MRI Used to Visualize Microscopic Flow

Of the tools used to examine material structures at the atomic and molecular scales, there is none better than nuclear magnetic resonance (NMR) spectroscopy and its daughter technology magnetic resonance imaging (MRI). Now, the latest development from the research group of one of the world's foremost authorities on NMR/MRI technology has the potential for NMR/MRI results that are better and faster than ever before--a million times faster.

Through a combination of remote instrumentation, JPEG-style image compression algorithms and other major refinements, chemist Dr. Alexander Pines and members of his research group have been able to use NMR/MRI to image materials flowing through microfluidic "lab-on-a-chip” devices and zoom in on microscopic objects of specific interest with unprecedented spatial and time resolutions. Dr. Pines holds joint appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab; Berkeley, CA, USA) and the University of California (UC) at Berkeley (USA).

"What excites me most about this new methodology is the possibility of a mobile, chip-based NMR/MRI platform for microfluidic analysis. Who knows? This might turn out to be useful for chemistry and biomedicine,” remarked Dr. Pines, an internationally recognized leader in the development of NMR technology, who is a faculty senior scientist in Berkeley Lab's materials sciences division and a professor of chemistry at UC Berkeley.

This latest study, which focused on MRI, has been reported October 7, 2010, in the journal Science. Coauthoring the paper with Dr. Pines included Dr. Vikram Bajaj, who is still a member of the Pines' group. According to Dr. Bajaj, first author on the Science article, "We have been able to conclusively demonstrate the ability to record microscopic images of flowing macroscopic objects without loss of sensitivity, something that is impossible in conventional MRI. We were also able to illustrate how MRI can be used to measure flow dynamics quantitatively and with high spatial resolution in real microfluidic devices. The spatial resolution we achieved is sufficient to capture the results of hundreds or thousands of parallel assays on a microfluidic device. Furthermore, we recorded these images approximately one million times faster than could be done with a conventional MRI experiment. This means that experiments which would have taken years to complete are now practical considerations.”

NMR/MRI signals are made possible by a feature found in the atomic nuclei called "spin,” which makes the nuclei act as if they were bar magnets. Obtaining an NMR/MRI signal depends upon an excess of nuclei in a sample with spins pointing either "north” or "south.” In the signal-encoding phase of NMR/MRI, the nuclei are exposed to a magnetic field and subjected to radiofrequency pulses so that they absorb and re-emit energy at signature frequencies. In the signal-detection phase of NMR/MRI, the frequencies of the encoded signals are either directly measured to obtain a spectrum (NMR), or used to obtain a second, spatially encoded signal that can then be translated into images (MRI).

MRI has become a fundamental part of modern medicine, providing physicians with a diagnostic tool that is noninvasive, quick, and involves no ionizing radiation that can damage cells and tissue. However, traditional MRI requires huge doughnut-shaped machines that fill an entire room and are extremely expensive to buy and operate. Recently, Dr. Pines and his group have taken great steps towards making NMR/MRI technology compact, portable, and comparatively inexpensive. It began with the decoupling of the NMR/MRI signal encoding and signal detection processes, which made remote NMR/MRI possible and widened the technology to lab-on-a-chip microfluidic assays of gases and liquids. With these new developments, Dr. Pines and his group have laid the foundation for new NMR/MRI applications in portable chemical and biomedical analysis.

"Our goal is to develop NMR/MRI appliances for portable chemical analysis of complex mixtures, including blood, urine, and saliva,” Dr. Bajaj stated. "Ultimately, we would like to make it possible to use NMR/MRI in point of care clinical analysis.”

In their new Science study, Drs. Pines and Bajaj and their coauthors described how they were able to apply MRI technology to research involving microscopic flow through microfluidic or biologic channels, or through porous materials. The key was the incorporation of several new elements into their remote NMR/MRI configuration. This included the fabrication of microsolenoid MRI probes with demountable microfluidic device holders, the design of remote MRI sequences for spatial encoding in the presence of motion, as well as for velocimetric measurements, and the use of JPEG-style compressive sampling algorithms for accelerated image encoding.

"The combination of remote NMR/MRI methods with these new elements spectroscopically mimics the implantation of a coil around a microscopic feature of interest and allows us to zoom in on the microscopic details of microfluidic flow dynamics in three spatial dimensions,” concluded Dr. Bajaj. "The mechanism of remote detection is analogous to that of a magnetic recording tape on which complex data are first encoded and later read out by a single stationary detector as the tape advances.”

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