Persistent 129Xe MRI Pulmonary and CT Vascular abnormalities in ... [PACS] , 2022, Parraga, Matheson (and related papers by Grist, Wild)

Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome

Alexander M. Matheson et al.

https://pubs.rsna.org/doi/10.1148/radiol.220492

Abstract

Background
In patients with post-acute COVID-19-syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other, or to symptoms and exercise limitation. The pathophysiological drivers of PACS in ever- and never-hospitalized patients are not well-understood.


Purpose
To determine the relationship of persistent symptoms and exercise limitation with 129Xe MRI and CT pulmonary vascular measurements in individuals with PACS.


Materials and Methods
In this prospective study, patients with PACS aged 18-80 years with a positive PCR COVID test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing-capacity-of-the-lung- for-carbon-monoxide (DLCO), 129Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 underwent spirometry, DLCO, and 129Xe MRI. The 129Xe MRI red-blood-cell (RBC) to alveolar-barrier signal ratio, RBC area-under-the-curve (AUC), CT volume-of-pulmonary-vessels with cross-sectional-area <5mm2 (BV5), and total-blood-volume (TBV) were quantified. St. George's Respiratory Questionnaire (SGRQ), International Physical Activity Questionnaire (IPAQ) and modified Borg Dyspnea Scale (mBDS) measured quality-of-life, exercise limitation and dyspnea. Differences between groups were compared using Welch's T-tests or Welch's ANOVA. Relationships were evaluated using Pearson (r) and Spearman (ρ) correlations.


Results
Forty participants were evaluated including six controls (mean age, 35±15 years[standard deviation], 3 women) and 34 participants with PACS (mean age, 53±13 years[SD], 18 women), of which 22 were never-hospitalized. The 129Xe MRI RBC:barrier ratio was lower in ever- hospitalized participants (P=.04) compared to controls. BV5 correlated with RBC AUC (ρ=.44,P=.03). The 129Xe MRI RBC:barrier ratio was related to DLCO (r=.57,P=.002) and FEV1 (ρ=.35,P=.03); RBC AUC was related to dyspnea (ρ=-.35,P=.04) and IPAQ score (ρ=.45,P=.02).


Conclusion
129Xe MRI measurements were lower in ever- hospitalized participants with post- acute COVID-19-syndrome, 34±25 weeks post-infection compared to controls. 129Xe MRI measures were associated with CT pulmonary vascular density, DLCO, exercise capacity, and dyspnea.

 

Yes, so there are four related papers.



Step on the 129Xe Gas: The MRI Race to Uncover Drivers of Post-COVID-19 Symptoms, 2022
Grace Parraga and Alexander M. Matheson
Editorial in the Radiology journal commenting on the Grist, Collier, Wild paper
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134267/



Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-Acute COVID-19 Syndrome
Alexander M. Matheson BSc1,2, Marrissa J. McIntosh BSc1,2, Harkiran K. Kooner BSc1,2, Justin Lee3, Vedanth Desaigoudar1,2, Elianna Bier MS4, Bastiaan Driehuys PhD4, Sarah Svenningsen PhD5, Giles E. Santyr PhD6,7, Miranda Kirby PhD8, Mitchell S. Albert PhD9-11, Yurii Shepelytskyi PhD9,10, Vira Grynko MSc9,10, Alexei Ouriadov PhD12, Mohamed Abdelrazek MD PhD13, Inderdeep Dhaliwal MD14, J. Michael Nicholson MD14 and Grace Parraga PhD

see Trish's post above for the abstract



Lung Abnormalities Depicted with Hyperpolarized Xenon MRI in Patients with Long COVID, 2022
James T. Grist, BSc PhD,1,,2,,3,,4 Guilhem J. Collier, PhD,5 Huw Walters, MBBS,1 Minsuok Kim, PhD,6 Mitchell Chen, BMBCh MEng DPhil FRCR,1 Gabriele Abu Eid, BSc,1 Aviana Laws,1Violet Matthews, BSc,1 Kenneth Jacob, BSc,1 Susan Cross, BSc,1 Alexandra Eves, BSc,1Marianne Durant, BSc,1 Anthony Mcintyre, BAppSci,1 Roger Thompson, PhD,7 Rolf F. Schulte, PhD,8 Betty Raman, MBBS DPhil,3 Peter A. Robbins, PhD,2 Jim M. Wild, PhD MSc MA,5Emily Fraser, PhD MBChB BSc,9 and Fergus Gleeson, MBBS1,,10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134268/

Abstract
Background
Post-Covid-19 condition describes symptoms following COVID-19 infection after four weeks. Symptoms are wide-ranging but breathlessness is common.

Purpose
The purpose of this study was to determine whether the previously described lung abnormalities on Hp-XeMRI in post-hospitalised COVID-19 participants are also present in non-hospitalised participants with Post-Covid-19 condition.

Methods
In this prospective study, non-hospitalised Post-Covid-19 condition (NHLC) and post-hospitalised COVID-19 (PHC) participants were enrolled from 06/2020 to 08/2021. Participants had chest CT, hyperpolarized pulmonary 129Xenon MRI (Hp-XeMRI), pulmonary function tests, 1-minute sit-to-stand test and breathlessness questionnaires. Control subjects underwent HP-XeMRI only. CT scans were analysed for post COVID interstitial lung disease severity using a previously published scoring system, and Full-scale Airway Network (FAN) modelling. Analysis used group and pair-wise comparisons between participants and controls, and correlations between participant clinical and imaging data.

Results
A total of 11 NHLC (4:7 Male: Female, 44 ± 11 years, [37-50], (mean ± SD, [95% CI]) and 12 PHC (10:2, Male: Female, 58 ± 10 years, [52-64]) participants were included, with a significant difference in age between groups, p = 0.05. NHLC participants were 287 ± 79, [240-334] and PHC 143 ± 72, [105-190] days from infection, respectively. NHLC and PHC participants had normal or near normal CT scans (0.3/25 ± 0.6, [0-0.63] and 7/25 ± 5, [4-10], respectively). Gas transfer (DLco (%)) was different between NHLC and PHC participants (76 ± 8%, [73-83] vs 86 ± 8%, [80-91] respectively, p = 0.04) but there was no evidence of other differences in lung function. Red Blood Cell:Tissue Plasma (RBC:TP) mean was different between volunteers vs PHC (0.45 ± 0.07, [0.43-0.47] vs (0.31 ± 0.10, [0.24-0.37], respectively, p = 0.02) and volunteers vs NHLC (0.37 ± 0.10, [0.31-0.44], p = 0.03) participants, but not between NHLC and PHC participants (p = 0.26). FAN results did not correlate with DLco or Hp- XeMRI.

Conclusion
NHLC and PHC subjects showed Hp-XeMRI RBC:TP abnormalities, with NHLC participants demonstrating lower DLco than PHC participants despite having normal CT scans.



129 Xe Pulmonary MRI for Individuals with Post-Acute COVID-19 Syndrome
Jim M Wild 1, Guilhem Collier 1
Online ahead of print here
Editorial commenting on the Matheson paper

 

People do seem excited about this. My notes based mainly on the Wild and Collier editorial:
This approach with radioactive Xenon gas (assessed in an MRI) is much more sensitive than the CT scans of lungs. It's possible to track the passage of the gas through the lungs, into the interstitial tissue and then taken up by the red blood cells. The method has been used in assessing post-Covid patients in China and in the UK.

Matheson et al found abnormalities in the uptake of the Xe gas into red blood cells in the post-Covid patients and linked it with 'evidence of small vessel pruning' from a CT assessment. So, the evidence points to a 'microvascular abnormality' i.e. the capillaries have been damaged. (I think we've seen evidence of this elsewhere in the body- there were images showing a disintegration of the capillary network, but I can't recall which paper.)

Wild and Collier make a few really good points. The Matheson et al study is small (34 patients, 6 controls). Also, there were big differences between the patient group and the control group (mean age of patients 53; mean age of controls 35).

Each participant inhaled the same amount of Xe gas, it wasn't calibrated to lung volume. So, that (and other possible variations) means that it is difficult to compare Xe concentrations. Also, lung function reduces with age. Wild and Collier quote one particular measure of lung function that has been shown to decline with age. Adjustments for that decline could wholly account for the difference found between the controls and patients, given the much younger age of the controls.

In summary, it's early. There needs to be more research done in bigger trials with better matched controls. The finding does however seem to fit with some of symptoms seen in Long Covid and ME/CFS.

From my brief skim of some of the reports, it's nice to see science functioning as it should, with various teams contributing knowledge, collaborating and offering useful critiques.

 

So, we don't have certain evidence of capillary damage here, but some indications of it.

The Berlin Cures/Hohberger people also found evidence of capillary damage in the retina of one man with Long Covid.
Neutralization of AAB Targeting G-Protein Coupled Receptors Improves Capillary Impairment and fatigue ... after COVID-19 Infection, 2021, Hohberger
They attributed that to autoantibodies and suggested they could fix it with BC007 - but even if those two things aren't true, the damage to microcirculation be.

I thought we had seen a paper with pictures of capillary damage, but I haven't been able to find it, so I'm probably just confused.