Assessment of ventilation heterogeneity and particle deposition in asthmatics using combined SPECT/CT imaging and computational modeling approaches
Bibliographic record
Abstract
PURPOSE: This study investigated asthma phenotypes and their associations with ventilation heterogeneity and particle deposition by utilizing Single-Photon Emission Computed Tomography (SPECT) imaging, quantitative Computed Tomography (qCT) imaging-based subgrouping, and a whole-lung computational model. MATERIALS AND METHODS: Two datasets were analyzed: one from a combined SPECT and CT (SPECT/CT) study with six asthmatic subjects, and another from the Severe Asthma Research Program (SARP) with 209 asthmatic subjects. Data from 35 previously acquired healthy subjects served as a control group. Each subject underwent CT scans at full inspiration and expiration, along with pulmonary function testing (PFT). The SPECT/CT study included ventilation SPECT imaging. Key qCT variables such as airway diameter, wall thickness, percentage of air trapping (AirT%), and percentage of small airway disease (fSAD%) were assessed. A subject-specific whole-lung computational fluid and particle dynamics (CFPD) model predicted airway resistance, particle deposition fraction, and the coefficient of variation (CV) for ventilation heterogeneity. Subjects were categorized into four predefined asthma imaging subgroups/clusters with increasing severity (C1-C4). CFPD-predicted CVs were validated against SPECT measurements. We compared PFT, qCT, and CFPD variables across SARP clusters and analyzed particle deposition fractions in large conducting, small conducting, and respiratory airways. RESULTS: Cluster C4 exhibited a significantly distinct ventilation profile compared to other clusters and health controls. This distinction contrasted with the insignificant differences between ventilation profiles in severity subgroups defined by conventional spirometry-based guidelines. Airway resistance varied significantly across the asthma clusters. Although both C3 and C4 clusters represented severe asthma, only C4 showed a significant increase in AirT%, primarily due to fSAD%. Since inflammatory phenotypes differ - C3 with wall thickening in large and small conducting airways, and C4 with elevated fSAD% and Emph% in small conducting and respiratory airways - fine particles (∼5 μm) and extrafine particles (∼1 μm) are more effective at reaching the respective regions in C3 and C4. Given that C2 and C4 have hyper-responsive phenotypes with narrowed conducting airways, fine particles are more effective in reaching these areas. Airway enlargement in targeted segments of the left lower lobe resulted in improved particle deposition. CONCLUSION: Our cluster-informed CFPD-based approach enhances the understanding of ventilation heterogeneity in asthma and holds potential for refining strategies for inhalational therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| 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 teacher head, 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".