title: Non-invasive whole-body plethysmograph for assessment and prediction of radiation-induced lung injury using simultaneously acquired nitric oxide and lung volume measurements.
abstract: Radiation-induced lung injury (RILI) is a prevalent side effect in patients who undergo thoracic irradiation as part of their cancer treatment. Preclinical studies play a major role in understanding disease onset under controlled experimental conditions. The aim of this work is to develop a single-chambered optimized, non-invasive, whole-body plethysmograph prototype for unrestrained small animal lung volume measurements for preclinical RILI studies. The system is also designed to simultaneously obtain nitric oxide (NO) measurements of the expired breath. The device prototype was tested using computer simulations, phantom studies and in vivo measurements in experimental animal models of RILI. The system was found to improve resemblance to true breathing signal characteristics as measured by improved skewness (21.83%) and kurtosis (51.94%) in addition to increased overall signal sensitivity (3.61%) of the acquired breath signal, when compared to matching control data. NO concentration data was combined with breath measurements in order to predict early RILI onset. The system was evaluated using serial weekly measurements in hemi-thorax irradiated rats (n = 8) yielding a classification performance of 50.0%, 62.5%, 87.5% using lung volume only, NO only, and combined measurements of both, respectively. Our results indicate that improved performance could be achieved when measurements of lung volume are combined with those of NO. This would provide the overall plethysmography system with the ability to provide useful diagnostic and prognostic information for preclinical and, potentially, clinical thoracic dose escalation studies.
authors.affiliation: Department of Oncology, Medical Physics Unit, McGill University, Montreal, Quebec, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Coates
authors.forename: Norma
authors.initials: N
authors.lastname: Ybarra
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
mesh_terms: D000818:Animals; D001944:Breath Tests / Q000295:instrumentation* / Q000379:methods; D003198:Computer Simulation; D004195:Disease Models, Animal; D004867:Equipment Design; D045853:Exhalation; D020342:Finite Element Analysis; D055370:Lung Injury / Q000175:diagnosis* / Q000503:physiopathology; D008176:Lung Volume Measurements / Q000295:instrumentation* / Q000379:methods; D009569:Nitric Oxide / Q000032:analysis*; D019047:Phantoms, Imaging; D010991:Plethysmography / Q000295:instrumentation* / Q000379:methods; D011312:Pressure; D011379:Prognosis; D011832:Radiation Injuries / Q000175:diagnosis* / Q000503:physiopathology; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D012680:Sensitivity and Specificity; D013909:Thorax
chemical_list: D009569:Nitric Oxide