R01HL151686

Noninvasive Measurement of Oxygenation Using Quantitative Susceptibility Mapping - Project Summary/Abstract

The goal of this research is to develop cardiac quantitative susceptibility mapping (QSM) for non-invasive measurement of blood oxygen saturation, towards the long-term objective of improving early diagnosis, therapeutic decision-making, and clinical outcomes for patients with pulmonary hypertension (PH).

PH is a progressive and life-shortening disorder affecting approximately 10% of adults over the age of 65. Early diagnosis and physiologic monitoring are critically important as PH can become irreversible in its later stages. Impaired oxygenation of the lungs and heart chambers, known as cardiac oxygenation, is a key manifestation of PH that impacts symptoms and clinical outcomes.

Increased pulmonary arterial pressure in PH impairs pulmonary oxygen exchange, leading to a decrease in the delivery of oxygenated blood to the left heart. Systemic cardiac output is often compromised in PH, resulting in a larger differential blood oxygen saturation between the left and right heart. Currently, invasive catheterization (cath) is used to measure cardiac oxygenation, but it comes with procedural risks, ionizing radiation exposure, and is impractical for early diagnosis and serial monitoring. Therefore, a non-invasive method to accurately measure blood oxygenation would be of substantial utility.

MRI is well-suited for PH assessment as it enables integrated evaluation of pulmonary anatomy, pressure, as well as cardiac function and remodeling. However, blood oxygenation is a key gap in MRI evaluation of PH due to limitations in current pulse sequence technology, rather than fundamental MRI physics. It is well-known that deoxygenation changes the magnetic susceptibility of blood, and these changes have traditionally been probed using the transverse relaxation time (T2) of the MR signal. However, this requires patient-specific calibration that is difficult in clinical practice. In contrast, QSM relies on the phase of the MR signal to directly measure susceptibility and thus cardiac oxygenation.

We have obtained highly encouraging preliminary data for QSM measurement of cardiac blood oxygenation, with close agreement between QSM and oxygenation measured invasively. We have identified key challenges for developing cardiac QSM, including motion suppression and prolonged scan times. The current research proposes to develop an accelerated cardiac QSM method and to test QSM in relation to oxygenation on invasive cath, as well as effort tolerance and clinical prognosis.

The study aims are as follows:
1. Develop accelerated cardiac QSM using free-breathing acquisition and optimized reconstruction.
2. Test accelerated and current cardiac QSM among PH patients in comparison to T2-based cardiac oxygenation and the reference standard of invasive cardiac catheterization.
3. Determine whether cardiac QSM stratifies clinical severity and predicts PH disease progression.

The expected outcome of this research is a non-invasive method for measuring cardiac oxygenation, a critically important marker in PH that currently relies on invasive testing. Given the increasing prevalence and therapeutic options for this serious condition, non-invasive oxygenation assessment by cardiac QSM holds broad significance towards the goal of early diagnosis, therapy optimization, and improved clinical outcomes for millions of patients with PH.

Weill Medical College Of Cornell University

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

New York United States

State-Wide

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 568% from $700,288 to $4,679,068.