Biology subjects

Burrowes, K.

Publications and source records attributed to Burrowes, K..

3 recordsLinked to original sources

bioRxiv2026

Reported estimates of human airway dimensions are inconsistent across studies

RationaleRespiratory diseases are a source of immense socioeconomic burden globally. In silico approaches can predict changes in human lung function due to disease or response to therapy. By stratifying patient-specific response a priori, these models can enable clinical-scale deployment of precision medicine strategies. Key to this is developing accurate organ geometries on which the models can be simulated. However, we lack analyses assessing the clinical applicability of reported airway dimension estimates. ObjectiveTo investigate physiologically-/anatomically-relevant airway dimension estimates and evaluate consistency across reported literature. MethodsWe conducted a systematic review of 37 published datasets. Airway wall thickness estimates were mined for healthy subjects and patients, and standardised to the Horsfield order airway generations. We simulated dynamic lung function to quantitatively assess their physiological relevance. We created an online database to make all datasets available to the research community. Measurements and Main ResultsReported human airway wall thickness estimates are inconsistent across studies. K-means clustering divided estimates for healthy subjects and patients into three and four clusters, respectively. Only one of the clusters in each category yielded anatomically-relevant estimates. Pressure-volume curves generated to assess physiological relevance also showed that only one cluster in each category exhibited plausible physiology. Principal Component Analysis weakly implicated imaging modalities to explain this inconsistency. ConclusionsReported airway dimension estimates are inconsistent and lack standardisation. To support future modelling efforts, we report physiologically-relevant estimates and introduce an open-access airway-dimension database to help standardise geometric inputs and quantify how measurement variability propagates to functional predictions.

biophysics↗

bioRxiv2025

Regional and Global Analysis of Cerebrovascular Reactivity Using 4D Flow MRI

Cerebrovascular reactivity (CVR) assessments are promising for diagnostic and prognostic applications related to vascular function and neurodegenerative diseases. Current vascular imaging-based CVR indices have been limited to single-vessel analysis and report conflicting results, for example, whether there are differences in CVR between sexes. Alternative vascular imaging-based indices can be derived from 4D flow MRI, namely intracranial pulse wave velocity and pulsatility transmission, which are based on vascular regions and offer a more comprehensive perspective on vascular function that can also scale to a global level. To date, these types of indices have not been measured with a vascular stimulus. In this work, standard single-vessel and novel regional and global CVR indices were studied in 10 healthy young adults (29 {+/-} 2 years, 5 male, 5 female) in response to hypercapnia. Consistent increases in flow, area and velocity manifested at all levels and were greater in males. Regional pulse wave velocity and pulsatility transmission offered a minimum 40% increase in the dynamic range of CVR magnitudes that may benefit cohort stratification. Notably, pulse wave velocity increased in 50% of the vascular regions (most probably due to vasoconstriction), accompanying an increase in flow; a profound observation given the common expectation of vasorelaxation with hypercapnia. Consistently reduced flow, velocity, area, pulse wave velocity, and transmission index reactivities in females may partially explain the varying pathological outcomes between sexes, evidencing the continued value of 4D flow for the evaluation of CVR in other cohorts. New and NoteworthyCerebrovascular reactivity (CVR) of 4D flow-based intracranial pulse wave velocity and pulsatility transmission were evaluated during hypercapnia for the first time. Remarkably, pulse wave velocity increased in some cases and decreased in others, suggesting that vasorelaxation may not always occur during hypercapnia. These indices also expanded CVR dynamic range by more than 40 % compared to common velocimetry techniques, which could offer improved cohort stratification. Evidence of diminished CVR in females was also observed.

bioengineering↗

bioRxiv2022

De novo discovery of traits co-occurring with chronic obstructive pulmonary disease

Epidemiological research indicates that chronic obstructive pulmonary disease (COPD) is a heterogeneous group of chronic lung conditions that are typically accompanied by cardiovascular disease, depression, lung cancer and other conditions. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with COPD and the co-occuring conditions, suggesting common biological mechanisms underlying COPD and these co-occuring conditions. To identify them, we have integrated information across different biological levels (i.e. genetic variants, lung-specific 3D genome structure, gene expression and protein-protein interactions) to build lung-specific gene regulatory and protein-protein interaction networks. We have queried these networks using disease-associated SNPs for COPD, unipolar depression and coronary artery disease. Our results show that COPD-associated SNPs can control genes involved in the regulation of lung or pulmonary function, asthma, brain region volumes, cortical surface area, depressed affect, neuroticism, Parkinsons disease, white matter microstructure and smoking behaviour. We describe the regulatory connections, genes and biochemical pathways that underly these co-occuring trait-SNP-gene associations. Collectively, our findings provide new avenues for the investigation of the underlying biology and diverse clinical presentations of COPD. In so doing, we identify a collection of genetic variants and genes that may aid COPD patient stratification and treatment.

genomics↗