Medical Imaging

Projects

Imaging Applications | Polarization Physics | Cross-disciplinary Education | Technology Advancement

The UNH Center for Xenon Imaging is pursuing with its collaborators a number of projects broadly organized around four themes:

Imaging Applications

Functional lung imaging - - The UNH group is investigating the potential applications of hyperpolarized xenon in the gas phase for noninvasive diagnostic functional imaging of lungs. Functional imaging describes imaging that represents a functional attribute of an organ distributed in space over the volume of the organ. In particular, we intend to demonstrate two complementary methods for determining the lung surface-to-volume ratio, a microstructural parameter critical to gas exchange function in the lung that becomes sharply reduced in lungs with emphysema. A quantitative measure of this parameter could provide a marker identifying emphysema in its early stages.

One method we will investigate for measuring this parameter of lung microstructure is restricted diffusion. In free space, the average distance a gas atom or molecule diffuses in a given amount of time has a fixed relationship (square root) to the amount of time allowed for its diffusion. If barriers such as the walls of the microscopic alveoli in lungs are encountered by the gas atoms, then the average distance is reduced. If boundaries are farther away, more time is required before most atoms encounter the boundary. By studying the gas diffusion distance as a function of time, the geometry of the restrictive barriers can be determined. The low diffusion constant of xenon will allow more precise determinations than those presently performed with helium.

The second method we will investigate exploits the solubility of xenon in tissues and the change in the resonant frequency (chemical shift) of dissolved xenon atoms. First, xenon atoms are allowed some time to dissolve into the lung surface. Second, the dissolved atoms are selectively depolarized. Third, some time is allowed for these depolarized atoms to diffuse back into the gas phase. If this sequence is repeated many times, the volume of gas will become partially depolarized by an amount proportional to the surface-to-volume ratio.

Low-field imaging technology - - In conventional magnetic resonance imaging the degree of polarization of the protons in tissues is proportional to the strength of the magnetic field of the imager. Consequently hospitals require and companies provide high-strength superconducting magnets for high-resolution MRI. In contrast, the polarization in our xenon is accomplished with lasers, removing the requirement for a large superconducting magnet. It becomes possible to consider simpler, lower cost, open geometry magnets. Furthermore, imaging of the gas space in lungs is confounded by the high magnetic fields because the mismatch in magnetic susceptibility between the gas space and lung tissue produces random magnetic field gradients that dephase the gas atoms during imaging.

Our collaboration is working on demonstrating our techniques for measuring lung surface-to-volume ratio using a low-field (0.2 tesla) clinical scanner, modified to accommodate the lower resonant frequency of xenon (relative to protons in living tissue). Modifications include adding a new, versatile research console to control the imaging sequences, and fabricating special coils at the lower frequency of 2.367 MHz.

Ultra-low-field imaging - - We have pioneered ultra-low-field imaging by assembling a complete MRI scanner operating at 0.005 tesla with frequencies between 50 kHz and 150 kHz. Working with collaborators from the Brigham and Women's Hospital, Mirtech, and the Harvard-Smithsonian Center for Astrophysics we accomplished lung imaging in a human in vivo.

Functional dissolved-state imaging - - We are examining the potential of hyperpolarized xenon dissolved-state imaging as a contrast agent for imaging cardiovascular health, differentiating malignant from benign growths, and determining brain functional characteristics. These life-saving techniques could become possible because of the intrinsic properties of xenon. Xenon has a high solubility in blood and tissues. It passes readily from the lungs to the bloodstream without losing significant polarization. It maintains its polarization for ten to twenty seconds while it is transported throughout the arteries and highly perfused organs. It displays a characteristic frequency (chemical shift) for different tissue compositions.

Biomedical imaging simulations - - We have implemented a numerical simulation of xenon gas dynamics in vivo, tracking the concentrations of both polarized and total xenon, including the inhaled volume, the alveolar concentration, the pulmonary blood concentration, the peripheral artery concentration, and the peripheral tissue concentration. The results of our simulation are consistent with those of Martin and of Peled(corrected). Partition coefficients and transport times can be modified for application to measurements of blood volume and perfusion to diagnose cancer, assess cardiovascular disease, or image brain function.

Polarization Physics

Numerical simulations - - The xenon polarization technology developed at UNH has been guided by a program of numerical simulations that incorporate the relevant known physical processes and current values of the fundamental spin-exchange constants. Qualitative agreement is good and the dependence of the output on various parameters is observed, however quantitatively the experiment differs from the calculation by 30% or more. We are working to improve the numerical precision of the calculations by extending the treatment to two-spatial dimensions and extending the description of low-pressure spin exchange and depolarization. A precise description of the polarization process would allow us to consider alternative polarizer geometries, specificly smaller and more practical designs.

Diagnostics - - As discussed above, agreement between the numerical simulation and the polarizer output would give confidence in predicted performance of smaller, more compact, more robust designs. The disagreement could stem from incorrect assumptions about physical state variables that are important to the performance of the polarizer. For example, we make assumptions about the alkali density and the gas temperature in the polarizing column that may not always be justified. We are adding diagnostics to measure rubidium density, rubidium polarization, and measure the xenon polarization using more than one method.

Cross-disciplinary Education

Practical training - - The UNH group provides a multi-faceted learning environment for cross-disciplinary education. Due to our close ties with the UNH Nuclear Physics Group, Research Scientists can have joint appointments. We find that the broad spectrum of opportunities to engage in fundamental nuclear physics as well as contribute at the forefront of biomedical research attracts top postdoctoral scientists to choose the UNH Center. Graduate and undergraduate student Research Assistants master diverse technologies to complete projects, including electronics, computer hardware and software control, gas flow and vacuum, high and low power laser and optics, RF coil and system development, cryogenics, magnetics, mechanical design and implementation, thermal heating and cooling systems, and numerical simulation. Undergraduate laboratory assistants develop skills in some of these areas.

Coursework - - We developed a new "special topics" course in "Polarization and Magnetic Resonance Imaging of Noble Gas Nuclei" which was offered in Spring, 2002. This course provided formal preparation for graduate and undergraduate students involved in the program.

Seminars - - An ongoing series of seminars at the Brigham and Women's Hospital is complemented by occasional seminar offerings at the University of New Hampshire.

Technology Advancement

Refinement - - The UNH research group is committed to internal and ongoing refinement of the polarization technologies we have pioneered, including increasing the available laser power, incorporating optics improvements, increasing the quantity of xenon produced, increasing the fraction of polarized xenon remaining after a freeze-thaw cycle, increasing the uniformity of the magnetic field while simultaneously shrinking its size, extending the capabilities of the gas-flow and vacuum system, reducing the oven's heat loss, and improving the NMR measurements.

Utilization - - Through our collaborative Bioengineering Research Partnership with the Brigham and Women's Hospital, we have developed and assembled a facility for transporting polarized xenon from the production site in our lab at UNH to their imaging facilities in the Boston area. Once this is underway, we will direct our efforts to duplicating our polarizer for remote siting, either in a mobile vehicle or in a dedicated room at the imaging facility.