Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation.

BACKGROUND: Lung volume measurements are important for monitoring functional aeration and recruitment, and may help guide adjustments in ventilator settings. The expiratory phase of APRV may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (TExp). We hypothesized that expiratory flow rate would correlate with estimated lung volume (ELV), as measured using a modified nitrogen washout/washin technique in a large animal lung injury model. METHODS: Eight pigs (35.2±1.0kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration (TLow), which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15mmHg in normal and Tween-injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC InView Tool. The expiratory flow-time slope and TExp were measured from the expiratory flow profile. RESULTS: Lung elastance increased with Tween-induced lung injury from 29.3±7.3cmH2O/L to 39.9±15.1cmH2O/L and chest wall elastance increased with increasing intra-abdominal pressures from 15.3±4.1cmH2O/L to 25.7±10.0cmH2O/L in the normal lung and 15.8±6.0cmH2O/L to 33.0±6.2cmH2O/L in the Tween-injured lung (p=0.39). ELV decreased from 1.90±0.83L in the Tween-Injured lung to 0.67±0.1L by increasing intra-abdominal pressures to 15mmHg. This had a significant correlation with a TExp decrease from 2.3±0.8s to 1.0±0.1s in the Tween-injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29±0.06L/s2 to 0.63±0.05L/s2 (ρ = 0.78). CONCLUSIONS: Changes in ELV over time, and the TExp and flow-time slope, can be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.

Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient's lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.

Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry.

Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS. The immediate goal of mechanical ventilation in ARDS should be to prevent atelectrauma resulting from repetitive alveolar collapse and reopening. However, a long-term goal should be to re-open collapsed and edematous regions of the lung and reduce regions of high mechanical stress that lead to regional volutrauma. In this paper, we consider the proposed strategy used by the full-term newborn to open the fluid-filled lung during the initial breaths of life, by ratcheting tissues opened over a series of initial breaths with brief expirations. The newborn's cry after birth shares key similarities with the Airway Pressure Release Ventilation (APRV) modality, in which the expiratory duration is sufficiently short to minimize end-expiratory derecruitment. Using a simple computational model of the injured lung, we demonstrate that APRV can slowly open even the most recalcitrant alveoli with extended periods of high inspiratory pressure, while reducing alveolar re-collapse with brief expirations. These processes together comprise a ratchet mechanism by which the lung is progressively recruited, similar to the manner in which the newborn lung is aerated during a series of cries, albeit over longer time scales.

Sustained vs. Intratidal Recruitment in the Injured Lung During Airway Pressure Release Ventilation: A Computational Modeling Perspective.

INTRODUCTION: During mechanical ventilation, cyclic recruitment and derecruitment (R/D) of alveoli result in focal points of heterogeneous stress throughout the lung. In the acutely injured lung, the rates at which alveoli can be recruited or derecruited may also be altered, requiring longer times at higher pressure levels to be recruited during inspiration, but shorter times at lower pressure levels to minimize collapse during exhalation. In this study, we used a computational model to simulate the effects of airway pressure release ventilation (APRV) on acinar recruitment, with varying inspiratory pressure levels and durations of exhalation. MATERIALS AND METHODS: The computational model consisted of a ventilator pressure source, a distensible breathing circuit, an endotracheal tube, and a porcine lung consisting of recruited and derecruited zones, as well as a transitional zone capable of intratidal R/D. Lung injury was simulated by modifying each acinus with an inflation-dependent surface tension. APRV was simulated for an inhalation duration (Thigh) of 4.0 seconds, inspiratory pressures (Phigh) of 28 and 40 cmH2O, and exhalation durations (Tlow) ranging from 0.2 to 1.5 seconds. RESULTS: Both sustained acinar recruitment and intratidal R/D within the subtree were consistently higher for Phigh of 40 cmH2O vs. 28 cmH2O, regardless of Tlow. Increasing Tlow was associated with decreasing sustained acinar recruitment, but increasing intratidal R/D, within the subtree. Increasing Tlow was associated with decreasing elastance of both the total respiratory system and transitional subtree of the model. CONCLUSIONS: Our computational model demonstrates the confounding effects of cyclic R/D, sustained recruitment, and parenchymal strain stiffening on estimates of total lung elastance during APRV. Increasing inspiratory pressures leads to not only more sustained recruitment of unstable acini but also more intratidal R/D. Our model indicates that higher inspiratory pressures should be used in conjunction with shorter exhalation times, to avoid increasing intratidal R/D.

First Stabilize and then Gradually Recruit: A Paradigm Shift in Protective Mechanical Ventilation for Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed "baby lung"); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a "protective lung approach" (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an "open lung approach" (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a "stabilize lung approach" (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4-6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy.

Positron Emission Tomography-Computed Tomography Imaging of Selective Lobar Delivery of Stem Cells in Ex Vivo Lung Model of Mechanical Ventilation.

Introduction: The delivery of cell therapies may be an important frontier to treat different respiratory diseases in the near future. However, the cell size, delivery conditions, cell viability, and effect in the pulmonary function are critical factors. We performed a proof-of-concept experiment using ex vivo lungs and novel subglottic airway device that allows for selective lobar isolation and administration of drugs and biologics in liquid solution deep into the lung tissues, while simultaneously ventilating the rest of the lung lobes. Methods: We used radiolabeled cells and positron emission tomography-computed tomography (PET-CT) imaging to demonstrate the feasibility of high-yield cell delivery to a specifically targeted lobe. This study proposes an alternative delivery method of live cells labeled with radioactive isotope into the lung parenchyma and tracks the cell delivery using PET-CT imaging. The technique combines selective lobar isolation and lobar infusion to carry large particles distal to the trachea, subtending bronchial segments and reaching alveoli in targeted regions. Results: The solution with cells and carrier achieved a complete and homogeneous lobar distribution. An increase in tissue density was shown on the computed tomography (CT) scan, and the PET-CT imaging demonstrated retention of the activity at central, peripheral lung parenchyma, and pleural surface. The increase in CT density and metabolic activity of the isotope was restricted to the desired lobe only without leak to other lobes. Conclusion: The selective lobe delivery is targeted and imaging-guided by bronchoscopy and CT to a specific diseased lobe during mechanical ventilation. The feasibility of high-yield cell delivery demonstrated in this study will lead to the development of potential novel therapies that contribute to lung health.

Pulmonary Blood Volume Among Older Adults in the Community: The MESA Lung Study.

BACKGROUND: The pulmonary vasculature is essential for gas exchange and impacts both pulmonary and cardiac function. However, it is difficult to assess and its characteristics in the general population are unknown. We measured pulmonary blood volume (PBV) noninvasively using contrast enhanced, dual-energy computed tomography to evaluate its relationship to age and symptoms among older adults in the community. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) is an ongoing community-based, multicenter cohort. All participants attending the most recent MESA exam were selected for contrast enhanced dual-energy computed tomography except those with estimated glomerular filtration rate <60 mL/min per 1.73 m2. PBV was calculated by material decomposition of dual-energy computed tomography images. Multivariable models included age, sex, race/ethnicity, education, height, weight, smoking status, pack-years, and scanner model. RESULTS: The mean age of the 727 participants was 71 (range 59-94) years, and 55% were male. The race/ethnicity distribution was 41% White, 29% Black, 17% Hispanic, and 13% Asian. The mean±SD PBV in the youngest age quintile was 547±180 versus 433±194 mL in the oldest quintile (P<0.001), with an approximately linear decrement of 50 mL per 10 years of age ([95% CI, 32-67]; P<0.001). Findings were similar with multivariable adjustment. Lower PBV was associated independently with a greater dyspnea after a 6-minute walk (P=0.04) and greater composite dyspnea symptom scores (P=0.02). Greater PBV was also associated with greater height, weight, lung volume, Hispanic race/ethnicity, and nonsmoking history. CONCLUSIONS: Pulmonary blood volume was substantially lower with advanced age and was associated independently with greater symptoms scores in the elderly.

Unshrinking the baby lung to calm the VILI vortex.

A hallmark of ARDS is progressive shrinking of the 'baby lung,' now referred to as the ventilator-induced lung injury (VILI) 'vortex.' Reducing the risk of the VILI vortex is the goal of current ventilation strategies; unfortunately, this goal has not been achieved nor has mortality been reduced. However, the temporal aspects of a mechanical breath have not been considered. A brief expiration prevents alveolar collapse, and an extended inspiration can recruit the atelectatic lung over hours. Time-controlled adaptive ventilation (TCAV) is a novel ventilator approach to achieve these goals, since it considers many of the temporal aspects of dynamic lung mechanics.

Assessment of Heterogeneity in Lung Structure and Function During Mechanical Ventilation: A Review of Methodologies.

The mammalian lung is characterized by heterogeneity in both its structure and function, by incorporating an asymmetric branching airway tree optimized for maintenance of efficient ventilation, perfusion, and gas exchange. Despite potential benefits of naturally occurring heterogeneity in the lungs, there may also be detrimental effects arising from pathologic processes, which may result in deficiencies in gas transport and exchange. Regardless of etiology, pathologic heterogeneity results in the maldistribution of regional ventilation and perfusion, impairments in gas exchange, and increased work of breathing. In extreme situations, heterogeneity may result in respiratory failure, necessitating support with a mechanical ventilator. This review will present a summary of measurement techniques for assessing and quantifying heterogeneity in respiratory system structure and function during mechanical ventilation. These methods have been grouped according to four broad categories: (1) inverse modeling of heterogeneous mechanical function; (2) capnography and washout techniques to measure heterogeneity of gas transport; (3) measurements of heterogeneous deformation on the surface of the lung; and finally (4) imaging techniques used to observe spatially-distributed ventilation or regional deformation. Each technique varies with regard to spatial and temporal resolution, degrees of invasiveness, risks posed to patients, as well as suitability for clinical implementation. Nonetheless, each technique provides a unique perspective on the manifestations and consequences of mechanical heterogeneity in the diseased lung.

Clinical significance and applications of oscillometry.

Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.

A comparison of endotracheal tube compensation techniques for the measurement of respiratory mechanical impedance at low frequencies.

Measurement of respiratory impedance ([Formula: see text]) in intubated patients requires accurate compensation for pressure losses across the endotracheal tube (ETT). In this study, we compared time-domain (TD), frequency-domain (FD) and combined time-/frequency-domain (FT) methods for ETT compensation. We measured total impedance ([Formula: see text]) of a test lung in series with three different ETT sizes, as well as in three intubated porcine subjects. Pressure measurement at the distal end of the ETT was used to determine the true [Formula: see text]. For TD compensation, pressure distal to the ETT was obtained based on its resistive and inertial properties, and the corresponding [Formula: see text] was estimated. For FD compensation, impedance of the isolated ETT was obtained from oscillatory flow and pressure waveforms, and then subtracted from [Formula: see text]. For TF compensation, the nonlinear resistive properties of the ETT were subtracted from the proximal pressure measurement, from which the linear resistive and inertial ETT properties were removed in the frequency-domain to obtain [Formula: see text]. The relative root mean square error between the actual and estimated [Formula: see text] ([Formula: see text]) showed that TD compensation yielded the least accurate estimates of [Formula: see text] for the in vitro experiments, with small deviations observed at higher frequencies. The FD and TF compensations yielded estimates of [Formula: see text] with similar accuracies. For the porcine subjects, no significant differences were observed in [Formula: see text] across compensation methods. FD and TF compensation of the ETT may allow for accurate oscillometric estimates of [Formula: see text] in intubated subjects, while avoiding the difficulties associated with direct tracheal pressure measurement.

Effects of Lung Injury on Regional Aeration and Expiratory Time Constants: Insights From Four-Dimensional Computed Tomography Image Registration.

Rationale: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration. Methods: Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes. Results: Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants. Conclusion: Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.

Case Studies in Physiology: Temporal variations of the lung parenchyma and vasculature in asymptomatic COVID-19 pneumonia: a multispectral CT assessment.

This study reports systematic longitudinal pathophysiology of lung parenchymal and vascular effects of asymptomatic COVID-19 pneumonia in a young, healthy never-smoking male. Inspiratory and expiratory noncontrast along with contrast dual-energy computed tomography (DECT) scans of the chest were performed at baseline on the day of acute COVID-19 diagnosis (day 0), and across a 90-day period. Despite normal vital signs and pulmonary function tests on the day of diagnosis, the CT scans and corresponding quantification metrics detected abnormalities in parenchymal expansion based on image registration, ground-glass (GGO) texture (inflammation) as well as DECT-derived pulmonary blood volume (PBV). Follow-up scans on day 30 showed improvement in the lung parenchymal mechanics as well as reduced GGO and improved PBV distribution. Improvements in lung PBV continued until day 90. However, the heterogeneity of parenchymal mechanics and texture-derived GGO increased on days 60 and 90. We highlight that even asymptomatic COVID-19 infection with unremarkable vital signs and pulmonary function tests can have measurable effects on lung parenchymal mechanics and vascular pathophysiology, which may follow apparently different clinical courses. For this asymptomatic subject, post COVID-19 regional mechanics demonstrated persistent increased heterogeneity concomitant with return of elevated GGOs, despite early improvements in vascular derangement.NEW & NOTEWORTHY We characterized the temporal changes of lung parenchyma and microvascular pathophysiology from COVID-19 infection in an asymptomatic young, healthy nonsmoking male using dual-energy CT. Lung parenchymal mechanics and microvascular disease followed different clinical courses. Heterogeneous perfused blood volume became more uniform on follow-up visits up to 90 days. However, post COVID-19 mechanical heterogeneity of the lung parenchyma increased after apparent improvements in vascular abnormalities, even with normal spirometric indices.

Regional Gas Transport During Conventional and Oscillatory Ventilation Assessed by Xenon-Enhanced Computed Tomography.

Enhanced intrapulmonary gas transport enables oscillatory ventilation modalities to support gas exchange using extremely low tidal volumes at high frequencies. However, it is unknown whether gas transport rates can be improved by combining multiple frequencies of oscillation simultaneously. The goal of this study was to investigate distributed gas transport in vivo during multi-frequency oscillatory ventilation (MFOV) as compared with conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). We hypothesized that MFOV would result in more uniform rates of gas transport compared to HFOV, measured using contrast-enhanced CT imaging during wash-in of xenon gas. In 13 pigs, xenon wash-in equilibration rates were comparable between CMV and MFOV, but 21 to 39% slower for HFOV. By contrast, the root-mean-square delivered volume was lowest for MFOV, increased by 70% during HFOV and 365% during CMV. Overall gas transport heterogeneity was similar across all modalities, but gravitational gradients and regional patchiness of specific ventilation contributed to regional ventilation heterogeneity, depending on ventilator modality. We conclude that MFOV combines benefits of low lung stretch, similar to HFOV, but with fast rates of gas transport, similar to CMV.

Oscillatory ventilation redux: alternative perspectives on ventilator-induced lung injury in the acute respiratory distress syndrome.

For patients with the acute respiratory distress syndrome (ARDS), ventilation strategies that limit end-expiratory derecruitment and end-inspiratory overdistension are the only interventions to have significantly reduced the morbidity and mortality. For this reason, the use of high-frequency oscillatory ventilation (HFOV) was considered to be an ideal protective strategy, given its reliance on very low tidal volumes cycled at very high rates. However, results from clinical trials in adults with ARDS have demonstrated that HFOV does not improve clinical outcomes. Recent experimental and computational studies have shown that oscillation of a mechanically heterogeneous lung with multiple simultaneous frequencies can reduce parenchymal strain, improve gas exchange, and maintain lung recruitment at lower distending pressures compared to traditional 'single-frequency' HFOV. This review will discuss the theoretical rationale for the use of multiple oscillatory frequencies in ARDS, as well as the mechanisms by which it may reduce the risk for ventilator-induced lung injury.

Quantitative CT imaging and advanced visualization methods: potential application in novel coronavirus disease 2019 (COVID-19) pneumonia.

Increasingly, quantitative lung computed tomography (qCT)-derived metrics are providing novel insights into chronic inflammatory lung diseases, including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and more. Metrics related to parenchymal, airway, and vascular anatomy together with various measures associated with lung function including regional parenchymal mechanics, air trapping associated with functional small airways disease, and dual-energy derived measures of perfused blood volume are offering the ability to characterize disease phenotypes associated with the chronic inflammatory pulmonary diseases. With the emergence of COVID-19, together with its widely varying degrees of severity, its rapid progression in some cases, and the potential for lengthy post-COVID-19 morbidity, there is a new role in applying well-established qCT-based metrics. Based on the utility of qCT tools in other lung diseases, previously validated supervised classical machine learning methods, and emerging unsupervised machine learning and deep-learning approaches, we are now able to provide desperately needed insight into the acute and the chronic phases of this inflammatory lung disease. The potential areas in which qCT imaging can be beneficial include improved accuracy of diagnosis, identification of clinically distinct phenotypes, improvement of disease prognosis, stratification of care, and early objective evaluation of intervention response. There is also a potential role for qCT in evaluating an increasing population of post-COVID-19 lung parenchymal changes such as fibrosis. In this work, we discuss the basis of various lung qCT methods, using case-examples to highlight their potential application as a tool for the exploration and characterization of COVID-19, and offer scanning protocols to serve as templates for imaging the lung such that these established qCT analyses have the best chance at yielding the much needed new insights.

CT image segmentation for inflamed and fibrotic lungs using a multi-resolution convolutional neural network.

The purpose of this study was to develop a fully-automated segmentation algorithm, robust to various density enhancing lung abnormalities, to facilitate rapid quantitative analysis of computed tomography images. A polymorphic training approach is proposed, in which both specifically labeled left and right lungs of humans with COPD, and nonspecifically labeled lungs of animals with acute lung injury, were incorporated into training a single neural network. The resulting network is intended for predicting left and right lung regions in humans with or without diffuse opacification and consolidation. Performance of the proposed lung segmentation algorithm was extensively evaluated on CT scans of subjects with COPD, confirmed COVID-19, lung cancer, and IPF, despite no labeled training data of the latter three diseases. Lobar segmentations were obtained using the left and right lung segmentation as input to the LobeNet algorithm. Regional lobar analysis was performed using hierarchical clustering to identify radiographic subtypes of COVID-19. The proposed lung segmentation algorithm was quantitatively evaluated using semi-automated and manually-corrected segmentations in 87 COVID-19 CT images, achieving an average symmetric surface distance of [Formula: see text] mm and Dice coefficient of [Formula: see text]. Hierarchical clustering identified four radiographical phenotypes of COVID-19 based on lobar fractions of consolidated and poorly aerated tissue. Lower left and lower right lobes were consistently more afflicted with poor aeration and consolidation. However, the most severe cases demonstrated involvement of all lobes. The polymorphic training approach was able to accurately segment COVID-19 cases with diffuse consolidation without requiring COVID-19 cases for training.

CT Image Segmentation for Inflamed and Fibrotic Lungs Using a Multi-Resolution Convolutional Neural Network.

The purpose of this study was to develop a fully-automated segmentation algorithm, robust to various density enhancing lung abnormalities, to facilitate rapid quantitative analysis of computed tomography images. A polymorphic training approach is proposed, in which both specifically labeled left and right lungs of humans with COPD, and nonspecifically labeled lungs of animals with acute lung injury, were incorporated into training a single neural network. The resulting network is intended for predicting left and right lung regions in humans with or without diffuse opacification and consolidation. Performance of the proposed lung segmentation algorithm was extensively evaluated on CT scans of subjects with COPD, confirmed COVID-19, lung cancer, and IPF, despite no labeled training data of the latter three diseases. Lobar segmentations were obtained using the left and right lung segmentation as input to the LobeNet algorithm. Regional lobar analysis was performed using hierarchical clustering to identify radiographic subtypes of COVID-19. The proposed lung segmentation algorithm was quantitatively evaluated using semi-automated and manually-corrected segmentations in 87 COVID-19 CT images, achieving an average symmetric surface distance of $0.495 \pm 0.309$ mm and Dice coefficient of $0.985 \pm 0.011$. Hierarchical clustering identified four radiographical phenotypes of COVID-19 based on lobar fractions of consolidated and poorly aerated tissue. Lower left and lower right lobes were consistently more afflicted with poor aeration and consolidation. However, the most severe cases demonstrated involvement of all lobes. The polymorphic training approach was able to accurately segment COVID-19 cases with diffuse consolidation without requiring COVID-19 cases for training.