Hoby Hetherington, PhD

Research Interests

Brain; Epilepsy; Magnetic Resonance Imaging; Metabolism; Neurosurgery; Radiology; Seizures

Research Organizations

Cancer Center: Radiobiology & Radiotherapy

Research Summary

Patient-oriented epilepsy research at Yale has led to major advances in the diagnosis and treatment of epilepsy. Yale was one of the first centers in the world to perform epilepsy neurosurgery, and remains at the forefront in developing innovative brain imaging methods, deep brain stimulation, other neurosurgical techniques, medication trials, and additional novel approaches.

Specialized Terms: High field methods and hardware for magnetic resonance imaging; human brain; metabolism and dysfunction in epilepsy; magnetic resonance spectroscopic imaging

Extensive Research Description

Our group focuses on the development (hardware and software) and application of magnetic resonance spectroscopic imaging (MRSI) techniques for the evaluation of neurological disorders. MRSI allows the chemical composition of the brain, including major neurotransmitters and metabolites, to be mapped at spatial resolutions of 0.5 milliliter (approximately a cube of 1/3 of an inch) or better. These measurements allow us to evaluate the biochemical status of the brain, including: 1) how well neurons are functioning; 2) the extent to which energy production in the brain meets demand; and 3) levels of the primary inhibitory and excitatory neurotransmitters. Although we have worked in a variety of areas (Alzheimer’s, Multiple Sclerosis, Migraine, Addiction) our work currently focuses in two main areas: Epilepsy and Brain Tumors, with minor projects in Schizophrenia and Parkinson’s.

All of our human work is performed at 7T, of which approximately 25 system exist world wide. Spectroscopic studies are typically limited by SNR; however with increasing field strength, the SNR grows at least linearly. Unfortunately, power deposition grows by the second to the third power of the field strength, making conventional lower field (3T) spectroscopy methods unfeasible at 7T due to excessive tissue heating. Further due to tissue RF field interactions the homogeneity of conventional RF detectors degrades substantially resulting in a factor of two in inhomogeneity across objects the size of the human head. Finally the static magnetic field inhomogeneity grows linearly with field strength, degrading spectral resolution. To overcome these limitations the more technical components of our work focus on four areas: 1) the development of new multi channel (“transceiver”) RF arrays which improve homogeneity and decrease power deposition; 2) the development of specialized hardware and software for ultra high magnetic field homogeneity within the brain; 3) and pulse sequences which utilize RF shimming concepts to provide anatomical localization with out the use of gradients thereby minimizing power deposition and eliminating chemical shift dispersion errors and 4) pulse sequences to acquire measurements of a variety of metabolites including NAA, glutamate and GABA.

Although there has been significant advances in the development of new drugs to treat epilepsy, about 1/3 of all people who have epilepsy continue to experience seizures. These seizures have a significant impact resulting in shortened life spans, a much higher incidence of psychiatric disorders, and, on a personal level, increased incidences of divorce, loss of jobs and revocation of driving privileges. In these subjects, surgery can provide an alternative when the location within the brain giving rise to the seizures can be identified. In neocortical epilepsy, surgical treatment is typically only successful in ½ of the patients due to the limitations of conventional imaging methods in finding the origin of the seizures. In many other patients a failure to localize the seizures or their proximity to areas of key brain function preclude surgery as a treatment option. In epilepsy our work includes two main areas: 1) the application of MRSI to identify where seizures originate from for the purposes of surgical planning and 2) to better understand the biochemical changes associated with epilepsy so as to develop alternative methods for the medical treatment of seizures for patients in which surgery is not an option.

Brain cancer remains amongst the most difficult to treat of all forms of human cancer. Although there has been significant progress in the development of new agents and the use of focused radiation to treat brain tumors, results vary dramatically amongst individuals. For this reason, monitoring of the effects of treatment are critical in determining the course of therapy, balancing treatment of the tumor versus damage caused to the brain due to the toxicity of the agents and approaches used. Unfortunately, conventional imaging methods (MRI and PET) can not discriminate the effects of radiation and chemotherapy from tumor regrowth during the first few months of therapy, delaying optimal therapy. Failure to treat tumor regrowth quickly results in poorer outcomes and tumor control, while additional courses of radiation and chemotherapy result in significant brain damage and loss of function. Our work is focused on using MRSI methods to resolve between tumor regrowth and brain injury due to therapy, using characteristic changes in tissue energy production seen in radiation injury. By resolving tumor regrowth from radiation and chemotherapy injury we will be able to more optimally manage treatment, using additional radiation treatments or other chemotherapeutic agents for tumor regrowth, or giving steroids to treat brain injury due to therapy.

Development of Magnetic Resonance Spectroscopic Imaging (MRSI) methods to evaluate the metabolic effects of seizures for improving presurgical localization and medical treatment.
Development of MRSI methods for the evaluation of the response of tumors to treatment.
Development of multichannel RF coil technologies for high field human brain imaging.
Development of software and hardware for improved B0 shimming for high field human brain imaging.

Selected Publications

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Contact Info

Hoby Hetherington, PhD
Mailing Address
NeurosurgeryPO Box 208082
New Haven, CT 06520-8082