Document text
Principal Investigator: Bastiaan Driehuys
Organization: DUKE UNIVERSITY
Fiscal Year: 2024
Award: $744,470
Funding agency: National Heart Lung and Blood Institute
Project Summary/Abstract
Dyspnea (shortness of breath) is among the most common reasons for seeking medical attention. It has a
prevalence rivaling chronic pain and accounts for 10% of emergency room visits. Dyspnea workups involve
extensive diagnostic testing, with high cost, and a slow time to diagnosis. The burden of dyspnea will further
increase as more patients present with symptoms from long COVID. 129Xe MRI provides a promising solution
with its comprehensive, non-invasive, and rapid imaging of lung function. Enabled by its solubility and tissue-
dependent chemical shift, 129Xe probes diffusive transfer from the distal airspaces through the pulmonary
interstitium (membrane) to the capillary red blood cells (RBCs); this provides a 3D decomposition of the drivers
of gas exchange. However, to fully evaluate dyspnea, we must address pulmonary hypertension (PH) and
hypoxia. We do this by quantifying cardiogenic RBC signal oscillations, which can differentiate pre- and post-
capillary PH and exploiting the 129Xe-RBC chemical shift to interrogate mean capillary blood oxygenation. But to
incorporate these powerful 129Xe-RBC biomarkers, we must know how they are affected hemoglobin, changing
alveolar oxygen tension and how they respond to changes in pulmonary vascular flow. Our long-term goal is to
develop a 5-min, comprehensive, 129Xe MRI/MRS exam that reveals all the treatable traits of dyspnea. We bring
a track-record of pioneering studies, advanced acquisition, reconstruction and analysis methods, and
experienced clinician co-investigators who can access the necessary patient populations and comparative
clinical assessments. The objective of this renewal is to demonstrate interventions that change each of the three
129Xe-RBC related biomarkers – RBC transfer, cardiogenic oscillations, and chemical shift. Our central
hypothesis is that by employing appropriate patient populations and carefully selected interventions, each of
these 129Xe-RBC markers can be modified in a way that solidifies our understanding of them for clinical decision
making. The rationale for the proposed research is to advance these biomarkers into multi-center clinical trials
to expand upon anticipated FDA approval for 129Xe ventilation MRI. This work is relevant to the NIH Mission of
improving health by developing and accelerating the application of biomedical technologies. We will pursue three
Specific Aims: 1) Establish and validate a hemoglobin correction for 129Xe MRI, 2) determine the effect of oxygen
administration on 129Xe MRI/MRS Metrics, and 3) measure longitudinal therapeutic change in acute and chronic
pulmonary embolism. Completion of these aims will 1) establish understanding of the RBC-associated 129Xe
biomarkers, 2) how they respond to therapy, and 3) set the stage for broader studies of O2 therapy. The proposed
approach is innovative because it uses novel technologies, patient groups and interventions to uncover the
physiological drivers of dyspnea. It is significant because it will enable development of a single 5-minute 129Xe
MRI/MRS exam that can efficiently assess the multiple possible etiologies of breathlessness.
Terms: <3-D><3-Dimensional><3D><Acceleration><Acute><Address><Affect><After Care><After-Treatment><Aftercare><Alveolar><Anemia><Anticoagulation><Apheresis><Biological Markers><Biomedical Technology><Blood Component Removal><Blood Vessels><Blood capillaries><Blood donor><Blood erythrocyte><Blood flow><Body Tissues><Breathlessness><CAT scan><CT X Ray><CT Xray><CT imaging><CT scan><Carbon Monoxide><Cardiac><Cardiopulmonary><Caring><Causality><Cell Communication and Signaling><Cell Signaling><Chemicals><Chronic><Clinical assessments><Clotting><Coagulation><Coagulation Process><Computed Tomography><Defect><Development><Diagnosis><Diagnostic tests><Diffuse><Diffusion><Disabling><Disease><Disease Progression><Disorder><Distal><Distress><Dizziness><Dyspnea><ED care><ED visit><ER care><ER visit><Early Diagnosis><Emergency Care><Emergency Department care><Emergency Room care><Emergency care visit><Emergency department visit><Emergency health care><Emergency healthcare><Emergency hospital visit><Emergency medical care><Emergency room visit><Erythrocytes><Erythrocytic><Etiology><Evaluation><Exercise Test><Exhibits><Gases><Goals><Health><Hemapheresis><Hemoglobin><Image><Interstitial Lung Diseases><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Investigators><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Lung><Lung Diseases><Lung Function Tests><Lung Respiratory System><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Marrow erythrocyte><Measurable><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Membrane><Methods><Mission><Modeling><Multi-Institutional Clinical Trial><Multi-center clinical trial><Multi-site clinical trial><Multicenter clinical trial><Multisite clinical trial><NIH><NMR Imaging><NMR Tomography><National Institutes of Health><Neuromuscular Diseases><Nuclear Magnetic Resonance Imaging><O element><O2 element><Operative Procedures><Operative Surgical Procedures><Outcome><Oxygen><Oxygen Inhalation Therapy><Oxygen Therapy Care><Patients><Pheresis><Physiologic><Physiological><Population><Position><Positioning Attribute><Prevalence><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Embolism><Pulmonary Gas Exchange><Pulmonary Hypertension><Pulmonary function tests><Pulmonary imaging><QOL><Quality of life><Red Blood Cells><Red Cell><Research><Research Personnel><Research Resources><Researchers><Resources><Selection for Treatments><Shortness of Breath><Signal Transduction><Signal Transduction Systems><Signaling><Solubility><Surgical><Surgical Interventions><Surgical Procedure><Symptoms><Techniques><Technology><Testing><Therapeutic><Therapeutic Trials><Time><Tissues><Tomodensitometry><Transfusion><United States National Institutes of Health><Visualization><Warburg Therapy><Work><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><Zeugmatography><base><bases><bio-markers><biologic marker><biological signal transduction><biomarker><blood corpuscles><capillary><catscan><causation><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><chronic pain><chronic thromboembolic pulmonary hypertension><clinical care><clinical decision-making><comparative><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><cost><deconditioning><developmental><diffused><diffuses><diffusing><diffusions><disease causation><disease of the lung><disorder of the lung><early detection><experience><frailty><imaging><improved><innovate><innovation><innovative><insight><interstitial><interventional strategy><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><lung disorder><lung function><lung hypoxia><lung imaging><lung scanning><medical attention><membrane structure><myoneural disorder><neuromuscular degenerative disorder><neuromuscular disorder><new technology><non-contrast CT><noncontrast CT><noncontrast computed tomography><novel technologies><oxygen administration><oxygen therapy><oxygen transport><patient population><persistent COVID-19><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post treatment><post-acute phases of COVID-19><prolonged COVID-19 symptoms><public health relevance><pulmonary><pulmonary function><pulmonary hypoxia><reconstruction><response biomarker><response markers><selection of treatment><surgery><therapy selection><three dimensional><tool><trait><treatment selection><uptake><vascular><ventilation>