Radiological and Functional Assessment of Radiation-Induced Lung Injury in the Rat

Abstract

The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anesthetized and the right lung irradiated with a single dose of 18 Gy using 200-kVp x-rays. The lung function of the animals was measured every 2 weeks after irradiation with the breathing rate assay. CT scanning and radionuclide lung perfusion assay were performed prior to and 2, 4, 10, 16, and 34 weeks after irradiation. Significant elevation in breathing rate occurred after 16 weeks, with a maximal increase between 22 and 28 weeks. An increase in the right lung density started 4 weeks after irradiation. Regional measurements indicated a relatively uniform increase in density at 4 and 10 weeks, while foci of high-density areas were observed at the later time points. Changes in rat lung volume indicated shrinkage of the irradiated right lung and accompanying compensatory hypertrophy of the shielded left lung. Radionuclide perfusion assay showed significant decrease in relative blood flow in the irradiated right lung 4 weeks after hemithoracic irradiation. Changes in breathing rate provide an index of overall lung function while changes in lung density, volume, and perfusion are of particular importance for evaluating loco-regional differences in lung sensitivity. This study is the first demonstration that CT can be used to measure volume changes after thoracic irradiation in rats.

Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

“…After two training sessions, a BR at rest was recorded for each rat less than a week before the irradiation and then every 2 weeks till 38 weeks postirradiation. As described earlier (22,27), an unrestrained animal was placed in a 1,500-mL air-tight but transparent tube of a whole-body plethysmograph connected to a pressure transducer. The frequency of pressure changes inside the tube was recorded and displayed on a calibrated chart as breaths per minute (bpm).…”

Computed tomography of pulmonary sarcoid-like granulomas induced by complete Freund's adjuvant in rats

“…Less data are available concerning the use of lung CT in smaller animals, for which spatial and contrast resolution are limited. Lung CT, however, has been performed in rats for the evaluation of radiation-induced lung injury, but only lung density was considered, and radiological patterns were not precisely described [12,18,19]. In the present study, it was demonstrated that dual-helical lung CT is efficient for the detection of pulmonary sarcoid-like granulomas in the rats injected with CFA.…”

“…Measurement of the mean lung density has previously been used to study radiation induced lung injury in rats [12,18,19]. This index, however, is relatively crude and results can be influenced by many factors, including the lung area scanned and the age of the animal [22].…”

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

“…Next we assessed the level of known radiation-induced lung pathologies -vascular remodeling, pulmonary inflammation and fibrosis (3,6,7,9,(13)(14)(15)(16)(17)(18) -by scoring the histology of lung slides (Fig. 3).…”

“…Recently, we found that in concert with inflammation, vascular remodeling played a major role in the etiology of early RILD (7,8). It was shown that lung irradiation induced early vascular remodeling resulting in pulmonary hypertension (PH) and right ventricle (RV) hypertrophy eventually leading to cardiopulmonary dysfunction (7,9).…”