title: Three-dimensional accurate detection of lung emphysema in rats using ultra-short and zero echo time MRI.
abstract: Emphysema is a life-threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non-invasive pre-clinical and clinical detection and longitudinal follow-up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three-dimensional (3D) zero echo time (ZTE) and 3D ultra-short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro-computed tomography images were acquired 4 weeks after the PPE challenge. Signal-to-noise ratios (SNRs) were measured in PPE-treated and control rats. T2* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE-treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T2* values in PPE-challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE-treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE-treated and non-PPE-treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non-invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation exposure typical of micro-computed tomography.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research, In-Vivo Imaging Laboratory, Biberach an der Riss, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Core Facility Small Animal MRI, Ulm University, Ulm, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Tibiletti
authors.affiliation: Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Department of Neuroradiology, University Hospital Hamburg-Eppendorf, Germany.
authors.forename: Åsmund
authors.initials: Å
authors.lastname: Kjørstad
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research, Target Validation Technologies, Biberach an der Riss, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Birk
authors.affiliation: Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Lothar R
authors.initials: LR
authors.lastname: Schad
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research, Target Validation Technologies, Biberach an der Riss, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Stierstorfer
authors.affiliation: Core Facility Small Animal MRI, Ulm University, Ulm, Germany.|Department of Internal Medicine II, Ulm University, Ulm, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Rasche
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research, In-Vivo Imaging Laboratory, Biberach an der Riss, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Stiller
mesh_terms: D000465:Algorithms; D000818:Animals; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008168:Lung / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011656:Pulmonary Emphysema / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D059629:Signal-To-Noise Ratio
keywords: 3D UTE; COPD; ZTE; emphysema; lung MRI; micro-CT