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Magnetic Resonance
^ High-Resolution Optical Imaging of Biological Cells and Tissue Using Optical Coherence Tomography and Multiphoton Microscopy
S. A. Boppart*
Department of Electrical and Computer Engineering; Beckman Institute for Advanced Science and Technology

Optical coherence tomography (OCT) and multiphoton microscopy (MPM) are two emerging high-resolution optical imaging techniques. OCT is analogous to ultrasound, except reflections of near-infrared light are detected (rather than sound). With micron-scale resolutions and real-time acquisition rates, OCT has been applied to a wide range of biological and medical specialties. An integrated microscope combining these two complementary optical techniques is being constructed. OCT can image cell and tissue microstructure while MPM is used to label cells site specifically using fluorescent markers. This integrated microscope will be a powerful investigative tool for imaging biological processes and for diagnosing medical and surgical pathology.

^ Integrated Optical Coherence Tomography and Multiphoton Microscopy for Microfluidic System Analysis and Molecular Beacon Monitoring
S. A. Boppart,* D. J. Brady, L. M. Raskin, M. Balberg
National Science Foundation Biophotonics Partnership Initiative, #BES-0086696; Beckman Institute for Advanced Science and Technology

The microfabrication of bioMEMS and microfluidic systems is becoming increasingly complex, frequently incorporating three-dimensional structures into design parameters. The goal of this project is to develop an integrated microscope combining optical coherence tomography (OCT) and multiphoton microscopy to investigate microstructure and function within microfluidic systems. Optical Doppler OCT will map fluid flow velocities and three-dimensional flow profiles through these microsystems. Researchers will utilize molecular beacons as fluorescing markers for pathogen detection. Multiphoton microscopy will detect the spatial distribution of these fluorescing molecules. These results will lead to improved designs of microfluidic bioMEM systems for detecting environmental or medical pathogens.

^ Analysis and Design of RF Resonators for MRI Applications
J. Jin,* R. L. Magin, A. G. Webb
National Science Foundation, ECS 94-57735

RF resonators, also known as RF coils, RF antennas, and electromagnetic probes, are crucial devices for obtaining high-quality magnetic resonance images for clinical diagnosis. In this project, researchers develop numerical methods for analysis and design of such resonators for MRI applications. Specific mathematical models will be developed for low- and high-field MRI systems, which may include high-frequency phase variation and bioeffect dosimetry for RF fields.

^ Constrained Spectroscopic Imaging
Z. P. Liang,* P. C. Lauterbur*
National Institutes of Health, 1R01CA51430-01A4

Magnetic resonance spectroscopic imaging promises to provide an entirely new way to examine the dynamics of human biochemical processes in vivo noninvasively. However, its practical applications have been limited because of low sensitivity and long imaging time. The primary objective of this research is to develop mathematical methods to effectively utilize the readily available anatomical information to constrain the spectral distribution to reduce imaging time without compromising spatial resolution.

^ Functional Brain Imaging
Z. P. Liang,* J. Ji
National Science Foundation, BES 95-02121; Beckman Institute for Advanced Science and Technology

The primary objective of this project is to develop new signal-processing algorithms for detecting brain activities from functional MRI data. Researchers are investigating a wavelet-transform-based filtering and t-test method for signal detection and a multiscale method for image registration and motion correction.

^ MR Imaging of Time-Varying Objects
Z. P. Liang,* Y. Bresler,* J. Ji, A. Sen Gupta, A. Guo
National Science Foundation, BES 95-02121; National Institutes of Health, NIH-R21-HL062336

Conventional MR imaging techniques have been widely used to obtain high-resolution images from stationary objects. For time-varying objects such as the beating heart, however, significant image artifacts often arise which render the image useless. This project aims to develop a new class of data acquisition and image reconstruction methods for real-time imaging of cardiac structures and functions.

^ An Integrated NMR
R. L. Magin,* A. G. Webb
National Science Foundation, DBI 96-05829

Microlithographic and MEMS technology are being used to integrate the individual components of the receiver for nuclear magnetic resonance. This leads to advantages in packaging for planar microcoils and increases in the signal-to-noise ratio.

^ In Vivo MRI Thermometry Using New Functional Imaging Agents
A. G. Webb*
Whitaker Biomedical Engineering Foundation

Fluorine- and proton-based phase-transition agents are being synthesized for in vivo temperature mapping using magnetic resonance imaging. Applications to hyperthermia treatment of cancer are being investigated.

^ Applications of NMR Microspectroscopy to Combinatorial Chemistry
A. G. Webb,* R. Subramanian, J. V. Sweedler
Smith Kline Beecham

Combinatorial chemistry is the most recently developed synthetic pathway whereby up to a million new therapeutic drugs can be produced simultaneously. The very small quantities of material (less than 100 pmoles) preclude structural identification by traditional high-resolution NMR. Our efforts are concentrated on designing RF microcoils for operation at high magnetic fields (>11 T) for efficient detection of these chemical products.

^ Nanoliter Volume Nuclear Magnetic Resonance
A. G. Webb,* J. V. Sweedler
National Institutes of Health, PHS 1R01GM53030-01

The aim is to develop microscopic hardware so that single-cell imaging and spectroscopy experiments can be run using the model system Aplysia californica. Using techniques such as diffusion-ordered spectroscopy, the physical environment of neuropeptides within vesicles can be determined, giving valuable information on the mode of action of these metabolites.

^ Nuclear Magnetic Resonance Microimaging
A. G. Webb*
National Science Foundation, DBI 97-22320

Using microscopic NMR coils and small magnetic field gradients, the resolution of NMR microimaging can theoretically be improved to 1 to 2 cubic microns. Researchers are investigating the mechanisms which limit resolution and devising new methods to overcome these limitations. Biological experiments on spinal cord tissue are also planned.

^ Ultrahigh Field Probes for Magnetic Resonance Imaging and Spectroscopy
A. G. Webb,* S. J. Blackband, T. H. Mareci
National Science Foundation

Nuclear magnetic resonance microprobes are being constructed for operation at the highest frequency magnets in the world at the National High Magnetic Field Laboratory at Tallahassee, Fla. Coil characterization includes measurements of self-resonant frequencies and magnetic susceptibility for different geometries. High-resolution spectroscopy and microimaging experiments are being performed.


Summary of Engineering Research