Phase-resolved Functional Lung MRI Reveals Distinct Lung Perfusion Phenotype in Children and Adolescents with [LC], 2025, Pöhler+

Phase-resolved Functional Lung MRI Reveals Distinct Lung Perfusion Phenotype in Children and Adolescents with Post–COVID-19 Condition
Gesa H. Pöhler; Andreas Voskrebenzev; Marc-Luca Heinze; Valentina Skeries; Filip Klimeš; Julian Glandorf; Jan Eckstein; Nigar Babazade; Marius Wernz; Alexander Pfeil; Gesine Hansen; Frank K. Wacker; Jens Vogel-Claussen; Martin Wetzke; Diane Miriam Renz

BACKGROUND
Although measurable organic dysfunctions are frequently absent in pediatric patients with post–COVID-19 condition (PCC), this condition adversely affects quality of life. Free-breathing phase-resolved functional lung (PREFUL) MRI may be useful for assessing lung function in pediatric patients with PCC.

PURPOSE
To detect lung changes in children and adolescents with PCC compared with healthy control participants using PREFUL MRI.

MATERIALS AND METHODS
In this single-center, prospective, cross-sectional study conducted between April 2022 and April 2023, children and adolescents (age ≤17 years) with PCC and age-and sex-matched healthy participants underwent MRI. Subgroup analysis was performed in participants with PCC who had cardiopulmonary symptoms. Regional ventilation, flow-volume loop correlation metric (FVL-CM), quantified perfusion, ventilation and perfusion defect percentages, and ventilation-perfusion ratios were compared between participants with PCC and controls using the Wilcoxon signed rank test. Correlation of imaging parameters with spirometry, heart rate, respiratory rate, and Bell score (fatigue severity) in participants with PCC was assessed using the Spearman rank correlation coefficient.

RESULTS
The final study sample included 54 participants (27 participants with PCC and 27 matched control participants; median age, 15 years [IQR, 11–17 years]; 14 male participants). Twenty-one participants had cardiopulmonary symptoms. Participants with PCC had lower regional ventilation (median, 0.2 mL/mL [IQR, 0.1–0.2 mL/mL] vs 0.2 mL/mL [IQR, 0.2–0.2 mL/mL]; P = .047) and quantified perfusion (49 mL/min per 100 mL [IQR, 33–60 mL/min per 100 mL] vs 78 mL/min per 100 mL [IQR, 59–89 mL/min per 100 mL]; P < .001). Participants with PCC and cardiopulmonary symptoms had lower FVL-CMs (median, 0.99 arbitrary units [au] [IQR, 0.98–0.99 au] vs 0.99 au [IQR, 0.990.99 au]; P = .01) and higher ventilation defect (median, 7.6% [IQR, 4.5%–15.1%] vs 5.4% [IQR, 2.7%–7.1%]; P = .047) and perfusion defect percentage (median, 3.2% [IQR, 2.4%–4.2%] vs 2.3% [IQR, 1.8%–3.5%]; P = .02) compared with matched control participants. In participants with PCC, greater lung perfusion correlated with increased chronic fatigue severity (ρ = 0.48; P = .009) and higher ventilation-perfusion mismatch correlated with increased heart rate (ρ = 0.44; P = .02).

CONCLUSION
Free-breathing phase-resolved functional lung MRI–derived parameters helped identify a distinct phenotype of lung perfusion in children and adolescents with PCC and were correlated with heart rate and chronic fatigue severity.

Link | PDF (Radiology) [Open Access]

 

Do we know anything about the clinical significance of the findings? And are there any reasons to believe that the differences are noticeable?

It would be good to have something to distinguish LC-patients by, although it seems like an elaborate test?

 

These are 12-17 yos, well matched with controls. 100% of the cohort had fatigue, nearly 60% had concentration difficulties, just over a third insomnia, a third dizziness and just under a third headache. They don't specifically evaluate for PEM or test OI.

It's a notable set of findings in a 27+27 study. Major difference in pulmonary microcirculation demonstrated, despite normal standard lung function tests. There is a dose-response relationship with Bell disability and also with resting HR*.

See also the xenon-mri tag.

A picture's worth a thousand words, here are the money shots —



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*I don't want to derail the thread, but even with significant pathophysiology demonstrated by advanced MRI, they can't avoid one instance of:

Spoiler

The elevated heart and respiratory rates in participants with PCC, although remaining within normal ranges, may indicate compensatory mechanisms for subclinical diastolic impairments or reflect psychologic factors, such as anxiety or stress related to the PCC diagnosis.

 

I wish they could have just stuck to the topic and not speculated about the mental state of children.. That’s all I’m going to say.

I hope we might learn something from the rest of their work!

 

I'll email clinical colleagues and see if I can interest anyone in putting a young cohort together. But first I'd need to know that the technique was doable. Looking quickly at methods, it would likely require the sort of software upgrades which wouldn't be on the clinical scanners; they may be more accessible on the research machines, though that's not a given.

I wouldn't have thought so. For HR the increase was 87 (70–100) vs 79 (69–84) — case vs control. Which is in the physiologically normal range.

RR is given as breaths/sec. 0.3 (0.3–0.4) vs 0.3 (0.2–0.3). p = 0.02. At 1 sig fig that translates to an RR range /minute as 18-24 vs 12-18.

PREFUL is a new technique (feasibility and validation studies 2017-20 onward) so we'd have to look at the some earlier reports in CF, COPD and chronic pulmonary thromboembolic disease.

They reference —

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung PREFUL MRI in healthy volunteers and COPD, CTEPH, and CF patients (2018, Magnetic Resonance in Medicine)

Repeatability of Phase-Resolved Functional Lung PREFUL-MRI Ventilation and Perfusion Parameters in Healthy Subjects and COPD Patients (2021, Journal of Magnetic Resonance Imaging)

PREFUL MRI for Monitoring Perfusion and Ventilation Changes after Elexacaftor-Tezacaftor-Ivacaftor Therapy for Cystic Fibrosis: A Feasibility Study (2024, Radiology: Cardiothoracic Imaging)

 

https://www.eurekalert.org/news-releases/1074080

News Release 25-Feb-2025
Lung abnormalities seen in children and teens with long COVID
Peer-Reviewed Publication

Radiological Society of North America



image:

Images show exemplary coronal sections of phase-resolved functional lung MRI ventilation and perfusion maps in a 15-year-old female participant with post–COVID-19 condition (PCC) and in a sex- and age-matched healthy control participant. (A, B) Images show regional ventilation, with values of (A) 0.1 mL/mL in the participant with PCC and (B) 0.5 mL/mL in the healthy control participant. Regarding dynamic ventilation (C, D), images show the flow-volume loop correlation metric, with (C) the participant with PCC at 0.98 arbitrary units (au) and (D) the healthy control participant at 0.99 au. (E, F) Images show perfusion maps depicting a median quantified perfusion of 27 mL/min per 100 mL for the participant with PCC and 89 mL/min per 100 mL for the healthy control participant.

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Credit: Radiological Society of North America (RSNA)

OAK BROOK, Ill. – An advanced type of MRI uncovers significant lung abnormalities in children and adolescents with long COVID, according to a new study published today in Radiology, a journal of the Radiological Society of North America (RSNA).

Post-COVID-19 condition, commonly known as long COVID, can affect individuals of all ages and is diagnosed when symptoms persist for more than 12 weeks after an initial COVID-19 infection. Children and adolescents typically experience a milder form of the condition, but common symptoms such as chronic fatigue, headaches and poor concentration can negatively impact school performance and social activities.

While chest CT is frequently used to diagnose and monitor lung function of adults with long COVID, it is not typically recommended in children because it exposes the patient to ionizing radiation and may require injection of a contrast agent.

Young patients with suspected long COVID are typically evaluated with pulmonary function tests, echocardiography and reviews of medical history. Unfortunately, conventional pulmonary tests often show normal lung and cardiac function, even in symptomatic patients.

“Parents should understand that their children’s persistent symptoms after COVID-19 may have a measurable physiological basis, even when standard medical tests appear normal,” said lead study author Gesa H. Pöhler, M.D., a senior physician in the Department of Diagnostic and Interventional Radiology at Hannover Medical School in Germany.

The researchers employed phase-resolved functional lung (PREFUL) MRI. This advanced MRI technology can analyze lung ventilation (air movement in and out of the lungs) and perfusion (blood flow through the lungs). PREFUL MRI doesn’t require the use of radiation or intravenous contrast agents and can be done while the patient breathes freely, making it a suitable procedure for children.

“Our research provides the first comprehensive evidence of measurable regional lung perfusion abnormalities in pediatric post-COVID-19 condition using radiation-free, contrast-free lung imaging,” Dr. Pöhler said.

For the prospective study, conducted between April 2022 and 2023, the researchers enrolled 54 patients ranging in age from 11 to 17 years. Half of the patients were diagnosed with long COVID, and the other half were healthy controls. A self-reported assessment called the bell score was used to assess symptom severity in patients with long COVID.

Compared to healthy controls, children and adolescents with long COVID had significantly reduced blood flow in the lungs. A reduction in blood flow patterns in organs or other areas of the body can result in a lack of sufficient oxygen and nutrients.

The most prevalent symptom of fatigue affected all but one patient with long COVID.

“Importantly, the severity of fatigue symptoms correlated with these blood flow changes, suggesting a possible biological basis for the patients’ ongoing symptoms,” Dr. Pöhler said.

In addition to poor blood flow, a subgroup of long COVID patients with cardiopulmonary symptoms, such as shortness of breath, also showed a reduction of air movement and reach in the lungs.

The researchers suggest that continuous monitoring of lung abnormalities in children with long COVID at various stages of the condition could help guide therapeutic interventions and monitoring strategies.

“Quantitative lung MRI establishes a potential imaging biomarker profiling and helps to enable disease severity follow-up for this complex condition in the future,” Dr. Pöhler said.

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“Phase-resolved Functional Lung MRI Reveals Distinct Lung Perfusion Phenotype in Children and Adolescents with Post-COVID-19 Syndrome.” Collaborating with Dr. Pöhler were Andreas Voskrebenzev, Ph.D., Marc-Luca Heinze, Valentina Skeries, M.D., Filip Klimeš, Ph.D., Julian Glandorf, M.D., Jan Eckstein, M.D., Nigar Babazade, Marius Wernz, B.S., Alexander Pfeil, M.D., Gesine Hansen, M.D., Frank K. Wacker, M.D., Jens Vogel-Claussen, M.D., Martin Wetzke, M.D., and Diane Miriam Renz, M.D.

Radiology is edited by Linda Moy, M.D., New York University, New York, N.Y., and owned and published by the Radiological Society of North America, Inc. (https://pubs.rsna.org/journal/radiology)

RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org)

For patient-friendly information on chest MRI, visit RadiologyInfo.org.

Journal
Radiology

Subject of Research
People

Article Title
Phase-resolved Functional Lung MRI Reveals Distinct Lung Perfusion Phenotype in Children and Adolescents with Post-COVID-19 Syndrome

Article Publication Date
25-Feb-2025

 

God I hate that sentence. Feels very minimising when there are so many adolescents who have been bedridden for years with Post COVID.

 

Very interesting.

Don't think potential confounding can be ruled out - PCC patients had higher resting HR & respiratory rates than controls (87 vs 79bpm; RR ~0.3 vs 0.3b/s with PCC higher; p=.03 & .02) and ventilation metrics correlated with RR (rho up to -0.53, p<.02) so the mildly elevated RR may contribute to lower regional ventilation. They didn't control/adjust for RR/HR in the MRI analysis. The PCC group is also quite heterogeneous: ages 9-17, varied symptoms. The authors demonstrated a +ve correlation between quantified perfusion (rho=0.48, p=.009); it would have been interesting to know if the severity of other symptoms, e.g. dyspnoea, correlated with any assessed parameters. They also didn't attempt to correct for multiple comparisons (if a conservative correction like Bonferroni had been applied likely only a few values such as the perfusion diffs p<.001 would have probably remained significant).

Not at all familiar with the technique, so just a few open questions:

- Is the rapid sequence & post-processing sufficient to guard against motion artifacts?
- Presumably the observer dependence (segmentation validation) is fairly trivial?
- The perfusion values seem to depend on the calibration (ref 18) - is that reliable? Would it have been useful to compare PREFUL perfusion with another standard (e.g. perfusion scintigraphy?) in a subset of patients?
- The authors assume that the per-voxel signal changes are due solely to V/Q changes - would that still hold true if the patient's breathing pattern changed during the scan?

 

I've only skimmed, but I think this might be a mistake in the abstract:

And in the discussion:

But in the results section:

Which matches figure 6 where the lower the perfusion, the lower the Bell score.

Bell score is lower with more severe disability, so the abstract sentence seems to be saying the opposite of the sentence in the results section.

 

And I think there's another one: 14 males (vs 13/13 in Table 1).

The final study sample included 54 participants (27 participants with PCC and 27 matched control participants; median age, 15 years [IQR, 11–17 years]; 14 male participants).