicine: Biostatistics

Although precision medicine methodology has gained wide-spread interests and implementation in other disease areas, it has not been utilized in Alzheimer Disease (AD) for two major factors: (i) no disease modifying treatments have been approved during the last 2-3 decades until aducanumab; and (ii) treatment effects manifested through amyloid biomarkers have not been accepted by FDA until the accelerated approval of aducanumab. The evolvement of these factors coupled with the similar treatment effects in amyloid biomarker endpoints observed in failed phase 2/3 AD clinical trials ignites the hope to identify subpopulations who benefit most from these treatments using precision medicine methodology. We aim to develop the interaction tree-based subgroup identification method to identify the beneficial subpopulations from some non-aducanumab investigational treatments using several failed phase 2/3 AD trials with ~6000 individual level data. Our proposal pioneers and may potentially catalyze the application of precision medicine methodology in AD clinical trials.

Three-dimensional Noninvasive Electrophysiology Imaging of Human Uterine Peristalsis

PI: Yong Wang, PhD
Washington University School of Medicine: Obstetrics and Gynecology

Although we know a great deal about the hormonal regulation and physiology of the endometrium during the menstrual cycle, we know little about myometrial physiology. Studies have shown spontaneous, mild contractions – termed uterine peristalsis (UP) – vary throughout the phases of the menstrual cycle and may play an important role in fertility and normal menstruation. However, these studies have all been greatly hindered by the limitations of the available technologies. Our objective is to fill this knowledge gap by using a method we developed – electromyometrial imaging (EMMI) – to quantitatively and objectively define the myometrial electrical activity underlying UP in three-dimensions. We will use EMMI to test our central hypothesis that measures of myometrial activity during UP (initiation site, direction, duration, and magnitude) will quantitatively differ depending on the phase of the menstrual cycle and will quantitatively differ between women with and without endometriosis.

Compartmentalized Antibody Production in Autoimmune Demyelinating Diseases of the CNS

PI: Gregory F. Wu, MD, PhD
Washington University School of Medicine: Neurology

Multiple sclerosis (MS) – the quintessential inflammatory demyelinating disease of the central nervous system (CNS) – affects over 700,000 Americans and is a leading cause of disability in young adults. While it has long been recognized that the immune system, particularly the adaptive immune system (T and B cells), mediates neurologic damage, the targets for these immune cells have never been defined. A rare condition related to MS, myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD), is a newly recognized relapsing-remitting neurologic disease that is also characterized by inflammatory demyelination within the CNS. MOGAD patients have episodes of neurologic impairment that can lead to enduring and significant disability. MOGAD is defined in part by the presence of antibodies specific to MOG, a myelin protein expressed within the CNS. We hypothesize that MOGAD is a distinct autoimmune disease, with unique anatomic, neurologic, and immunologic mechanisms that stem from inappropriate targeting of MOG.

Myocardial Oxygen Extraction Fraction Imaging with MRI

PI: Jie Zheng, PhD
Washington University School of Medicine: Radiology, Radiological Science

Imbalance of myocardial oxygen supply and demand precipitates a cascade of physiological changes resulting in ischemic pathology. Myocardial oxygen extraction fraction (mOEF), which relates the biologic coupling of myocardial blood flow (oxygen supply) to oxygen demand, may provide accurate assessment of this balance. We recently developed a new contrast-free cardiovascular magnetic resonance (CMR) mOEF quantification method, with much improved image quality without any image distortion. The objective of this study is to systematically evaluate the reproducibility of this technique and explore its application for the diagnosis of cardiac metabolism dysfunction. In Aim 1, we will validate this method in vivo in 10 healthy controls on different days. In Aim 2, we will perform a pilot translational study in 10 patients with 18F-FDG-PET determined hibernating myocardium. We hypothesize that the viable myocardial segments will have increased resting mOEF, whereas non-viable segments will have significantly reduced resting mOEF.