Article published in Bioscience Technology
By Steven G. Turowski, Michael Loecher, Mukund Seshadri and Richard Mazurchuk
Roswell Park Cancer Institute, Buffalo, NY
Small animal magnetic resonance imaging (MRI) techniques are currently one of the premier research tools available to probe and validate structural and functional relationships at the biosystem, cellular or molecular level. In fact, a growing number of MRI facilities dedicated to imaging small animal models of disease now exist in a variety of environments encompassing pharmaceutical, medical and basic science research. Preclinical MRI studies are typically performed at high magnetic field strengths, yielding high signal-to-noise ratios (SNRs) and soft tissue contrast compared to other available modalities.
A majority of preclinical studies, especially those that involve characterization of disease progression and response to therapy in transgenic animal models, require an elaborate experimental design using large cohorts of animals. The acquisition of these large MRI data sets can be expensive, time consuming and labor intensive. Therefore, automation techniques to improve throughput, increase efficiency and/or improve accuracy would represent a significant advance, especially with regard to screening and phenotyping animals.
Specifically, this article describes the use of a novel MRI-compatible device (SQUIGGLE motor, New Scale Technologies, Rochester, NY) that could allow researchers to remotely:
(1) administer agents to live animals in a MRI environment without image artifact,
(2) re-position samples/animals in a dynamic fashion during data acquisition, and
(3) tune and impedance match RF coils at their resonant frequency.
To demonstrate the potential utility of this device in small animal imaging, studies were carried out in a 4.7T MRI scanner dedicated for small animal imaging research.
Motors and MRI
Traditional electromagnetic motors contain ferrous metal and therefore represent a safety hazard in areas containing strong magnetic fields (i.e., contraindicated in MRI environments). Electromagnetic motors also generate their own magnetic and RF fields during operation that could result in RF arcing, causing hardware damage and undesirable image artifacts. In addition, motor operation may be influenced by static and gradient magnetic fields used during MRI data acquisition, causing the motor to function unpredictably or to become permanently damaged. To overcome these problems, our laboratory has made use of a piezoelectric motor or SQUIGGLE motor. This miniature ultrasonic motor does not generate magnetic fields and can be constructed entirely of non-ferrous materials. The potential utility of the SQUIGGLE motor in small animal imaging-related applications, including remote administration of contrast agents to animals and dynamic repositioning of the animals within the MR scanner, was investigated.
The piezoelectric motor
The SQUIGGLE motor consists of four piezoelectric ceramic plates bonded to a non-magnetic metal tube, threaded on the inside. A matching threaded screw is inserted into the tube. Two-phase drive signals cause the piezoelectric plates to vibrate at an ultrasonic frequency of 40 kHz to 200 kHz, matching the first bending resonant frequency of the tube. The motion of the plates is synchronized to make the tube vibrate in an orbital, “hula hoop” motion. This causes the screw to rotate and translate. The position and speed of the screw can be controlled with high precision.
Contrast media injection apparatus
We first used the SQUIGGLE motor to inject contrast media into a mouse during a MRI scan with the motor placed in the bore of our magnet in close proximity to the animal.
Our previous set up for performing infusions included a modified ferrous-containing infusion pump interfaced to a computer for accurate control of injection volume and delivery rates. Although functional, the device is characterized by two limitations. First, the modified infusion pump cannot precisely deliver low doses in a linear time-dependent manner. Second, the configuration generally requires > 2-3 meters of PE 50 catheter tubing to deliver injections to an animal placed at magnetic field isocenter during scanning. As a result, the dead volume in our catheter is non-trivial and approximates an injected dose volume for mice (~ 0.26 ml), resulting in an increased blood volume that could confound MRI results.
To overcome these problems, we developed a novel setup using the SQUIGGLE motor to drive a 1cc syringe connected to a PE 50 catheter (< 50 cm in total length) at a controlled speed of about 1 mm/sec (0.0185 cc/sec) when placed within the bore of a magnet.
Due to the open-loop configuration of the SQUIGGLE motor, a miniature LCD camera system and a digital time stamp were used to visualize syringe movement within the bore of the scanner. This enabled precise determination of the injection volume of the contrast agent as a function of time. The SQUIGGLE motor allowed precise delivery of low doses of the MRI contrast media in real time during data acquisition.
Automated sample re-positioning to improve image quality and throughput
Acquiring data close to magnetic field isocenter minimizes artifact in MR images. However, this is not possible without repositioning the sample for each “slice.” To circumvent this problem, we used the SQUIGGLE motor to dynamically reposition a live animal (mouse) inside the scanner during data acquisition. The SQUIGGLE motor was able to dynamically translocate the animal along the longitudinal z-axis of the magnet with precision. This not only increased the effective field of view (FOV) along the z-axis, but also improved the signal-to-noise ratio (SNR) and the overall image quality.
Generally, RF and gradient coil homogeneity is limited by the geometric shape, size and coil construction, i.e., the RF and magnetic field homogeneity diminishes as the distance from magnetic field isocenter increases. Using the SQUIGGLE motor to dynamically re-position a sample to optimize image quality or to translocate the sample in a precisely controlled fashion could permit semi-automated MRI cancer screening or morphologic phenotyping of large cohorts of animals.
Whole body small animal imaging possesses the benefit of allowing for precise sample placement, as well as observation of whole body processes as they relate to contrast/drug injection, metastatic spread or simply scanning multiple points of interest, all without having to physically move the animal. We currently have the ability to scan a relatively homogeneous FOV over a spherical diameter of 40 mm without repositioning the sample or the animal. Whole-animal scanning would require either a larger (and more expensive) RF and gradient coils with reduced SNR, or a mechanism to move the animal through the coil at a constant, precisely controlled rate. Our preliminary work in this area has yielded significant promise in this area of application for the SQUIGGLE motor.
Automated capacitor tuning and impedance matching
Finally, it should be possible to design an automated tuning/matching device using the SQUIGGLE motor for MRI applications. Currently, the procedure involves the use of a “tuning wand” to manually match the frequency and the coil impedance for each sample prior to data acquisition. We believe that an automated system based on the SQUIGGLE motor would significantly improve the accuracy and reduce the amount of time involved for this procedure, especially for large scale screening studies.
Based on our work to date, piezoelectric motors such as the SQUIGGLE motor hold great promise for use in MRI environments and to improve the efficiency and quality of preclinical MRI data acquisitions.
New Scale Technologies’ engineering team works with OEM customers to integrate SQUIGGLE motor systems into next-generation medical systems and devices designs. Learn more about our standard micromechatronics modules and custom engineering services.