Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is an imaging methodology that uses blood as an endogenous contrast agent to quantify flow. One limitation of this method of capillary blood quantification when applied in the lung is the contribution of signals from non-capillary blood. Intensity thresholding is one approach that has been proposed for minimizing the non-capillary blood signal. This method has been tested in previous in silico modeling studies; however, it has only been tested under a restricted set of physiological conditions (supine posture and a cardiac output of 5 L/min). This study presents an in silico approach that extends previous intensity thresholding analysis to estimate the optimal "per-slice" intensity threshold value using the individual components of the simulated ASL signal (signal arising independently from capillary blood as well as pulmonary arterial and pulmonary venous blood). The aim of this study was to assess whether the threshold value should vary with slice location, posture, or cardiac output. We applied an in silico modeling approach to predict the blood flow distribution and the corresponding ASL quantification of pulmonary perfusion in multiple sagittal imaging slices. There was a significant increase in ASL signal and heterogeneity (COV = 0.90 to COV = 1.65) of ASL signals when slice location changed from lateral to medial. Heterogeneity of the ASL signal within a slice was significantly lower (P = 0.03) in prone (COV = 1.08) compared to in the supine posture (COV = 1.17). Increasing stroke volume resulted in an increase in ASL signal and conversely an increase in heart rate resulted in a decrease in ASL signal. However, when cardiac output was increased via an increase in both stroke volume and heart rate, ASL signal remained relatively constant. Despite these differences, we conclude that a threshold value of 35% provides optimal removal of large vessel signal independent of slice location, posture, and cardiac output.

The recent COVID-19 pandemic has propelled the field of aerosol science to the forefront, particularly the central role of virus-laden respiratory droplets and aerosols. The pandemic has also highlighted the critical need, and value for, an information bridge between epidemiological models (that inform policymakers to develop public health responses) and within-host models (that inform the public and health care providers how individuals develop respiratory infections). Here, we review existing data and models of generation of respiratory droplets and aerosols, their exhalation and inhalation, and the fate of infectious droplet transport and deposition throughout the respiratory tract. We then articulate how aerosol transport modeling can serve as a bridge between and guide calibration of within-host and epidemiological models, forming a comprehensive tool to formulate and test hypotheses about respiratory tract exposure and infection within and between individuals.

Specific ventilation imaging (SVI) proposes that using oxygen-enhanced 1H MRI to capture signal change as subjects alternatively breathe room air and 100% O2 provides an estimate of specific ventilation distribution in the lung. How well this technique measures SV and the effect of currently adopted approaches of the technique on resulting SV measurement is open for further exploration. We investigated (1) How well does imaging a single sagittal lung slice represent whole lung SV? (2) What is the influence of pulmonary venous blood on the measured MRI signal and resultant SVI measure? and (3) How does inclusion of misaligned images affect SVI measurement? In this study, we utilized two patient-based in silico models of ventilation, perfusion, and gas exchange to address these questions for normal healthy lungs. Simulation results from the two healthy young subjects show that imaging a single slice is generally representative of whole lung SV distribution, with a calculated SV gradient within 90% of that calculated for whole lung distributions. Contribution of O2 from the venous circulation results in overestimation of SV at a regional level where major pulmonary veins cross the imaging plane, resulting in a 10% increase in SV gradient for the imaging slice. A worst-case scenario simulation of image misalignment increased the SV gradient by 11.4% for the imaged slice.

Multiple thoracic imaging modalities have been developed to link structure to function in the diagnosis and monitoring of lung disease. Volumetric computed tomography (CT) renders three-dimensional maps of lung structures and may be combined with positron emission tomography (PET) to obtain dynamic physiological data. Magnetic resonance imaging (MRI) using ultrashort-echo time (UTE) sequences has improved signal detection from lung parenchyma; contrast agents are used to deduce airway function, ventilation-perfusion-diffusion, and mechanics. Proton MRI can measure regional ventilation-perfusion ratio. Quantitative imaging (QI)-derived endpoints have been developed to identify structure-function phenotypes, including air-blood-tissue volume partition, bronchovascular remodeling, emphysema, fibrosis, and textural patterns indicating architectural alteration. Coregistered landmarks on paired images obtained at different lung volumes are used to infer airway caliber, air trapping, gas and blood transport, compliance, and deformation. This document summarizes fundamental good practice stereological principles in QI study design and analysis; evaluates technical capabilities and limitations of common imaging modalities; and assesses major QI endpoints regarding underlying assumptions and limitations, ability to detect and stratify heterogeneous, overlapping pathophysiology, and monitor disease progression and therapeutic response, correlated with and complementary to, functional indices. The goal is to promote unbiased quantification and interpretation of in vivo imaging data, compare metrics obtained using different QI modalities to ensure accurate and reproducible metric derivation, and avoid misrepresentation of inferred physiological processes. The role of imaging-based computational modeling in advancing these goals is emphasized. Fundamental principles outlined herein are critical for all forms of QI irrespective of acquisition modality or disease entity.