Hyperpolarized Xenon functional MRI of human lungs

Xemed, Llc, Durham NH

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Abstract

[unreadable] DESCRIPTION (provided by applicant): While obstructive lung disease is the fourth leading cause of death in the US, high-resolution non-invasive functional assessment of lungs is lagging behind imaging of other vital organs. Emphysema is characterized by a sudden irreversible decay of lung tissue, reducing the surface area for gas exchange while increasing the alveolar void dimensions. MRI diffusion-weighted sequences with hyperpolarized gases measure diffusion distance versus time, probing the void spatial dimensions. Although 3He diffusion MRI exposes emphysema's ravaging effects in mid and late stages, the fast diffusion of 3He (atoms travel normal alveolar diameters in less than a millisecond) interferes with early diagnosis and quantitative tracking of the disease. The lower diffusion constant of xenon offers sensitivity to restrictions to diffusion that are a factor of 3.7 smaller (along one dimension) than those probed with 3He, allowing detection of early emphysema when alveolar volumes are a factor of fifty smaller. Furthermore, the solubility of xenon in lung surface tissues offers a second, complementary measure of lung microstructure. Unlike 3He which is expensive, not found in nature, and only occurs as a byproduct of weapons development, xenon is cheap and abundant and therefore commercially viable. The primary obstacle to exploiting these advantages, low polarization using routine production techniques, has now been overcome. The new conter-flowing polarizer developed at UNH and Xemed offers a factor often higher magnetization output than the best competing designs. We will demonstrate that hyperpolarized xenon-129 MRI exceeds the sensitivity of 3He to early emphysema by performing the following measurements in healthy human subjects: 1. We will determine alveolar dimensions by measuring average diffusion distance as a function of time 2. We will measure local alveolar surface-to-volume ratio using xenon polarization transfer between the gas space (volume) and the xenon dissolved in the lung tissue (surface). Through multiple measurements under identical conditions, we will determine the internal consistency, reproducibility, and sensitivity to changes of these measurements. Demonstration of quantitative properties of this protocol could lead to new research into triggers for emphysema and therapeutics for slowing its progress, resulting in commercialization opportunities. [unreadable] [unreadable] [unreadable]