Bioimpedance-Based Assessment of Acute Lung Injury

Introduction:: The inhalation of harmful substances can cause substantial damage to the pulmonary epithelium, potentially leading to lung dysfunction [1]. For instance, the aspiration of large amounts of gastric acid triggers inflammation in the lung epithelial cells, ultimately resulting in acute respiratory distress syndrome (ARDS) and pneumonia [2]. ARDS is characterized by severe airway and lung parenchyma injury, with a high mortality rate (40–70%) even with access to intensive care [3]. Therefore, early and precise diagnosis of acid-induced injury, as a risk factor for the development of ARDS, is critical to provide effective treatments.

Measuring the electrical impedance of lung tissue has great potential to be a non-invasive and accurate diagnostic tool for certain lung diseases and injuries [1]. In the clinical setting, electrical impedance tomography (EIT) is frequently used to continuously monitor lung ventilation and perfusion, alveoli recruitment or derecruitment, and alveoli overdistension [4]. In this study, we explore the potential of bioimpedance measurements in characterizing gastric aspiration-induced lung injury. The results collectively suggest that electrical bioimpedance can be used as an efficient and accurate diagnosis tool for acid-induced lung injury.


Materials and Methods:: Lungs were isolated from Sprague-Dawley rats (SAS SD Rats; Charles River Laboratories; body weight: 200-250 g). All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at Stevens Institute of Technology. Briefly, animals were euthanized, and lungs were isolated and rinsed with 1´PBS prior to the bioimpedance measurements. Then, rat lungs were connected to a small animal ventilator (PhysioSuite, Kent Scientific) through the endotracheal cannula and ventilated with a tidal volume of 7 mL/kg at a rate of 70 breaths per minute (bpm). To induce injury in the lungs caused by acid, different volumes (1, 3, and 5 mL) of hydrochloric acid (HCl) solution (0.1 N, pH level: 1.5) were intratracheally instilled into the lung via a 10 mL syringe connected to the trachea cannula. After each HCL instillation, 0.5 ml of air was injected through tubing to ensure that HCl had reached the distal parts of the lungs.

The impedance values were measured with the four-probe method with alternate current (AC) using an LCR meter (Keysight Technologies). The impedance analyzer was set to apply a sinusoidal current of 100 mA as the electrical excitation for all the measurements. The frequency sweep measurements were done in the frequency range from 100 Hz to 300 kHz, and resistance (R, real part of impedance) and reactance (X, imaginary part of impedance) were collected. The impedance (Z) values were calculated based on the measured resistance and reactance via Z = R + jX.


Results, Conclusions, and Discussions:: To assess the functionality of the bioimpedance measurement setup, we first evaluated the electrical impedance of the rat lungs ex vivo with different peak inspiratory pressures (PIP: 0, 5, and 15 cmH₂O) (Figs. 1A-1D). An alternating electrical current (AC) with various frequencies (range: 100 Hz–300 kHz) and a maximum amplitude of 100 μA were injected into lung tissue using two current-carrying electrodes (CC1 and CC2), while two voltage pickup electrodes (PU1 and PU2) measured the voltage at the measurement site (Figs. 1A, 1B). The frequency-sweep curves showed the same pattern for electrical impedance with the change in frequency (Fig. 1C). Moreover, the impedance was increased with increasing the lung’s internal pressure due to stretching of the lung tissue and narrowing of the electron/ion conductive pathways with increasing PIP (Figs. 1C, 1D).

We further investigated whether the electrical impedance of the lung could be altered by creating an acid-induced lung injury model in the lungs (Figs. 1E-1H). Intratracheal instillation of HCL solution (concentration: 0.1N), a commonly used solution to model gastric aspiration-induced lung injury, was achieved to create the pathological condition (Figs. 1E, 1F) [5]. The results indicated that HCL-induced injury led to a decrease in the electrical impedance of the lung (Fig. 1G). The reduction of electrical impedance in injured lungs was connected to the replacement of air with liquid in air space and an increase in the alveolar septa thickness due to tissue dissociation, which collectively provide more conductive pathways for electron/ion mobility. Notably, histological images of the injured lungs (5 mL HCL) confirmed excessive accumulation of liquid and debris in the alveolar airspace and increased thickness of the alveolar septa (Fig. 1H).



Overall, the bioimpedance assessment of lung tissue can be used as a diagnostic tool for minimally invasive detection and quantification of pathological lung tissue, such as acid-induced lung injury.


Acknowledgements (Optional): : NSF Career Award (No. 2143620)

References (Optional): : 1. Chen et al., “Opto-electromechanical quantification of epithelial barrier function in injured and healthy airway tissues.”, APL bioengineering, 7(1), p.016104, (2023).

2. Beitler, et al., “Preventing ARDS: progress, promise, and pitfalls.”. Chest, 146(4), pp.1102-1113, (2014).

3. Nagase et al., “Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A₂”, Nature Immunology, Volume 1, No 1, (2000).

4. Tomicic et al., "Lung monitoring with electrical impedance tomography: technical considerations and clinical applications." Journal of thoracic disease, vol. 11, No. 7 (2019).

5. Matute-Bello et al., “Animal models of acute lung injury.”, Am J Physiol Lung Cell Mol Physiol 295: L379–L399, (2008).