Multiple-breath Washout 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis Lung Disease
Bibliographic record
Abstract
Hyperpolarized 129Xe magnetic resonance imaging (Xe-MRI) enables the direct visualization of lung ventilation and is sensitive to regional ventilation abnormalities in diseases such as cystic fibrosis (CF). While single-breath Xe-MRI yields high-resolution images of ventilation after a single breath hold and quantifies disease burden using the ventilation defect percent (VDP), it provides only a static snapshot of gas distribution. Multiple-breath washout (MBW) Xe-MRI offers a dynamic alternative by following the washout of 129Xe gas after multiple breaths resulting in the fractional ventilation (FV), a measure of gas clearance per breath. Furthermore, the spatial heterogeneity of FV (CoVFV) can also be assessed. This thesis focuses on further developing MBW Xe-MRI towards meaningful clinical implementation in pediatric CF through three axes: repeatability, responsiveness to treatment, and development of multiple-slice MBW Xe-MRI. First, the repeatability of MBW Xe-MRI was assessed in healthy children and those with stable CF. FV and CoVFV were found to be highly repeatable in both cohorts, though repeatability was lower in CF likely due to inherent disease instability. Furthermore, CoVFV moderately correlated with pulmonary function tests (PFTs) as well as the ventilation defect percent (VDP). Second, MBW Xe-MRI was evaluated longitudinally in a pediatric CF cohort undergoing elexacaftor/tezacaftor/ivacaftor (ETI) therapy for 24 months. FV and CoVFV reflected improvements attributed to ETI therapy over 1 month and were consistent with improvements in PFTs and VDP. Furthermore, CoVFV provided complementary information for longitudinal treatment monitoring by capturing increasing ventilation heterogeneity even when VDP and PFTs remained stable. Lastly, to address technical limitations, a multi-slice MBW Xe-MRI acquisition was developed and demonstrated in pediatric CF. This approach was determined to be feasible, provided improved spatial resolution and coverage in the slice direction, and allowed for the calculation of the FV gravitational gradient. Overall, this work advances MBW Xe-MRI from proof-of-concept toward clinical applicability. With further technical refinements, MBW Xe-MRI may complement existing modalities by providing physiologically meaningful, regional ventilation metrics for assessing lung disease and treatment response in children with CF and other lung diseases.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".