Anthropomorphic radiotherapy phantoms require tissue-equivalent materials to achieve Hounsfield units (HU) that are comparable to those of human tissue. Traditional manufacturing methods are limited by their high-cost and incompatibility with patient-specific customization. Additive manufacture (AM) provides a significant opportunity to enable manufacture of patient-specific geometries at relatively low cost. However, AM technologies are currently limited in terms of available material types, and consequently enable very little variation in achievable HU when standard manufacturing parameters are used. This work demonstrates a novel method whereby the partial volume effect (PVE) is utilized to control the HU of an AM material, in particular, enabling low HU in the range typical of lung tissue. The method enables repeatable design of lung HU and is compatible with commercial machines using standard print parameters. A custom algorithm demonstrates the clinical application of the method, whereby patient-specific computed tomography (CT) data are algorithmically calibrated according to AM print parameters and confirmed to be robust as a custom anthropomorphic radiotherapy phantoms.

The use of slaughterhouse-based hearts has advantages over hearts obtained from laboratory animals for preclinical testing. However, slaughterhouse hearts have greater variability in cardiac function; this has resulted in a dispute over their actual reproducibility. This study explores the feasibility of examining the cardioplegic effluent during hypothermic cardiac arrest for the presence of biomarkers to predict poststorage heart function of slaughterhouse hearts. This may enable proactive measures to optimize preservation strategies and improve the initial cardiac performance of slaughterhouse heart experiments. Slaughterhouse pig hearts (n = 9; 420 ± 30 g) were arrested and flushed with an additional liter cardioplegia after 1 h. Effluent samples were examined for ammonia, lactate, troponin, and inorganic phosphate. After 2 h, hearts were hemoreperfused in the ex vivo heart platform PhysioHeart™ to restore physiological cardiac functions and to identify correlations between biomarkers and cardiac output. There was a negative correlation between cardiac output of revived hearts and levels of ammonia (r = −0.865; p = 0.002) and lactate (r = −0.763; p = 0.01). No correlation was found between cardiac output and levels of phosphate (r = −0.553; p = 0.12) and troponin (r = −0.367; p = 0.331). The analysis approach to assess cardioplegic biomarkers was feasible and enabled the estimation of the effectiveness of organ protection and cardiac function before reperfusion. Ammonia is a predictor for cardiac dysfunction. Effluent analysis prior to heart revival can uncover poststorage cardiac dysfunction in isolated hearts and may prevent failed experiments while improving reproducibility and standardization.

Airway transmural pressure in healthy homogeneous lungs with dilated airways is approximately equal to the difference between intraluminal and pleural pressure. However, bronchoconstriction causes airway narrowing, parenchymal distortion, dynamic hyperinflation, and the emergence of ventilation defects (VDefs) affecting transmural pressure. This study aimed to investigate the changes in transmural pressure caused by bronchoconstriction in a bronchial tree. Transmural pressures before and during bronchoconstriction were estimated using an integrative computational model of bronchoconstriction. Briefly, this model incorporates a 12-generation symmetric bronchial tree, and the Anafi and Wilson model for the individual airways of the tree. Bronchoconstriction lead to the emergence of VDefs and a relative increase in peak transmural pressures of up to 84% compared to baseline. The highest increase in peak transmural pressure occurred in a central airway outside of VDefs, and the lowest increase was 27% in an airway within VDefs illustrating the heterogeneity in peak transmural pressures within a bronchial tree. Mechanisms contributing to the increase in peak transmural pressures include increased regional ventilation and dynamic hyperinflation both leading to increased alveolar pressures compared to baseline. Pressure differences between intraluminal and alveolar pressure increased driven by the increased airway resistance and its contribution to total transmural pressure reached up to 24%. In conclusion, peak transmural pressure in lungs with VDefs during bronchoconstriction can be substantially increased compared to dilated airways in healthy homogeneous lungs and is highly heterogeneous. Further insights will depend on the experimental studies taking these conditions into account.

The deep inspiration (DI) maneuver entices a great deal of interest because of its ability to temporarily ease the flow of air into the lungs. This salutary effect of a DI is proposed to be mediated, at least partially, by momentarily increasing the operating length of airway smooth muscle (ASM). Concerningly, this premise is largely derived from a growing body of in vitro studies investigating the effect of stretching ASM by different magnitudes on its contractility. The relevance of these in vitro findings remains uncertain, as the real range of strains ASM undergoes in vivo during a DI is somewhat elusive. In order to understand the regulation of ASM contractility by a DI and to infer on its putative contribution to the bronchodilator effect of a DI, it is imperative that in vitro studies incorporate levels of strains that are physiologically relevant. This review summarizes the methods that may be used in vivo in humans to estimate the strain experienced by ASM during a DI from functional residual capacity (FRC) to total lung capacity (TLC). The strengths and limitations of each method, as well as the potential confounders, are also discussed. A rough estimated range of ASM strains is provided for the purpose of guiding future in vitro studies that aim at quantifying the regulatory effect of DI on ASM contractility. However, it is emphasized that, owing to the many limitations and confounders, more studies will be needed to reach conclusive statements.

An inverse model consisting of two elastic compartments connected in series and served by two airway conduits has recently been fit to measurements of respiratory impedance in obese subjects. Increases in the resistance of the distal conduit of the model with increasing body mass index have been linked to peripheral airway compression by mass loading of the chest wall. Nevertheless, how the two compartments and conduits of this simple model map onto the vastly more complicated structure of an actual lung remain unclear. To investigate this issue, we developed a multiscale branching airway tree model of the respiratory system that predicts realistic input impedance spectra between 5 and 20 Hz with only four free parameters. We use this model to study how the finite elastances of the conducting airway tree and the proximal upper airways affect impedance between 5 and 20 Hz. We show that progressive constriction of the peripheral airways causes impedance to appear to arise from two compartments connected in series, with the proximal compartment being a reflection of the elastance of upper airway structures proximal to the tracheal entrance and the lower compartment reflecting the pulmonary airways and tissues. We thus conclude that while this simple inverse model allows evaluation of overall respiratory system impedance between 5 and 20 Hz in the presence of upper airway shunting, it does not allow the separate contributions of central versus peripheral pulmonary airways to be resolved.

Volatile anesthetics have been shown to reduce lung resistance through dilation of constricted airways. In this study, we hypothesized that diffusion of inhaled anesthetics from airway lumen to smooth muscle would yield significant bronchodilation in vivo, and systemic recirculation would not be necessary to reduce lung resistance (R L ) and elastance (E L ) during sustained bronchoconstriction. To test this hypothesis, we designed a delivery system for precise timing of inhaled volatile anesthetics during the course of a positive pressure breath. We compared changes in R L , E L , and anatomic dead space (V D ) in canines (N = 5) during pharmacologically induced bronchoconstriction with intravenous methacholine, and following treatments with: (1) targeted anesthetic delivery to V D and (2) continuous anesthetic delivery throughout inspiration. Both sevoflurane and isoflurane were used during each delivery regimen. Compared to continuous delivery, targeted delivery resulted in significantly lower doses of delivered anesthetic and decreased end-expiratory concentrations. However, we did not detect significant reductions in R L or E L for either anesthetic delivery regimen. This lack of response may have resulted from an insufficient dose of the anesthetic to cause bronchodilation, or from the preferential distribution of air flow with inhaled anesthetic delivery to less constricted, unobstructed regions of the lung, thereby enhancing airway heterogeneity and increasing apparent R L and E L .

A couple of fused deposition modeling (FDM) three-dimensional (3D) printers using variable infill density patterns were employed to simulate human muscle, fat, and lung tissue as it is represented by Hounsfield units (HUs) in computer tomography (CT) scans. Eleven different commercial plastic filaments were assessed by measuring their mean HU on CT images of small cubes printed with different patterns. The HU values were proportional to the mean effective density of the cubes. Polylactic acid (PLA) filaments were chosen. They had good printing characteristics and acceptable HU. Such filaments obtained from two different vendors were then tested by printing two sets of cubes comprising 10 and 6 cubes with 100% to 20% and 100% to 50% infill densities, respectively. They were printed with different printing patterns named “Regular” and “Bricks,” respectively. It was found that the HU values measured on the CT images of the 3D-printed cubes were proportional to the infill density with slight differences between vendors and printers. The Regular pattern with infill densities of about 30%, 90%, and 100% were found to produce HUs equivalent to lung, fat, and muscle. This was confirmed with histograms of the respective region of interest (ROI). The assessment of popular 3D-printing materials resulted in the choice of PLA, which together with the proposed technique was found suitable for the adequate simulation of the muscle, fat, and lung HU in printed patient-specific phantoms.