In Vivo Studies Core
The In Vivo Studies Core will provide specialized equipment needed for the study of gastrointestinal function in humans and living animals. Specialized equipment for the performance of human motility studies, acid and pancreatic enzyme secretion studies, intestinal perfusion studies and various breath tests will be available through the GI Physiology laboratory under the direction of Dr. Owyang.
With the recent development of the electronic barostat, the intestinal and colonic peristaltic reflex in humans can be studied. Applications of miniature strain-gauge pressure transducers, coupled with the simultaneous use of nuclear scintigraphy to study GI transit, allows correlation of motility patterns with luminal contents movement. This technique has been used by a number of investigators to study patients with obscure diarrhea or constipation. Patients with constipation associated with IBS frequently demonstrate high amplitude non-peristaltic contractions. These are associated with a delay in luminal contents movement. On the other hand, constipation secondary to colonic inertia problems frequently showed a lack of contractions, which resulted in delayed colonic transit. Information obtained through these types of studies provides important insights into the pathophysiology of motility disorders.
The GI Physiology lab is also equipped for the performance of electrogastrography (EGG). This technique involves placement of cutaneous electrodes across the abdomen. The electrodes are connected via direct nystagmus couplers to a chart recorder to provide a continuous display of gastric myoelectric activity. The chart recorder is interfaced with a personal computer via an analogue-to-digital converter. Signals are digitized at 1Hz and filtered above 15 cycles per minute and below 0.5 cycles per minute to remove high and low frequency noise. With the development of better electrodes and improved software, the EGG can now reliably record gastric slow waves in humans and has been used extensively by Center investigators to study patients with nausea and vomiting.
In collaboration with Dr. Beydoun from the Department of Neurology, the In Vivo Studies Core has established electrophysiological techniques to measure evoked cortical and spinal potentials for evaluation of visceral and afferent pathways. Equipment for EEG recording is housed on the first floor of the University Hospital in the EEG laboratory of the Department of Neurology. This technique was frequently used by Drs. Chey, Owyang, Hasler, and Wiley. In collaboration with Dr. Kirk Frey (Division of Nuclear Medicine), the In Vivo Studies Core has made available CNS imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to study brain regions that are involved in processing gut sensations. PET scanning is an expensive and sophisticated technique that also requires facilities for generation of radioisotopes, which restricts its availability to specialized centers. The average cost of a PET facility together with a cyclotron is in excess of $5 million. Similarly, fMRI is also very costly to set up and difficult to operate without the appropriate expertise. The In Vivo Studies Core has successfully addressed these challenges by cultivating a close working relationship with Dr. Frey and Dr. Rick Gracely, an expert on fMRI. This equipment is available for the use of Center Investigators following review by the internal PET and fMRI executive committees. This equipment is housed in the Radiology Department at the University Hospital.
The In Vivo Studies Core is fully equipped for a full range of acute and chronic gastric and pancreatic secretion studies in both large and small animals. Equipment for electrophysiologic and motility studies and for non-invasive measurement of animal visceral blood flow are also available in the animal in vivo study program based in room 6526 of the MSRB I building. This laboratory also permits surgical placement of serosal silver-silver chloride electrodes, which provide a reliable method of monitoring GI myoelectric activity and also permit “pacing” of discrete segments of the digestive tract. In addition, this laboratory is equipped to perform small intestine and colonic transit studies using non-absorbable markers introduced into the GI tract. Recently Dr. Jen Yu Wei has introduced an in vitro isolated stomach vagus preparation to investigate the action of peptides on gastric vagal afferents. This preparation completely eliminates any influence of the CNS and/or systemic responses. It demonstrates unequivocally the actions of the test substances at the level of the vagal afferent. Dr. Wei has also helped to develop a technique of isolating the vagal gastric branch for electrophysiological studies. Neural signals are amplified, filtered and monitored on an oscilloscope. The signals are then sent to a PC-based CED data acquisition system for online analysis and to an analog data recorder for offline analysis using CED spike detection software. Single unit recording can be identified from the patterns of the discharge.
A new service provided by the In Vivo Studies Core is the capability to perform in vivo cellular and molecular imaging studies. This is done in conjunction with the Michigan Small Animal Imaging Resource Center in the Department of Radiology and is housed in the Kresge II building, a short walk from MSRB I. The Center is equipped with a number of high tech imaging modalities and equipment. These include :
- Xenogen’s IVIS imaging system for bio-luminescence imaging.
- ImTek microM-Computer Aided tomography system, which has intrinsic resolutions less than 0.05mm and produces reconstructed images with spatial resolution less that 0.1 mm This microcomputer tomography is suitable for studying internal organs of mice with the same accuracy available to a physician studying human anatomy.
- Micropositron Emission Tomography, made by Concorde (microPET). This instrument is dedicated to small animal imaging studies and is based on PET technology. Non-invasive, in vivo imaging with microPET allows serial and longitudinal studies to be performed in the same animal, giving investigators the opportunity to follow a single animal over time and to monitor the effects of intervention on disease progression and outcome. It is also ideal for studying genetically modified animals and will therefore be a particularly valuable tool in animal models which exhibit high variability, and in situations in which particular animals are unique or valuable.
- Magnetic resonance imaging and spectroscopy of animal models. Magnetic resonance experiments are performed on several state of the art systems including 9.4T, 22-cm Horizontal Bore Varian UnityInova and 7T, 18-cm Horizontal Bore Varian UnityInova.