Title: Optical Stimulation of Neural Tissue
Principal Investigator: Peter Konrad, M.D., Ph.D.

For over a century, the traditional method of stimulating neural activity has been based on electrical methods, which has undergone few modifications over the years and remains the gold standard to date. We report a technological breakthrough in neural stimulation that uses low intensity infrared laser light to elicit compound nerve and muscle potentials instead of electrical energy. We show that infrared laser light at relative valleys of tissue absorption can be used to consistently and reproducibly stimulate peripheral nerves in frogs and rats in vivo with no appreciable tissue damage using radiant exposures well below ablation threshold. Results demonstrate optical stimulation can circumvent many of the limitations of electrical stimulation, including lack of spatial specificity and electrical artifacts that limit data analysis and make simultaneous excitation and recording from adjacent nerve fibers difficult.

Optically induced potentials are spatially precise, highly controlled and artifact-free. Several experiments were performed using the sciatic nerve in vivo to verify the physiologic validity of optical stimulation. Application of a depolarizing neuromuscular blocker resulted in a measurable CNAP and loss of CMAP confirming normal propagation of impulses from nerve to muscle upon optical stimulation. The similarity in the shape and timing of the signals from optical and electrical stimulus show conduction velocities are equal. These traces imply the measured action potentials are identical regardless of excitation mechanism.

Histological analysis of 3-5 day survival studies shows no discernable tissue damage with chronic stimulation. Thus, optical stimulation presents an innovative approach to contact-free neural activation that has major implications to clinical neural stimulation; including higher spatial resolution in functional mapping, partial resection in blocked nerves, and the potential of implantable neuroprosthetics with compact laser diodes.

Note: This abstract submitted by Dr. Konrad, MD, Assistant Professor of Neurosurgery and Director of Functional Neurosurgery at Vanderbilt University Medical Center was selected for inclusion in the 2004 Press Book compiled by the Society of Neuroscience SfN) and distributed in advance of their annual conference. The SfN includes in the Press Book only those abstracts representing scientific work of great significance. The abstract, “Optical Stimulation of Neural Tissue,” was one of 600 preferred from among over 16,000 submissions.

Title: Cellular Therapies for Malignant Gliomas
Principal Investigator: Moneeb Ehtesham, M.D.

Title: Plasma tumor-specific DNA as a biomarker for glioma
Principal Investigator: Kyle D. Weaver, M.D.

Recent advances in brain tumor research suggest the imminent development of effective treatments. Unfortunately, our ability to safely and accurately diagnose brain tumors and evaluate treatment response lags behind. It is imperative that these diagnostic deficiencies be corrected in concert with treatment advances.

It is well known that many cancers secrete their genetic material (DNA) into the blood. This DNA carries a unique tumor “fingerprint” and is not found a healthy person’s blood. It can be used to estimate amount of tumor, assess treatment response, and predict survival in some cancers, and only requires a blood draw, but has not been evaluated in brain tumors. We have demonstrated that brain tumors shed their unique DNA into the blood just as other tumors do.

We plan to develop this tumor-specific DNA in the blood into a biomarker to assist with the diagnosis of tumors and assess the response to therapy. To do so, we will identify patients needing an operation to remove a brain tumor. A piece of tumor will be removed for genetic fingerprinting and a blood sample taken to determine if it contains brain tumor DNA also. If so, the patient will be followed with MRI scans and blood draws. The type and amount of brain tumor DNA in the blood will be correlated with the patient’s clinical condition, amount of tumor on MRI, and survival. This will allow the development of a new, genetic test to better care for brain tumor patients and precisely guide their treatment.