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EPR and NMR Laboratories

Harold Swartz, MD, PhD, is Radiology's Director of Scientific Research, and he directs the Electron Paramagnetic Resonance Center.  Dr. Risto Kauppinen joined the staff as Director of the Biomedical NMR Center in June, 2007. Both of these laboratories have extensive funded projects, as described below. 

The Electron Paramagnetic Resonance (EPR) Center conducts EPR spectroscopy to measure oxygen and other parameters in living systems. It is the world's only active clinical EPR program and is internationally recognized as the leading site for EPR developments. One of the clinical EPR studies focuses on measurement of oxygen in the feet, a procedure with application for patients with peripheral vascular disease, especially diabetics. A second clinical EPR study focuses on measurement of oxygen in tumors, with application for establishing therapeutic efficacy and optimizing therapy for individual patients. A third project used in vivo EPR to measure radiation dose after-the-fact, a measurement of great importance for dealing with incidents due to terrorism or nuclear accidents or nuclear war. Hal Swartz, MD, PhD, directs this laboratory.

The Biomedical NMR Center has a state-of-the-art high-field NMR (7T) magnet for measurements in animals. It is utilized extensively for collaborative research with other investigators at Dartmouth and for experimental studies in Radiology. There is also a unique in vivo optical spectroscopy program, closely linked with both the NMR and the EPR laboratories, which utilizes both visible and NIR light spectroscopy.  Dr. Risto Kauppinen joined the staff as Director of the Biomedical NMR Center in June, 2007.

The funding supporting the research in these two laboratories is described in the sections below (organized according to funded grants).

EPR Center for the Study of Viable Systems

A grant from NIH supports this center in developing and applying in vivo EPR. This project's major goals are to: 1) improve instruments for in vivo EPR; 2) develop and improve resonators; 3) develop transportable versions of instruments to use in various clinical and other settings; 4) develop technology to facilitate the use of in vivo EPR in large subjects, including human subjects; 5) develop instrumental approaches for in vivo EPR; 6) improve methods for in vivo spin trapping; 7) improve methods for obtaining and analyzing EPR spectra in vivo. Dr. Hal Swartz is PI on this grant.

Measurement of pO2 In Vivo and In Vitro

This NIH program project has the following goals: (1) develop EPR oximetric materials and techniques, and (2) advance understanding of oxygen dependent physiology and pathophysiology in various organ systems and/or pathological states, especially cancer and changes in the vascular system. Centered at Dartmouth, with Dr. Hal Swartz as PI, this grant supports collaborative research at the Catholic University of Louvain in Brussels, Belgium, and the Chemistry Department at Dartmouth.

Use of In Vivo EPR for After-the-Fact Measurement of Radiation Dose

This independent research project within the "Center for Biophysical Assessment and Risk Management Following Irradiation," is administered by the University of Rochester under an NIH grant. The objective of this project is to determine, immediately after an incident, whether individuals have received a radiation dose that could result in acute clinical symptoms. It uses in vivo EPR to measure radiation in teeth of potentially exposed individuals, providing a simple method for such screening. The research involves developing both instruments and methods. Dr. Hal Swartz is PI on this grant.

Near Infrared/MR System for Imaging Brain Oxygenation

The major goal of this NIH proposal is to combine the technologies of MR and near-infrared spectroscopy to provide spatially resolved near-infrared images for studying brain oxygenation during physiological and pathophysiological stress. Dr. Hal Swartz is PI on this grant.

EPR Measurements of Brain Tissue pO2 and Oxidative Stress during Hyperbaric Oxygen Therapy Following Stroke

This project, funded by a grant from the GEMI Fund of Linde Gas Therapeutics, Lidingo, Sweden, aims to understand the effects of oxygen therapy in treating ischemic stroke. Treatment with elevated amounts of oxygen could improve stroke outcomes by improving brain-tissue oxygenation. Using a rat model of acute stroke, we are applying EPR spectroscopy to study brain tissue oxygenation and free-radical generation during the administration of oxygen therapy. Measurements with hyperbaric oxygen will be done using a novel hyperbaric chamber that can be placed in the clinical EPR spectrometer and used simultaneously. Ben Williams, PhD, Radiology Research Assistant Professor, is PI on this grant.

Imaging the Neocortex with Visible Light Spectroscopy

The goal of this NIH-funded project is to develop a system that can image the oxidation state of mitochondrial cytochrome c, as well as the absolute hemoglobin content and saturation with high resolution from the cortex of rats and mice. We have applied this system to questions of cerebral oxygenation during normal brain function, and to small animal models of stroke, applications to which the system is particularly suited. Roger Springett, PhD, Radiology Research Assistant Professor, is PI on this grant.

Portable Post-Radiation bio-Dosimeter

This project is  in collaboration with Resonance Research, Inc., Billerica, MA and is supported by the Department of Defense, Advanced Research Projects Agency .  This research is aimed at the development of a clonable EPR dosimetry instrument that could provide a unique and effective solution to a critical military problem: how to determine if an individual has received a dose of ionizing radiation that is likely to lead to acute clinical effects. The solution proposed is the development of a hand held or easily transportable dosimeter that can, after-the-fact, rapidly and accurately measure the dose received by making measurements in the teeth with EPR.  Dr. Hal Swartz is PI on this project.

Dosimeter for Field Use for the Military

This project is supported by the Defense Threat Reduction Agency (DTRA), which is aimed at producing a transportable EPR dosimeter that can be utilized in the field for the military.  Dr. Hal Swartz is PI on this project.

Use of Radiation-Induced Paramagnetic Centers in Environmental Objects to Measure Radiation Dose After-The-Fact

This project is funded by The Institute for Security Technology (ISTS) at Dartmouth College.  The overall experimental plan will focus on measuring radiation-induced paramagnetic centers in materials that are likely to be on or near people undergoing their usual activities.  We  currently have 7 Dartmouth students who, under supervision by staff of the EPR Center, are studying the utility as dosimeters of non-living material, such as articles of clothing and other materials that are likely to be in the immediate vicinity at the time that a radiation exposure would occur.  A variety of such materials have long-lived radiation induced signals that are proportionate to dose.

THE FOLLOWING GRANTS ARE SCHEDULED TO BE FUNDED AND WILL BEGIN ON JULY 1, 2007.

Determination of Clinical Feasibility of EPR Oximetry of Tumors 

The overall objective of this project, which is funded by NIH, is to demonstrate the clinical feasibility of using in vivo  EPR oximetry to obtain clinically useful information from tumors in patients. It is the first clinical EPR study ever funded by NIH. It will use the unique capabilities of in vivo EPR oximetry to advance cancer therapy by making repeated non-invasive measurements of tumor pO2 and using this information to individualize tumor therapy.  Dr. Hal Swartz is PI on this grant.

Development of EPR and NIR Oximetry for Diabetic Foot

This  project, funded by NIH, will apply two emerging techniques: electron paramagnetic resonance (EPR) oximetry and near infrared spectroscopy (NIR) to measure tissue oxygenation directly and reliably in healthy volunteers. The ultimate aim is to extend the techniques to diabetic patients for clinical management of the disease.  Md. Nadeem Khan, PhD, Radiology Research Assistant Professor, is PI on this grant.

Monitoring Oxygen Repeatedly for Hypoxic Tumor Therapy

This project is funded by NIH.  The goal is to demonstrate, under realistic conditions, that in vivo EPR oximetry can provide repetitive data on tumor oxygenation during the course of therapy and that this can be used to enhance therapeutic outcome. The plan is to test this hypothesis in RIF-1 tumor models in mice, including the monitoring of modifications of tumor hypoxia by an innovative approach to deliver an effective vasoactive agent with maximal effectiveness and minimal toxicity (benzyl nicotinate, delivered transdermally).  Md. Nadeem Khan, Ph.D., Radiology Research Assistant Professor, is PI on this grant.

Oxygen Guided Hypofractionated Radiotherapy for Gliomas

The goal of this project, which is funded by NIH, is to demonstrate that hypofractionated radiotherapy can be significantly enhanced by irradiating at times of optimal tumor oxygenation, and that the use of hyperoxic therapies in conjunction with hypofractionated radiotherapy can be optimized by use of the information on oxygen levels in the tumors.  Md. Nadeem Khan, Ph.D., Radiology Research Assistant Professor, is PI on this grant.

Imaging the Mitochondrial Response to Neural Activity

This grant, which is to be funded by NIH, is to develop and validate spectral-domain imaging technology at visible wavelengths to collect and reconstruct 2-dimensional topographic and 3-dimensional tomographic images of the oxidation state of mitochondrial cytochrome c and cytochrome oxidase.  Roger Springett, Ph.D., Radiology Research Assistant Professor, is PI on this grant.