Lung aeration in experimental malaria-associated acute respiratory distress syndrome by SPECT/CT analysis

Abstract

Malaria-associated acute respiratory distress syndrome (ARDS) is an inflammatory disease causing alveolar-pulmonary barrier lesion and increased vascular permeability characterized by severe hypoxemia. Computed tomography (CT), among other imaging techniques, allows the morphological and quantitative identification of lung lesions during ARDS. This study aims to identify the onset of malaria-associated ARDS development in an experimental model by imaging diagnosis. Our results demonstrated that ARDS-developing mice presented decreased gaseous exchange and pulmonary insufficiency, as shown by the SPECT/CT technique. The pulmonary aeration disturbance in ARDS-developing mice on the 5th day post infection was characterized by aerated tissues decrease and nonaerated tissue accumulation, demonstrating increased vascular permeability and pleural effusion. The SPECT/CT technique allowed the early diagnosis in the experimental model, as well as the identification of the pulmonary aeration. Notwithstanding, despite the fact that this study contributes to better understand lung lesions during malaria-associated ARDS, further imaging studies are needed.

Fig 1. Evaluation of survival, parasitemia and respiratory parameters during malaria-associated ARDS in experimental model.

(a) Survival curve, (b) parasitemia, (c) respiratory frequency, (d) enhanced pause (Penh), (e) tidal volume, (f) ventilation volume, (g) exhalation time and (h) inspiration time in Plasmodium berghei-infected DBA/2 mice on the 5^th and 7^th days post infection (dpi). The ARDS-developing mice died between 7^th and 12^th dpi, identified by gray band (a). Data presented as mean and standard error. Kruskal-Wallis Test, * p <0.01, ** p <0.001, ** p <0.0001, n = 7–12 mice/ experiment. Representative figures from 2–3 independent experiments NI: Non-Infected mice, ARDS: Acute Respiratory Distress Syndrome, HP: Hyperparasitemia.

Fig 2. Morphological evaluation during the development malaria-associated ARDS by computed tomography.

Representative topographic images of P. berghei ANKA-infected DBA/2 mice. The scale by Hounsfield Units 0 HU (Water Density) to -1,000 HU (Air Density). Representative figures from 2–4 independent experiments, n = 7–14 animals/experiment. NI: Non-Infected mice, ARDS: Acute Respiratory Distress Syndrome, HP: Hyperparasitemia; dpi: days post infection.

Fig 3. Malaria-associated ARDS decreases pulmonary aeration and promotes atelectasis as shown in computed tomography.

(a) Coronary posterior plane 3D pulmonary segmentation; Gray: Label CT, Yellow: Hyperexpanded, Red: Normally Aerated, Green: Poorly Aerated, Blue: Non-Aerated, Overlap: Merge. (b-e) Quantification of pulmonary aeration by computed tomography in DBA/2 mice after 5^th, 7^th, and 14^th days of Plasmodium berghei ANKA infection. (b) hyperexpanded aerated tissues; (c) Normally aerated tissues; (d) Poorly aerated tissues; (e) Non-aerated tissues; Representative images of 2 independent experiments, n = 8-12/experiment. Kruskal-Wallis. * p <0.05, ** p <0.01, ** p <0.001. NI: Non-Infected, ARDS: Acute respiratory distress syndrome, HP: Hyperparasitemia, dpi: days post infection.

Fig 4. Correlation between non-aerated lung tissue by computed tomography with respiratory parameters during malaria-associated ARDS.

(a) Strong negative correlation between decreased respiratory parameters with increased non-aerated CT tissue (p <0.005). (b) Moderate negative correlation between volume per minute of ventilation with increased non-aerated CT tissue. (c) Moderate negative correlation between tidal volume with the increase of non-aerated CT tissue (p <0.01. (d) Strong positive correlation between increased respiratory pause with the presence of non-aerated CT tissue (p <0.001). (e) Strong positive correlation between expiration time with increased non-aerated CT tissue (p <0.001). (f) Strong positive correlation between inspiratory time with increased non-aerated CT tissue (p <0.006). Data presented as mean ± SD. Correlation: Linear Regression (R2) test, n = 6 mice.

Fig 5. Malaria-associated ARDS promotes decreased ^99mTc-MAA activity during pulmonary perfusion.

(a) ARDS-developing mice presented absence of left lung perfusion in the coronal plane. (b) Reduced quantification of ^99mTc-MAA activity in the lungs of ARDS-developing mice. Data represented as mean ± SD. One Way ANOVA, ** p <0.01. Representative images of 2 isolated experiments, n = 7–10 mice/experiment. CPS/voxel: counts per second per voxel, NI: Noninfected mouse, ARDS: acute respiratory distress syndrome, HP: hyperpasitemia.