(a and b) Creare’s probe produced this 20-micrometer thick transverse slice through a mouse hippocampus, at a 10 micrometer in-plane resolution. (c and d) Conventional histological image of a different brain showing the same features. (Images courtesy of John Nouls and G. Allan Johnson at the Duke University Center for In-Vivo Microscopy www.civm.duhs.duke.edu.)

Scientists employed in advanced medical, biomedical, and pharmaceutical research need imaging tools that can quickly provide electronic, three-dimensional, micrometer-scale images of small animal specimens. Creare has teamed with the Duke University Center for In-Vivo Microscopy (CIVM) to develop a superconducting radiofrequency (RF) probe that enables researchers to easily produce ultra-high resolution, magnetic resonance (MR) microscope images. Although some of the key elements of this approach have been demonstrated by others before, the practical problems of maintaining the coil at resonance while operating at supercold temperatures have prevented the construction of coils that are useful for routine imaging. Creare’s cryogenic probe overcomes these difficulties through innovative mechanical and thermal design. The probe has greatly benefited ongoing brain studies at Duke by increasing the resolution of images that can be obtained by MR histology from small animal specimens. Already, researchers at Duke have made images with volume elements as small as 10x10x20 cubic micrometers.

A practical, superconducting imaging coil for histology must overcome daunting design challenges. The signal-to-noise ratio must be very high; the radiofrequency field must be highly uniform; the resonant frequency of the coil – which depends on temperature and on the size and shape of the sample – must be tuned precisely; the impedance of the sensing circuit must be maintained at 50 ohms, and the temperature of the probe must be kept constant within an extremely tight band. Creare’s MR microscopy system has been designed to overcome all these challenges:

• The superconducting RF coil enables very high signal-to-noise ratio.
• The coil is rapidly adjusted and tuned while operating at very low temperature (60 K, or 350°F below zero).
• It provides extremely stable cryogenic temperatures over long image acquisition times.
• A flexible, superinsulated conduit allows the probe to be removed from the magnet and the sample changed out easily while at cryogenic operating temperature.

The RF probes are fabricated from high-temperature superconducting YBCO material. The coils must be cooled to an operating temperature of 60 K to enable superconducting operation. Our cryogenic cooling system maintains this temperature precisely with fluctuations less than ±0.1K over cold runs that last 96 hours or more. This stable temperature limits changes in the coil’s quality factor and resonant frequency that can be caused by temperature fluctuations.

The superconducting system is currently in use at CIVM as part of on-going research to develop improved imaging techniques for small specimens. Already the probe has doubled the maximum resolution that can be attained. The cryogenic cooling system has been extremely reliable and has been used for very long runs without problems or temperature variation. CIVM is currently preparing to use the probe in a more powerful magnet to achieve even higher imaging resolution. A recent issue of the Journal of Magnetic Resonance featured the Creare/CIVM probe on the cover.

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