Three broad classifications of acute respiratory failure etiologies based on regional ventilation and perfusion by electrical impedance tomography: a hypothesis-generating study

Background The aim of this study was to validate whether regional ventilation and perfusion data measured by electrical impedance tomography (EIT) with saline bolus could discriminate three broad acute respiratory failure (ARF) etiologies. Methods Perfusion image was generated from EIT-based impedance–time curves caused by 10 ml 10% NaCl injection during a respiratory hold. Ventilation image was captured before the breath holding period under regular mechanical ventilation. DeadSpace%, Shunt% and VQMatch% were calculated based on lung perfusion and ventilation images. Ventilation and perfusion maps were divided into four cross-quadrants (lower left and right, upper left and right). Regional distribution defects of each quadrant were scored as 0 (distribution% ≥ 15%), 1 (15% > distribution% ≥ 10%) and 2 (distribution% < 10%). Data percentile distributions in the control group and clinical simplicity were taken into consideration when defining the scores. Overall defect scores (DefectV, DefectQ and DefectV+Q) were the sum of four cross-quadrants of the corresponding images. Results A total of 108 ICU patients were prospectively included: 93 with ARF and 15 without as a control. PaO2/FiO2 was significantly correlated with VQMatch% (r = 0.324, P = 0.001). Three broad etiologies of ARF were identified based on clinical judgment: pulmonary embolism-related disease (PED, n = 14); diffuse lung involvement disease (DLD, n = 21) and focal lung involvement disease (FLD, n = 58). The PED group had a significantly higher DeadSpace% [40(24)% vs. 14(15)%, PED group vs. the rest of the subjects; median(interquartile range); P < 0.0001] and DefectQ score than the other groups [1(1) vs. 0(1), PED vs. the rest; P < 0.0001]. The DLD group had a significantly lower DefectV+Q score than the PED and FLD groups [0(1) vs. 2.5(2) vs. 3(3), DLD vs. PED vs. FLD; P < 0.0001]. The FLD group had a significantly higher DefectV score than the other groups [2(2) vs. 0(1), FLD vs. the rest; P < 0.0001]. The area under the receiver operating characteristic (AUC) for using DeadSpace% to identify PED was 0.894 in all ARF patients. The AUC for using the DefectV+Q score to identify DLD was 0.893. The AUC for using the DefectV score to identify FLD was 0.832. Conclusions Our study showed that it was feasible to characterize three broad etiologies of ARF with EIT-based regional ventilation and perfusion. Further study is required to validate clinical applicability of this method. Trial registration clinicaltrials, NCT04081142. Registered 9 September 2019—retrospectively registered, https://clinicaltrials.gov/show/NCT04081142.

Measurement of Electrical Impedance Tomography-Based Regional Ventilation Delay for Individualized Titration of End-Expiratory Pressure

Rationale: Individualized positive end-expiratory pressure (PEEP) titration might be beneficial in preventing tidal recruitment. To detect tidal recruitment by electrical impedance tomography (EIT), the time disparity between the regional ventilation curves (regional ventilation delay inhomogeneity [RVDI]) can be measured during controlled mechanical ventilation when applying a slow inflation of 12 mL/kg of body weight (BW). However, repeated large slow inflations may result in high end-inspiratory pressure (PEI), which might limit the clinical applicability of this method. We hypothesized that PEEP levels that minimize tidal recruitment can also be derived from EIT-based RVDI through the use of reduced slow inflation volumes. Methods: Decremental PEEP trials were performed in 15 lung-injured pigs. The PEEP level that minimized tidal recruitment was estimated from EIT-based RVDI measurement during slow inflations of 12, 9, 7.5, or 6 mL/kg BW. We compared RVDI and PEI values resulting from different slow inflation volumes and estimated individualized PEEP levels. Results: RVDI values from slow inflations of 12 and 9 mL/kg BW showed excellent linear correlation (R2 = 0.87, p < 0.001). Correlations decreased for RVDI values from inflations of 7.5 (R2 = 0.68, p < 0.001) and 6 (R2 = 0.42, p < 0.001) mL/kg BW. Individualized PEEP levels estimated from 12 and 9 mL/kg BW were comparable (bias −0.3 cm H2O ± 1.2 cm H2O). Bias and scatter increased with further reduction in slow inflation volumes (for 7.5 mL/kg BW, bias 0 ± 3.2 cm H2O; for 6 mL/kg BW, bias 1.2 ± 4.0 cm H2O). PEI resulting from 9 mL/kg BW inflations were comparable with PEI during regular tidal volumes. Conclusions: PEEP titration to minimize tidal recruitment can be individualized according to EIT-based measurement of the time disparity of regional ventilation courses during slow inflations with low inflation volumes. This sufficiently decreases PEI and may reduce potential clinical risks.

The effect of combination inhaled therapy on ventilation distribution measured by SPECT/CT imaging in uncontrolled asthma

Background: Asthma is characterised by heterogeneous ventilation as measured by 3-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting beta agonist (ICS/LABA) treatment response is variable in asthma and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma. Methods: Twenty‐two symptomatic asthmatic participants underwent Single-Photon Emission Computed Tomography (SPECT)/CT imaging with Technegas, before and after 8-week fluticasone/formoterol (1000/40µg/day) treatment. Lung regions that were non-ventilated, low-ventilated or well-ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airway function (Sacin and Scond, respectively). Forced Oscillation Technique (FOT) was used to measure respiratory system resistance and reactance. Results: At baseline and post treatment Scond z-score was related to % non-ventilated lung, while Sacin z-score was related to % low-ventilated lung. Although symptoms, spirometry, FOT and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide-range of change in SPECT ventilation such that greater % non-ventilated lung, older age, and higher Scond, predicted a reduction in non-ventilated lung after treatment. Discussion: SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable with improvement occurring when small airway dysfunction and ventilation defects are more severe. Persistent ventilation defects which correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodelling underlie these defects.

Quantification of dual-energy CT-derived functional parameters as potential imaging markers for progression of idiopathic pulmonary fibrosis

Objectives The individual course of disease in idiopathic pulmonary fibrosis (IPF) is highly variable. Assessment of disease activity and prospective estimation of disease progression might have the potential to improve therapy management and indicate the onset of treatment at an earlier stage. The aim of this study was to evaluate whether regional ventilation, lung perfusion, and late enhancement can serve as early imaging markers for disease progression in patients with IPF. Methods In this retrospective study, contrast-enhanced dual-energy CT scans of 32 patients in inspiration and delayed expiration were performed at two time points with a mean interval of 15.4 months. The pulmonary blood volume (PBV) images obtained in the arterial and delayed perfusion phase served as a surrogate for arterial lung perfusion and parenchymal late enhancement. The virtual non-contrast (VNC) images in inspiration and expiration were non-linearly registered to provide regional ventilation images. Image-derived parameters were correlated with longitudinal changes of lung function (FVC%, DLCO%), mean lung density in CT, and CT-derived lung volume. Results Regional ventilation and late enhancement at baseline preceded future change in lung volume (R - 0.474, p 0.006/R - 0.422, p 0.016, respectively) and mean lung density (R - 0.469, p 0.007/R - 0.402, p 0.022, respectively). Regional ventilation also correlated with a future change in FVC% (R - 0.398, p 0.024). Conclusion CT-derived functional parameters of regional ventilation and parenchymal late enhancement are potential early imaging markers for idiopathic pulmonary fibrosis progression. Key Points • Functional CT parameters at baseline (regional ventilation and late enhancement) correlate with future structural changes of the lung as measured with loss of lung volume and increase in lung density in serial CT scans of patients with idiopathic pulmonary fibrosis. • Functional CT parameter measurements in high-attenuation areas (- 600 to - 250 HU) are significantly different from normal-attenuation areas (- 950 to - 600 HU) of the lung. • Mean regional ventilation in functional CT correlates with a future change in forced vital capacity (FVC) in pulmonary function tests.