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Biomedical Engineering Research

Biomedical engineering research at Thayer School is distinguished by its strong alliance with both Dartmouth Medical School (DMS) and nearby Dartmouth-Hitchcock Medical Center (DHMC), one of the few academic medical centers in the nation which serves a largely rural area.

Medical Imaging

The imaging groups at Thayer School are developing four new model-based modalities for breast cancer detection and other biomedical applications. (See Alternative Breast Imaging: Four Model-Based Approaches edited by Professors Paulsen and Meaney.)

Near-infrared imaging (NIR) provides a way to quantify blood and water concentrations in tissue, as well as structural and functional parameters. Since normal tissue, benign tumors, and malignant tumors each carry different concentrations of both hemoglobin and water, and have different levels of oxygen demand and ultrastructural scattering, NIR spectroscopy can be combined into standard imaging systems as an effective method of to provide additional information for breast cancer detection and diagnosis. Work is ongoing to improve techniques for better image reconstruction, display and integration with magnetic resonance imaging (MRI) and computed tomography (CT) imaging.
See also Near Infrared Imaging Group
(Faculty contacts: Pogue, Paulsen, Jiang)

Electrical bioimpedance measurements of tissue provide significant levels of contrast between benign and malignant pathologies due to the vastly different morphologies occurring between tissue types. Focal sensing or mapping of these properties can provide clinicians useful information regarding the extent and severity of diseases like cancer. Our group is currently developing technologies to couple bioimpedance sensors to clinical devices including: 1) intraoperative instruments for use in assessing surgical margins during tumor resection; and 2) standard biopsy needles for use in providing real-time pathological assessment of tissue.
(Faculty contact: Halter)

Electrical impedance imaging for breast cancer screening is the process of imaging the electrical property (conductivity and permitivity) of tissue using electrodes located on the body surface. This project is one branch of the larger effort to develop innovative technologies for breast cancer detection.
(Faculty contacts: Hartov, Borsic, Halter)

Electrical impedance imaging for prostate cancer screening is the process of imaging non-invasively the electrical properties (conductivity and permittivity) of the prostate and its vicinity using electrodes mounted onto an intracavitary probe.
(Faculty contacts: Hartov, Borsic, Halter)

Magnetic resonance elastography is being developed as a technique to measure the elasticity of tissue in vivo by gently shaking the tissue in a magnetic resonance imager. The displacements measured are used to determine tissue mechanical properties which can help identify and classify breast lesions. See also Discovering at Thayer School.
(Faculty contacts: Paulsen, Weaver)

Microwave imaging spectroscopy (also commonly referred to as microwave computed tomography) presents the challenge of measuring the signal data necessary to produce meaningful images. Development of site-specific antenna arrays along with improved electronic signal detection technology is rapidly making this measurement feasible for breast cancer detection. A second-generation tomographic breast imaging system has been completed and the data are being used to recover permittivity and conductivity maps of the breast for evaluation by a clinician.
(Faculty contacts: Meaney, Paulsen)

Emerging Imaging Modalities

Medical Therapy & Intervention

Enzyme therapeutics are a potential means of addressing the emerging health care crisis resulting from drug resistant microbial pathogens. Efforts are focused on the redesign of antimicrobial proteins for enhanced bactericidal activity towards various clinically relevant targets. One facet of this work relates to complications associated with the genetic disease cystic fibrosis, and is being investigated in conjunction with the Cystic Fibrosis Foundation Research Development Program at Dartmouth Medical School.
(Faculty contact: Griswold)

Fluorescence-guided neurosurgery is important for the resection of some types of cancerous tumors where the tumor and normal tissue are similar in appearance and texture, and patient prognosis depends heavily on the completeness of resection. By selectively tagging tumor tissue with fluorescent dies, it becomes possible to visually discriminate between normal and tumor tissues and improve significantly the completeness of tumor resection.
(Faculty contact: Paulsen, Pogue, Hartov, Leblond, Ji)

Hyperthermia—selectively elevating the temperature of body tissue—has a variety of therapeutic effects. Different methods of microwave heating are being developed for use in cornea reshaping, fallopian tube occlusion, and treatment of benign prostatic hyperplasia as well as liver and prostate cancer.
(Faculty contact: Trembly)

Iron nanoparticles for magnetic hyperthermia are being developed for cancer treatment. An iron oxide coating is used for either localized magnetic hyperthermia or as a thermal trigger for drugs delivered in vesicles. Localized nanoparticles enable magnetic hyperthermia to treat the tumor with minimal damage to surrounding healthy tissue. Optimization of heating mechanisms (maximum heat rise per unit weight of particles) will allow either smaller tumors to be targeted (possibly even metastases) or a smaller concentration of nanoparticles to be used (thereby minimizing toxic effects), or both.
(Faculty contacts: I. Baker, Hoopes)

Photodynamic therapy (PDT) is a newly emerging therapy for displastic tissues, such as cancer, age-related blindness, pre-malignant transformation or psoriasis. The therapy involves the administration of a photosensitizing agent, together with the application of moderate intensity light to active the molecules to produce local doses of singlet oxygen. Ongoing research topics include, developing improved dosimetry instrumentation and software, fluorescence tomography imaging to sense drug localization, and assaying unique tumor biology and treatment effects in experimental cancers.
(Faculty contacts: Pogue, Hoopes)

Functional biomarkers for Alzheimer's Disease (AD) are needed for diagnostic purposes and as measures of efficacy as new drugs enter clinical trials. Concurrent measurements with electroencephalography and near-infrared spectroscopy in humans enable time-series analysis neurovascular coupling to reveal physiologic abnormalities that can serve as functional biomarkers of early AD.
(Faculty contact: Diamond)

Therapeutic protein engineering involves: 1) advancing technological solutions for the safe, fast, and cost-effective mass-production of fully-humanized proteins used in drug discovery and development; and 2) developing enzyme therapeutics for treatment of complications associated with the genetic disease cystic fibrosis. See also Chemical and Biochemical Engineering Research
(Faculty contacts: Gerngross, Griswold)

Non-linear Image Reconstruction

Implementation of non-linear image reconstruction techniques is at the core of the medical imaging projects. Excitation-induced measurements from each instrument are compared with calculations from corresponding numerical models to compute updated property images of the biological target. As the images are progressively updated (or refined) in a non-linear iterative process, important features and functional information related to the objects physiological status—tumor, benign tissue, etc.—become more apparent. The computational core of the breast imaging project works synergistically with all four groups to improve our fundamental understanding of these mathematical systems to improve overall image quality and resolution. These processes have been developed for both 2D and 3D geometries in each modality and are being expanded to exploit emerging parallel computing capabilities.
(Faculty contacts: Paulsen, Meaney)

Dynamic Multimodal Imaging (DMI) is a framework of physiological models and solvers for reconstructing images of neural and vascular dynamics in the human brain. DMI combines concurrently recorded data from multiple imaging modalities such as electroencephalography, near-infrared spectroscopy, and functional magnetic resonance imaging.
(Faculty contact: Diamond)

Biological Response & Disease Modeling

Tumor pathophysiologic analysis and modeling is being carried out to examine and understand the vascular, oxygenation, and growth changes which occur in response to photodynamic therapy and radiation.
(Faculty contact: Pogue)

Dielectric properties of tissue—measured through advanced microwave imaging techniques—convey functional information useful for making clinical diagnoses. The properties reflect tissue composition of fat, bone, water, proteins, etc., and often have unique spectral characteristics. The relative proportions and dynamic aspects of these constituents can have important implications for breast cancer imaging, osteoporosis detection, brain imaging, and heat therapy monitoring.
(Faculty contact: Meaney)

Image-guided neurosurgery gives the surgeon the ability to track instruments in reference to subsurface anatomical structures. Using clinical brain displacement data, a computational technique is being developed to model the brain deformation that typically occurs during neurosurgery. The resulting deformation predictions are then used to update the patient's preoperative magnetic resonance images seen by the surgeon during the procedure.
(Faculty contacts: Paulsen, Hartov, Ji)

Traumatic brain injury in college athletes is being studied using finite element method to simulate brain mechanical response subject to the on-field head impact biomechanics of helmeted collegiate athletes. The predicted distributions of stress and strain are correlated with the degree of altered white matter integrity quantified using diffusion tensor imaging to investigate the mechanisms of concussion/mild traumatic brain injury.
(Faculty contact: Ji)

Biomaterials, Biomechanics & Orthopaedics

Joint replacement technology research is conducted within the Dartmouth Biomedical Engineering Center for Orthopaedics (DBEC). Founded at Thayer School in 1976, DBEC is the largest joint implant retrieval program of its type in the country and, with over 9000 specimens, has the biggest collection of retrieved joint implants in the world. Since the inception of this program—in affiliation with Dartmouth-Hitchcock Medical Center (DHMC)—Thayer School researchers have systematically identified and solved most problems related to joint replacement production, design, and materials.

Remaining issues and current foci of the program include:

determination of the rate of oxidation in vivo of polyethylene subjected to new sterilization techniques
performance of new crosslinked polyethylene materials
wear of new metal-on-metal and ceramic-on-ceramic technologies

(Faculty contacts: Collier, Van Citters)

Cell interaction with forces due to flow and electric fields has physiological implications relevant to the understanding of disease. For example, flow-induced deformation may limit cell adhesion to the blood vessel wall and thus influence inflammatory response or tumor metastasis. Our research develops physical models to elucidate universal features of cell response, mediated by the plasma membrane, to external forces. Current projects include cell electro-deformation and cell dynamics in capillary flows.
(Faculty contact: Vlahovska)

Biomechanics of abdominal aortic aneurysm (AAA) is being studied by another combination research team from Thayer School, Dartmouth Medical School (DMS), and Dartmouth Hitchcock Medical Center (DHMC). AAA is a disease in which the abdominal aorta dilates and will eventually rupture if corrective surgery is not performed in time. The cross-campus group is studying the biomechanical cause of the ruptures. The results are being used to develop a stress-based prediction of an aneurysm's susceptibility to rupture.
(Faculty contact: Kennedy)

Bioelectromagnetics & Instrumentation

Electromagnetic energy is used in a variety of ways for its therapeutic effects (see Hyperthermia). Specifically designed microwave applicators and antennae are being developed for use in cornea reshaping, fallopian tube occlusion, and treatment of benign prostatic hyperplasia as well as liver and prostate cancer.
(Faculty contact: Trembly)

Microwave electronics capable of fast data acquisition (approaching real-time) are being developed for brain imaging applications. Also, site-specific antenna arrays for microwave imaging are in development for heel imaging (screening for osteoporosis) and for brain imaging applications.
(Faculty contact: Meaney)

Clinical optical-electric probes are being developed for noninvasive simultaneous measurement of blood oxygenation and electrical potential changes associated with brain activity.
(Faculty contact: Diamond)

Neurophysiology & Modeling

Models of cerebral circulation, gas exchange and regulatory physiology are increasingly important tools for the interpretation of neuroimaging data. For instance, biophysical models can describe dynamic cerebral autoregulation (CA), which maintains relatively constant cerebral blood flow despite changes in arterial blood pressure. Medical images that spatially map CA function could provide important new information to improve treatment decisions for patients with traumatic brain injury (TBI). Better models of the background physiological fluctuations in neuroimaging data can also help to isolate the functional hemodynamic response to brain activity.
(Faculty contact: Diamond)

Neurovascular coupling refers to the mechanisms that relate evoked neural activity to localized responses by the cerebral vasculature. Better models of this coupling are needed to improve the interpretation of neuroimaging studies and understanding of neurodegenerative disease.
(Faculty contact: Diamond)

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