Main Body

Investigators and Program Directors

William Shain, Phd

Research Scientist, Wadsworth Center, Translational Medicine
Center for Neural Communication Technology

School of Public Health, Biomedical Sciences
Environmental Health Sciences

Ph.D., Temple University, (1972)
Postdoctoral training, National Institutes of Health

E-mail: shain@wadsworth.org

Research Interests Continued

• 3D, Multi-spectral imaging
• Automated image analysis
• Complex impedance spectroscopy (CIS)
• Electrophysiological recordings
• Local Drug Delivery
• Microfabricated devices
• Deep-brain stimulation (DBS)
• Multidisciplinary research
• Support

3D, Multi-spectral imaging

Because of the small size of our devices (cross sections = 15x60 to 100x100 µm) conventional biochemical methods of measure are impractical. In addition they would not provide spacial or cell-specific information. Therefore, we have developed microscopic methods for assessing tissue responses. For these studies as many as 5 different labels are used to identify all cell nuclei and astrocytes, microglia, neurons, and vascular endothelia cells. 100-µm thick tissue slices are prepared using immunohistochemistry. Images are collected using confocal microscopy as a series of optical sections including the entire tissue slice. These data are then presented either as maximum-intensity projections or analyzed using our FARSIGHT image analysis toolkit and presented as rendered images, maps of cell distributions, or graphical presentation of measured characteristics.

These data are a result of experiments lead by Karen L Smith of our lab.

Automated image analysis

FARSIGHT is a toolkit of algorithms that enables automated analysis of our 3D data-sets. Four of the critical parts of FARSIGHT are nuclear segmentation - the process of identifying all of the nuclei in the dataset; cell classification - the process of correlating each nucleus with a cell specific label; registration and merging of overlapping data-sets to provide a seamless image (these can contain >50 individual fields); and validation of the automated results. The results from FARSIGHT provide a complete count of all cells, maps of cell distributions, and associations among groups of cells or distributions of cells away from insertion sites.

This work is a collaboration with Dr. B Roysam at Rensselaer Polytechnic Institute.

Complex impedance spectroscopy (CIS).

The main drawback of image analysis is that one most terminate the experiment in order to make observations and measurements. CIS provides a means of making on-line, real-time assessment of tissue organization. These measurements are also useful for better understanding electrophysiological recordings. We also propose to CIS in conjunction with microfluidic devices for controlled drug release. These measurements pass small AC potentials from each electrode into the tissue over a wide range of frequencies. We have demonstrated that these impedance measurements can be correlated with the extent of reactive responses. Ongoing research is focused at better understanding the cell responses responsible for the observed impedance changes. These data will be used to formulate a target-specific pharmacology and continued high-fidelity device performance.

This work is done by John Frampton in our lab and in collaboration with JC Williams at the University of Wisconsin-Madison.

Electrophysiological recordings

Standard extracellular recording methods are being used to measure spontaneous electrical activity, local field potentials, and sensory-evoked potentials in lightly anesthetized animals. The fidelity of these signals is critical to the integration of neural prosthetic devices in to brain-computer interface applications or for controlling artificial limbs. Experiments are designed to record in either sensory motor cortex in fields associated with hindlimb sensory and motor function or barrel cortex.

This work is done in our laboratory and in collaboration with JC Williams at the Univeristy of Wisconsin-Madison and Daryl Kipke, University of Michigan.

Local drug delivery to promote cell survival and reduce reactive cell responses.

Two different methods of drug delivery are under investigation. In the first, devices are coated with polymers/hydrogels. These materials have been selected because they are biocompatible, can be modified to control drug release, and can store sufficient amounts of drug to promote the desired biological responses. Both anti-inflammatory drugs and neurotrophins are being used. The second method of drug delivery is using microfluidics. For this approach microfabricated channels are incorporated into device designs and compounds are either allowed to diffuse from the devices or they are actively pumped. This method allows us to delivery drugs to larger volumes of the brain and to control delivery over a longer period of time.

This work is done in collaboration with CS Ober, Cornell University and ST Retterer, Oak Ridge Ntional Labs.

Microfabricated devices

Experiments are designed specifically to examine the immediate injuries of insertion, early reactive cell responses that are the reactions to the immediate injuries, and sustained reactive cell responses that are maintained for the duration of our experiments (3 months). These experiments permit study of the fate of neurons, astrocytes, and microglia, as well as angiogenesis that occurs around inserted devices. One of the focuses of this work is the development and testing of biologically derived design criteria. A key feature of these designs is an open architecture producing devices with annular vs disc-shaped electrodes and additional open spaces.

This work is a collaboration with CNCT partners and collaborators.

Deep-brain stimulation (DBS)

DBS is an effective means for controlling the symptoms of a number of neurological disorders. These methods were first developed for treating Parkinson’s Disease and have been extended to other movement disorders, certain psychiatric disorders, and epilepsy. The exact mechanism by which DBS works is not known. The goal of our experiments is analyze post-mortem human brain samples obtained from DBS patients to better understand the effects of the device and stimulation on brain cells in the target areas.

This project is collaboration with Dr. M Okun, University of Florida, McKnight Brain Institute.

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Multidisciplinary research.

All of this work is highly interdisciplinary and the synergy created by interactions among neuroscientists, electrical engineers, polymer chemists, neural engineers, and computer scientists is an essential for the success of this work.

Faculty, research staff, students, and post-doctoral trainees at the following institutions have made significant contributions to this work:

Cornell University
Frederic Haer Company
Oak Ridge National Laboratories
Purdue University
Rensselaer Polytechnic Institute (RPI)
Rutgers University-Center for Biomaterials
Seoul National University
University of Florida
University of Michigan
University of Wisconsin-Madison
Wadsworth Center

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This work has been made possible by grants and support from

Korean Science Foundation (KOSEF)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
National Institute of Neurological Diseases and Stroke (NINDS)
National Science Foundation (NSF)
Wadsworth Center, New York State Department of Health

Contact Information

Phone: (518)473-3630
Fax: (518)474-7466
E-mail: shain@wadsworth.org.