Review Review of Hyperpolarized Pulmonary Functional 129Xe MR for Long-COVID, 2023, Wild et al.

[SNT Gatchaman]

Review of Hyperpolarized Pulmonary Functional 129Xe MR for Long-COVID
Jim M. Wild; Fergus V. Gleeson; Sarah Svenningsen; James T. Grist; Laura C. Saunders; Guilhem J. Collier; Maksym Sharma; Sam Tcherner; Ali Mozaffaripour; Alexander M. Matheson; Grace Parraga

The respiratory consequences of acute COVID-19 infection and related symptoms tend to resolve 4 weeks post-infection. However, for some patients, new, recurrent, or persisting symptoms remain beyond the acute phase and persist for months, post-infection. The symptoms that remain have been referred to as long-COVID. A number of research sites employed 129 Xe magnetic resonance imaging (MRI) during the pandemic and evaluated patients post-infection, months after hospitalization or home-based care as a way to better understand the consequences of infection on 129 Xe MR gas-exchange and ventilation imaging.

A systematic review and comprehensive search were employed using MEDLINE via PubMed (April 2023) using the National Library of Medicine’s Medical Subject Headings and key words: post-COVID-19, MRI, 129 Xe, long-COVID, COVID pneumonia, and post-acute COVID-19 syndrome. Fifteen peer-reviewed manuscripts were identified including four editorials, a single letter to the editor, one review article, and nine original research manuscripts (2020–2023). MRI and MR spectroscopy results are summarized from these prospective, controlled studies, which involved small sample sizes ranging from 9 to 76 participants.

Key findings included: 1)129 Xe MRI gas-exchange and ventilation abnormalities, 3 months post-COVID-19 infection, and 2) a combination of MRI gas-exchange and ventilation abnormalities alongside persistent symptoms in patients hospitalized and not hospitalized for COVID-19, 1-year post-infection. The persistence of respiratory symptoms and 129 Xe MRI abnormalities in the context of normal or nearly normal pulmonary function test results and chest computed tomography (CT) was consistent. Longitudinal improvements were observed in long-term follow-up of long-COVID patients but mean 129 Xe gas-exchange, ventilation heterogeneity values and symptoms remained abnormal, 1-year post-infection.

Pulmonary functional MRI using inhaled hyperpolarized 129 Xe gas has played a role in detecting gas-exchange and ventilation abnormalities providing complementary information that may help develop our understanding of the root causes of long-COVID.

Link | PDF (Journal of Magnetic Resonance Imaging)

 

[SNT Gatchaman]

the knowledge gap remains large. Regardless of the symptoms, etiology, and mechanisms, it has been very difficult to find the root cause of long-COVID in most patients because there is a wide range of different body system symptoms involved.

Given the fact that pulmonary function tests (PFT) including the diffusing capacity of the lung for carbon monoxide (DLCO ) is often normal or mildly abnormal in people reporting symptoms consistent with long-COVID, it was hypothesized that sensitive novel pulmonary functional MR imaging methods such as inhaled hyperpolarized gas might reveal causal or at least correlative pathologies.

 

[SNT Gatchaman]

Injected paramagnetic contrast methods mainly rely on changes in blood-tissue perfusion and endothelial changes that may be detected by contrast-induced changes in relaxation, as in the case of conventional 1H MRI. Instead, 129Xe MRI directly and simultaneously measure inhaled (and not injected) xenon atoms in the airspaces, alveolar tissue, and red blood cells.

MRI physics porn —

The detection of 129Xe signal in MRI is challenging, due to the much lower concentration of gas xenon atoms (as compared to tissue 1H) and the four times lower gyromagnetic ratio of 129Xe in comparison to 1H. Taken together these factors reduce the net magnetization available for 129Xe MRI. While the first factor may have limited solutions due to the fixed amount of gas that may be inhaled, increasing the fraction of spin-up atoms (or polarization) can be addressed through hyperpolarization, which may be accomplished using a laser-excited rubidium vapor to increase the “spin-up” xenon atom population beyond thermal equilibrium.

Like 1H atoms in a magnet, 129Xe experiences locally different magnetic environments in different tissues and states that result in chemical shift. [...] at least three distinct 129Xe spectroscopic resonance frequencies exist in equilibrium when 129Xe gas is inhaled in the lung. The gas signal is arbitrarily set at 0 ppm, with the alveolar membrane tissue peak residing at 197 ppm, and the combination of the blood plasma and red blood cell (RBC) signals shifted to approximately 218–222 ppm.

By using a radio-frequency (RF) pulse with sufficient spectral selectivity in the frequency domain, all 129Xe compartments may be excited and images generated simultaneously and with a single, inhaled 129Xe gas dose.

 

[SNT Gatchaman]

Together, these abnormal MRI and CT findings generate testable hypotheses about the role of the alveolar tissue barrier and pulmonary vascular compartments in long-COVID. [...] it is possible that micro-embolic or micro-thrombotic obstruction of small capillaries explains these results. Alternatively, vascular injury, vascular remodeling, or shunt may also be possible

Certainly, post-mortem micro-CT imaging provided evidence of abnormal alveolar-level structures and occluded capillaries. Pulmonary vascular abnormalities observed may also stem from vascular remodeling or persistent micro-emboli which would agree with histological evidence of severe endothelial damage and distorted, elongated vessels alongside micro-emboli and shunt.

 

[Sean]

Interesting paper.

using a laser-excited rubidium vapor to increase the “spin-up” xenon atom population beyond thermal equilibrium.

I love it when science talks dirty.

Stimulated emission of coherent light, phase state, quantum effects, thermodynamics...

 

[SNT Gatchaman]

Combining Hyperpolarized 129Xe MR Imaging and Spectroscopy to Non-Invasively Estimate Pulmonary Vascular Resistance (2025)
Anna Costelle; Junlan Lu; Suphachart Leewiwatwong; Berend E. Westerhof; David Mummy; Sudarshan Rajagopal; Bastiaan Driehuys

Hyperpolarized 129Xe MRI/MRS enables quantitative mapping of function in lung airspaces, membrane tissue, and red blood cells (RBCs) within the pulmonary capillaries. The RBC signal also exhibits cardiogenic oscillations that are reduced in pre-capillary pulmonary hypertension (PH). This effect is obscured in patients with concomitant defects in transfer from airspaces to RBCs, which increase RBC oscillation amplitudes.

Here, we provide a framework for interpreting RBC oscillations and show their relationship to pulsatile blood flow, capillary blood volume, capillary compliance, and impedance of the capillary and venous circulation. This framework was first applied to characterize RBC oscillations in a cohort of subjects with pulmonary disease but no known PH (n=129).

129Xe MRI of RBC transfer was used to estimate capillary blood volume, and as it decreased, RBC oscillations sharply increased (r2adj=0.53), consistent with model predictions. Model-derived fit parameters were then used to estimate the distribution of pulmonary vascular resistance (PVR) across arterial, capillary, and venous circulation, and to correct oscillations for RBC transfer defects. 70% of PVR was estimated to arise from pulmonary arteries, 11% from capillaries, and 19% from veins. When tested in a second cohort of subjects who underwent 129Xe MRI/MRS and right heart catheterization (n=40), oscillations corrected for capillary blood volume correlated moderately with PVR (r2=0.27, p=0.0014). For every 1.96 WU increase in PVR, corrected oscillations decreased by 1 absolute percentage point.

This work demonstrates that, although 129Xe-RBC oscillations are only indirectly sensitive to pre-capillary obstruction, corrected oscillations below 7.5% were 100% specific for elevated PVR.

Link | PDF (Journal of Applied Physiology) [Open Access]