Optimized quantitative mapping of cardiopulmonary oscillations using hyperpolarized <sup>129</sup> Xe gas exchange MRI: Digital phantoms and clinical evaluation in CTEPH.
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2024-04
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Abstract
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The interaction between 129 Xe atoms and pulmonary capillary red blood cells provides cardiogenic signal oscillations that display sensitivity to precapillary and postcapillary pulmonary hypertension. Recently, such oscillations have been spatially mapped, but little is known about optimal reconstruction or sensitivity to artifacts. In this study, we use digital phantom simulations to specifically optimize keyhole reconstruction for oscillation imaging. We then use this optimized method to re-establish healthy reference values and quantitatively evaluate microvascular flow changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE).Methods
A six-zone digital lung phantom was designed to investigate the effects of radial views, key radius, and SNR. One-point Dixon 129 Xe gas exchange MRI images were acquired in a healthy cohort (n = 17) to generate a reference distribution and thresholds for mapping red blood cell oscillations. These thresholds were applied to 10 CTEPH participants, with 6 rescanned following PTE.Results
For undersampled acquisitions, a key radius of 0.14kmax$$ 0.14{k}_{\mathrm{max}} $$ was found to optimally resolve oscillation defects while minimizing excessive heterogeneity. CTEPH participants at baseline showed higher oscillation defect + low (32 ± 14%) compared with healthy volunteers (18 ± 12%, p < 0.001). For those scanned both before and after PTE, oscillation defect + low decreased from 37 ± 13% to 23 ± 14% (p = 0.03).Conclusions
Digital phantom simulations have informed an optimized keyhole reconstruction technique for gas exchange images acquired with standard 1-point Dixon parameters. Our proposed methodology enables more robust quantitative mapping of cardiogenic oscillations, potentially facilitating effective regional quantification of microvascular flow impairment in patients with pulmonary vascular diseases such as CTEPH.Type
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Lu, Junlan, Fawaz Alenezi, Elianna Bier, Suphachart Leewiwatwong, David Mummy, Sakib Kabir, Sudarshan Rajagopal, Scott Robertson, et al. (2024). Optimized quantitative mapping of cardiopulmonary oscillations using hyperpolarized <sup>129</sup> Xe gas exchange MRI: Digital phantoms and clinical evaluation in CTEPH. Magnetic resonance in medicine, 91(4). pp. 1541–1555. 10.1002/mrm.29965 Retrieved from https://hdl.handle.net/10161/34043.
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Scholars@Duke
Fawaz Alenezi
David Mummy
Assistant Professor of Radiology in the Driehuys Lab (Xenon MRI Service Center).
My research interest is clinical applications of hyperpolarized Xenon-129 MRI in various pulmonary diseases, including asthma, COPD, and interstitial lung disease.
Sudarshan Rajagopal
I am a physician-scientist with a research focus on G protein-coupled receptor signaling in inflammation and vascular disease and a clinical focus on pulmonary vascular disease, as I serve as Co-Director of the Duke Pulmonary Vascular Disease Center. My research spans the spectrum from clinical research in pulmonary vascular disease, to translational research in cardiovascular disease, to the basic science of receptor signaling.
Our basic science research focuses on understanding and untapping the signaling potential of G protein-coupled receptors (GPCRs) to regulate inflammation in vascular disease. GPCRs are the most common transmembrane receptors in the human genome (over 800 members) and are some of the most successful targets for drug therapies. While it has been known for some time that these receptors signal through multiple downstream effectors (such as heterotrimeric G proteins and multifunctional beta arrestin adapter proteins), over the past decade it has been better appreciated that these receptors are capable of signaling with different efficacies to these effectors, a phenomenon referred to as “biased agonism”. Ligands can be biased, by activating different pathways from one another, and receptors can be biased, by signaling to a limited number of pathways that are normally available to them. Moreover, this phenomenon also appears to be common to other transmembrane and nuclear receptors. While a growing number of biased agonists acting at multiple receptors have been identified, there is still little known regarding the mechanisms underlying biased signaling and its physiologic impact. We use multiple approaches to probe these signaling mechanisms, including in-house pharmacological assays, advanced phosphoproteomics and single cell RNA sequencing.
Our translational research is focused on studying signaling in different forms of pulmonary hypertension (PH), a disease of the pulmonary vasculature that results in right heart failure. We have identified novel molecular mechanisms that contribute to the development of pulmonary arterial hypertension (PAH), a disease of the pulmonary arterioles. We have also used single cell RNA sequencing to identify the cell types and signaling pathways that contribute to chronic thromboembolic pulmonary hypertension (CTEPH).
Lastly, our clinical research program focuses on the application of novel imaging technologies for diagnosis, prognosis and management of PH. Most notably, this includes the application of hyperpolarized Xenon MRI, in collaboration with Dr. Bastiaan Driehuys in the Department of Radiology, to characterizing the physiological basis of gas exchange and hemodynamic abnormalities across all forms of PH. In collaboration with Dr. Fawaz Alenezi, we have applied advanced echo approaches for the management of PH.
Scott Robertson
Bastiaan Driehuys
Our research focuses on magnetic resonance imaging (MRI) research with hyperpolarized 129Xe gas. We are at at the forefront of developing this novel technology for imaging the lungs of patients with pulmonary disease. We currently have multiple, ongoing NIH and industry-sponsored studies invovling this technique. Hyperpolarization is a laser-based process that enhances the MRI signal of xenon gas by a factor of 100,000 to allow for high-resolution, non-invasive MRI of pulmonary function. In addition to our research program, this technology was recently FDA approved and efforts are underway to implement it clinically.
Current studies are applying 129Xe MRI for early diagnosis and monitoring of interstitial and pulmonary vascular diseases. Our group, which is comprised of MRI scientists and radiologists, works closely with colleagues in pulmonary medicine. Our laboratory provides research opportunities to Ph.D., Masters, and medical students as well as select undergraduate students.
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