Multimodality Functional Imaging in the Rodent Lungs

Abstract

The ability to image ventilation and perfusion enables pulmonary researchers to study functional metrics of gas exchange on a regional basis. There is a huge interest in applying imaging methods to study the large number of genetic models of pulmonary diseases available in small animals. Existing techniques to image ventilation and perfusion are often associated with low spatial resolution and ionizing radiation. Magnetic Resonance Imaging (MRI) has been demonstrated successfully for ventilation and perfusion studies in humans. Translating these techniques in small animals remains challenging. This work addresses the ventilation and perfusion imaging in small animals using MRI. Qualitative ventilation imaging in rats and mice is possible and has been demonstrated using MRI, however perfusion imaging remains a challenge. In humans and large animals perfusion can be assessed using dynamic contrast-enhanced (DCE) MRI with a single bolus injection of a gadolinium (Gd)-based contrast agent. But the method developed for the clinic cannot be translated directly to image the rat due to the combined requirements of higher spatial and temporal resolution. This work describes a novel image acquisition technique staggered over multiple, repeatable bolus injections of contrast agent using an automated microinjector, synchronized with image acquisition to achieve dynamic first-pass contrast enhancement in the rat lung. This allows dynamic first-pass imaging that can be used to quantify pulmonary perfusion. Further improvements are made in the spatial and temporal resolution by combining the multiple injection acquisition method with Interleaved Radial Imaging and 'Sliding window-keyhole' reconstruction (IRIS). The results demonstrate a simultaneous increase in spatial resolution (<200>um) and temporal resolution (<200>ms) over previous methods, with a limited loss in signal-to-noise-ratio. While is it possible to create high resolution images of ventilation in rats using hyperpolarized 3He, extracting meaningful quantitative information indicative of changes in ventilation is difficult. In this work, we also present a signal calibration technique used to normalize the signal of 3He to volume of 3He which can then be used to extract quantitative information of changes in ventilation via normalized difference maps. Combining the techniques for quantitative ventilation and quantitative perfusion we perform studies of change in ventilation/perfusion (V/Q) before and after airway obstruction in rats. The technique is sensitive in detecting statistically significant differences in the heterogeneity of the distribution of V/Q ratio.