2020 Distinguished Investigators2020-07-02T16:33:06-04:00

2020 Distinguished Investigators

Eric T. AhrensAhrens’ 26-year research career involves MRI/NMR innovation and focuses on adapting these methods to visualize molecular and cellular events in vivo. Ahrens is engaged in the design, characterization and application of novel contrast agents for fluorine-19 cell tracking and visualizing gene expression using MRI. He has pioneered the use of fluorine-19 probes for clinical cell tracking. He has published over 100 articles and is an inventor on 11 patents. Funding to support Ahrens’ research laboratory has totaled over $27M, including a 6-year $6.4M CIRM Leadership Award and 6 NIH RO1’s as PI.
Jyrki Ahveninen, PhDDr. Ahveninen has pioneered multimodal neuroimaging studies of human auditory cognition. His fMRI-guided MEG source modeling studies provide evidence of parallel “what” and “where” processing pathways of human auditory cortex whose feature sensitivity is modulated by selective attention, based on a mechanism that not only increases the gain but also changes the population tuning of neurons. Dr. Ahveninen causally verified the existence of such parallel “what” and “where” pathways by inducing “transient lesions” in human auditory cortex by using MRI-guided TMS.
David A. Bluemke, MD, PhDSome of Dr. Bluemke’s key scientific contributions include; Evaluation of left ventricular structure and function by MRI. As the imaging principal investigator in the MESA, EDIC, ARVC/D and other multi-center NIH studies, Dr. Bluemke was responsible for the largest existing databases of structural information of the heart, resulting in hundreds of publications establishing MRI as a standard of reference, as well as establishing international MRI diagnostic criteria for ARVC/D. Novel innovation and development of methods to evaluate myocardial tissue composition and fibrosis using MRI and CT and the development of photon counting CT technology with demonstration of first in human use of this technology.
Giorgio Bonmassar, PhDThe unifying theme of Dr. Bonmassar’s academic career has been the development and pre-clinical testing of novel methods for performing MRI/CT compatible electrophysiological measurements and stimulations. He developed an innovative therapeutic stimulation, the micro-magnetic stimulation for MRI compatible stimulation, and was the first author in Nature Communications. He also invented and published as a senior author in Nature Scientific Reports a new type of wire, invisible to electromagnetic fields, making possible safe MRI scans of patients with DBS. Finally, Dr. Bonmassar invented and was the senior author in Radiology of an “MRI/CT-invisible” and flexible ECoG, for simultaneous fMRI measurement during neuro-stimulation.
Michelle S. Bradbury, Md, PhDWhile the potential for advances in nanotechnology to contribute to improved healthcare has been discussed, very few have transferred completely new nanotechnologies into clinical trial. Dr. Bradbury has made incredible strides in this arena including; the landmark Phase 1 first-in-human study “Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe” that highlighted such an achievement in melanoma patients. A second important contribution from Dr. Bradbury is the “Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer”, which demonstrates a first-in-kind particle design combining the specificity of antibodies with favorable particle biodistribution and renal clearance profiles. Finally, a third important contribution showed, for the first time, in unique self-therapeutic properties of ultrasmall silica nanoparticles, which induce and iron-driven cell death program, ferroptosis, in vivo without the need for cytotoxic drug.
Deborah Burstein, PhDDr. Burstein’s career has encompassed several foundational studies in MRI. Among them, she determined the tissue NMR characteristics of sodium, laying the groundwork for the interpretation of sodium MRI. She developed coronary artery imaging in small animals, with systematic technique development for transfer to clinical coronary imaging. She established a novel approach for molecular imaging of cartilage; the technique (“dGEMRIC”), has been extensively applied in clinical trials. These experiences have led to new methodologies for research training, and, how to consider and design research projects to put them on an optimal path to impact.
David Cormode, PhDThe Cormode Lab’s research focuses on the development of novel and multifunctional nanoparticle contrast agents for medical imaging applications. A current major area is the development of gold and bismuth nanoparticles as contrast agents for computed tomography (CT). The nanoparticles can be further modified to have a variety of additional functional properties, such as fluorescence, MRI contrast or therapeutic effects. Related areas of interest are novel computed tomography-based imaging methods, such as dual energy CT, spectral CT and iterative image reconstruction. These technologies are being applied for structural imaging and molecular imaging of the levels of specific cell types and proteins in vivo. These approaches provide enhanced characterization of cardiovascular diseases and cancers, which should allow improved selection of therapies and monitoring of response to treatments.
E. James Delikatny, PhDSome of Dr. Delikatny key research contributions include; the development of MR spectroscopy to monitor lipid metabolism during tumor development and therapy response in cancer models and human tissue, the synthesis of NIR imaging probes for non-invasive detection of lipid enzyme expression and activity. Finally, the translation to intraoperative NIR imaging for detection of tumor margins in patient canines with lung cancer and the development of Cerenkov imaging, including synthesis of functional contrast agents to detect pH and redox status.
Sharmila Dorbala, MD, MPH,Dr. Dorbala is an accomplished investigator with a substantial and ongoing research program. Her seminal scientific contributions to molecular imaging of cardiac amyloidosis (CA) have transformed its management. She discovered that F-18 Florbetapir can accurately image CA through specific binding to amyloid deposits – introduced the first radiotracer for k: liagnosing light-chain CA. By accurate detection of visceral (Article #19) and pulmonary AL amyloid, her work paved the way to estimate whole-body amyloid load. Identification of preclinical light-chain CA, prior to overt phenotypic thanges on MRI or echocardiography, has made possible early and effective therapy.
Jiang Du, PhDDr. Du formed the UTE Lab in 2005 to develop morphological and quantitative UTE techniques to evaluate short T2 tissues such as bone, menisci, ligaments, tendons, and myelin, which are all “invisible” with conventional clinical MR sequences. These techniques have allowed quantitative evaluation of cortical and trabecular bone, including their major components including pore water content (a biomarker of bone porosity), bound water content (a biomarker of organic matrix density), collagen backbone proton content (a biomarker of organic matrix density), bone susceptibility (a biomarker of bone mineral density), thus a comprehensive assessment of osteoporosis (OP).
These techniques have allowed quantitative evaluation of all major knee joint tissues (e.g., superficial and deep layers of articular cartilage, calcified cartilage, subchondral bone, menisci, ligaments, tendons) and their components (e.g., proteoglycan through UTE T1rho mapping, collagen through UTE magnetization transfer imaging and modeling, as well as bound and free water fractions and contents through UTE bi-component analysis), thus a truly “whole-organ disease” approach for osteoarthritis (OA).
Daniel Bruce Ennis, PhDFor twenty years Dr. Ennis has developed advanced cardiac and cardiovascular MRI techniques to characterize structure, function, flow, and remodeling. He is a recognized leader in quantitative cardiac MRI. His early work focused on quantitative cardiac MRI methods to assess systolic and diastolic function in patients with hypertrophic cardiomyopathy and award-winning error correction methods for flow imaging. Dr. Ennis also focuses on numerically optimizing MRI pulse sequences to enable fastest-possible scanning or mitigate measurement errors. His recent optimization work enables the acquisition of in vivo diffusion tensor images in the heart, thereby permitting direct cardiac microstructural imaging.
Frederick H. Epstein, PhDDr. Epstein’s work focuses on developing and applying MRI techniques for assessing the structure, function, perfusion, and molecular/cellular properties in cardiovascular disease. He has led the development and application of cine displacement-encoded imaging using stimulated echoes (cine DENSE) for cardiac strain imaging, developing: time-resolved multiphasic (cine) acquisition strategies for DENSE imaging of the heart; image analysis algorithms for rapidly and accurately computing displacement and strain data from cine DENSE images; 2D and 3D spiral cine DENSE pulse sequences for improved signal-to-noise ratio and coverage of the heart; and d) estimations of left‐ventricular mechanical activation delays in heart failure CRT patients. He has also used MRI for assessing myocardial perfusion, developing a hybrid gradient-echo/echo-planar first-pass MRI perfusion pulse sequence as well as image reconstruction methods, using parallel imaging, motion compensation, and low rank to accelerate first-pass MRI, and demonstrated the value of quantifying perfusion in patients with ischemic heart disease to detect impaired perfusion reserve in patients with coronary microvascular disease. He had a primary Radiology research faculty appointment for 11 years before becoming BME chair.
Michael Evans, PhDDr. Evans is a pioneer bridging the gap between chemical biology and nuclear medicine. From this position, he is internationally recognized for developing a new class of radiopharmaceuticals that selectively measure the activity of central oncogenes, including the androgen receptor, c-MYC, mTORC1, and KRAS. Preclinical and clinical trials using these technologies have revealed new insights about the pathobiology of cancer and neoplastic disorders (lymphangioleiomyomatosis), including the molecular basis of response (or resistance) to treatment. He also developed creative chemical strategies to image notoriously elusive biological targets, notably the labile iron pool (attached) and the glucocorticoid receptor.
Joel Garland Fletcher, MDDr. Fletcher is a world leader in diagnostic CT and the imaging of Crohn’s disease. He is known for his leadership of interdisciplinary teams (physicists, radiologists, clinicians) to develop and validate new imaging methods, with an aim towards translating technologies into clinical practice. In CT imaging he has partnered with Dr. Cynthia McCollough and others to develop new diagnostic tasks in CT and radiation dose reduction technologies. In Crohn’s imaging, he has partnered with Dr. David Bruining to develop cross sectional imaging of the small bowel and understand the impact of using imaging endpoints to guide clinical decision making.
Ajay Gupta, MD, MSAcross the various neurological disorders which have been the focus Dr. Gupta’s research, the two unifying methodologic themes have been the formal quantification of the value and accuracy of diagnostic imaging; and assessment of emerging neuroimaging technologies with the goal of translation to “real-world” clinical practice. Within this broader conceptual framework, his major contributions have been in two major specific areas of interest: 1) developing novel imaging techniques to aid in prevention of stroke and 2) validating emerging techniques to image brain inflammation in various neurological disorders, including multiple sclerosis and, most recently, neurodegenerative diseases.
David Brian Hackney, MDSome of Dr. Hackney’s contributions to our understanding of MR imaging of white matter, particularly the axonal components have been highlighted. These were motivated by an interest in spinal cord injury (SCI) and include; Fiber orientation determined diffusion anisotropy in developing cranial nerves, Employed diffusion imaging to assess the effects of therapies that preserve axons or promote regeneration after, Development of an image-based finite difference model for simulating restricted diffusion, Employment of q-space imaging to determine the distribution of axon fiber diameters in rat spinal cord white matter and helped determine the effects of motion on in vivo human spinal cord diffusion imaging.
Tamara G. Hershey, PhDDr. Hershey’s work is in the fields of cognitive and clinical neuroscience. Her lab uses a wide range of neuroimaging, pharmacological and cognitive techniques to understand the impact of metabolic a neurodegenerative condition on the brain across the lifespan. Key accomplishments include defining the neural underpinnings of cognitive and mood dysfunction in disorders relevant the basal ganglia, highlighting the effects of diabetes and obesity on the brain, particularly within development, and determining the neurodevelopmental and neurodegenerative impact of a rare genetic condition, Wolfram Syndrome.
Christopher P. Hess, MD, PhDDr. Hess has made numerous important scientific contributions. First, he has pioneered the development of advanced MRI techniques, especially in diffusion, and their application to clinical practice. In the 1990s, he proposed the first clinically feasible high angular resolution approach to diffusion imaging and tractography which is now used widely for neurosurgical planning, modeling white matter structure, and evaluating structural connectivity. Second, his work studying congenital arteriopathy and general imaging of neurovascular disease is highly cited. Third, he contributed to the development of several new imaging markers of disease, including 7T MRI in neurodegeneration and neuro-oncology and connectivity in the neonatal brain.
Jacob M. Hooker, PhDDr. Hooker is co-senior author of the first demonstration that a transition metal complex could essentially ‘switch’ the way fluoride behaves in chemical reactions. This innovation and those that have followed from his lab have fundamentally changed the landscape for PET radiotracer development. Dr. Hooker developed the first tools for studying gene regulation in the living human brain by designing imaging agents targeting epigenetic enzymes. He has used these tools to measure epigenetic relationships to age and sex.
Kayvan R. Keshari, PhDThe focus of Dr. Keshari’s research is in the development and application of metabolic imaging strategies to interrogate cancer metabolism in vivo. His recent work has created platforms to study metabolism, developed novel hyperpolarzied probes to characterize metabolic flux in oncogentically driven pathways and translate hyperpolarized MRI to humans.
Duong-Hyun Kim, PhDDr. Kim’s research has been focused on biomaterials for image guided medicine. His research experience is very interdisciplinary, and he has studied image guided therapy using multifunctional nanoparticle platforms to treat cancers for 18 years and published over 80 papers on international refereed journals. One of his researches is a new novel magneto-mechanical cancer therapy using MRI visible magnetic discs (in Argonne National Laboratory collaborating with U of Chicago Medical School). The results had been published as a cover page in “Nature Materials” and featured as major news and discussed in cancer related forum websites (ACS and NCI). Now he is the director of Biomaterials for Image Guided Medicine (BIGMed) lab and working closely with clinicians, medical scientists, biologist and imaging professionals to translate new cancer therapeutic approaches to the clinics. As a result of these collaborative works, he has multiple ongoing and completed NIH research projects and published papers focusing on image guided medicine in high impact journals.
Gerald M. Kolodny, MDDr. Kolodny has made seminal research contributions. He was the first to show that the pattern of protein synthesis in the cell changes during the cell cycle that macromolecules can be transferred between cells and that cells contain a large array of small RNA species which are now known to perform very specific intracellular functions. Using PET/CT Dr. Kolodny’s group in endocrinology nuclear medicine showed that brown fat is present in adult humans. By suppressing normal myocardial uptake on PET/CT scans they were able to demonstrate that PET/CT could be used to identify inflammatory plaque in the coronary arteries.
Despina Kontos, PhDDr. Kontos’ research focuses on developing computational methods for advancing the use of imaging as a biomarker for precision cancer screening, prognostication, and treatment. She has shown that imaging phenotypes of parenchymal complexity independently relate to breast cancer risk. Dr. Kontos was also among the first to show that tumor imaging phenotypes correlate to prognostic gene expression profiles and can independently predict long-term recurrence. Overall, her research has moved the field forward by transitioning radiologic evaluation from visual inspection to reproducible quantitative phenotypic signatures with prognostic and predictive value.
Ronilda Lacson, MD, PhD Dr. Lacson’s seminal scientific contributions include investigating and rectifying diagnostic process failures utilizing various data sources and events (e.g. from a safety reporting system), within a Human Factors framework. She worked with the department to implement and evaluate systems-based approaches including optimizing communication of critical test results. Recent pioneering work demonstrated that the computerized physician order entry system was an under-recognized source of diagnostic imaging care plan execution failures, where orders were frequently left unscheduled. Dr. Lacson has also raised awareness for social determinants of health, such as Hispanic ethnicity, that are contributory to suboptimal follow-up with safety initiatives to address them ongoing.
Deborah Levine, MDDr. Levine has made many important scientific contributions including; the benign nature of simple adnexal cysts – Dr. Levine showed that cysts are common in postmenopausal women, and that the majority of them change over time, getting smaller as well as larger. These cysts don’t need to be surgically removed. Fast MRI for assessment of the fetus – She has over 80 publications in the field of obstetric MR for improved care of fetal/maternal dyad. This has dramatically changed fetal and maternal imaging in pregnancy. Finally, her recent focus has been on multi-institutional multi-subspecialty collaborative efforts and she has authored 36 guidelines, 9 consensus conferences and 13 publications on improving scientific publications.
Yongjian Liu, PhDDr. Liu’s research has focused on the development and translation of novel molecular probes from preclinical research to human PET imaging and therapy with a focus on cardiovascular research. He has been working on agents with various imaging characteristics including peptides, small molecules, antibodies and nanoparticles to study the pathogenesis, progression/regression, and treatment response in a number of animal models. Dr. Liu has translated four radiotracers for human PET imaging including two antibodies, one nanoparticle and one peptide tracer for human imaging.
Caterina Mainero, MD, PhDDr. Mainero has performed pioneering work on imaging cortical lesions in patients with multiple sclerosis (MS). Cortical lesions represent a major contributor of MS disease progression and, though extensively described in postmortem studies, are usually undetected in clinic. Dr. Mainero’s group was the first to image and characterize in vivo, using ultra-high field 7-Tesla MRI, the different types of cortical MS lesions described by neuropathology, to provide insights into their pathogenesis by demonstrating that cortical lesions develop mostly within cortical sulci and in iuxtameningeal cortical layers, and to report associations of cortical lesion load assessed at 7-Tesla with neurological outcome.
David J. Marcinek, PhDDr. Marcinek’s most important research contribution has been the development and application of non-invasive tools to assess skeletal muscle mitochondrial function in human and preclinical models of disease. This approach combines 31P MRS and optical spectroscopy to measure metabolic fluxes in vivo. His work has demonstrated that combining these in vivo tools with cell and biochemical approaches provides important new insights into the role of mitochondria in chronic disease. Dr. Marcinek is applying these tools to as a Project Leader in a P01 using rodent models and as the UW PI as part of a multi-institution R01examining aging human subjects.
Zdravka Medarova, PhDDr. Medarova’s contributions relate to the development of image-guided RNAi cancer therapies. Her earliest paper on this topic has been cited over 700 times. Since then, she has published over 20 papers in this area and has obtained three patents. A second direction focuses on the imaging of prostatic zinc content. This work was featured in Science Magazine’s Editor’s choice and has resulted in one patent. An additional contribution involves the profiling of miRNA expression in intact cells and live animals. This work has resulted in two patents.
Scott D. Metzler, PhDDr. Metzler’s most important research contributions have been in the
area of SPECT imaging with an emphasis on quantitative imaging from theoretical analysis to hardware implementation. He has developed and validated analytic models of various collimators, but particularly pinhole and slit-slat. Dr. Metzler has developed calibration techniques for applying those models to real-world systems, including a novel helical-orbit pinhole system for addressing sampling completeness, an adaptive pinhole-collimator system for small-animal dynamic cardiac imaging, and the C-SPECT scanner, which is currently under development for dedicated human cardiac SPECT perfusion and dynamic imaging.
Vivek Prabhakaran, MD, PhDDr. Prabhakaran has made important scientific contributions in three key areas: Clinical fMRI/DTI for presurgical planning, Connectome – resting state fMRI methodology and its utilization in aging and patient populations, and Brain Computer Interface technology for stroke rehabilitation. Dr. Prabhakaran has published a series of papers e.g. in AJNR, Neuroimage, Interdisciplinary Neurosurgery in which he has examined the utilization of Clinical fMRI & DTI for pretreatment planning of brain tumor, epilepsy, and vascular lesion patients and its impact on patient outcomes. NIH launched a connectome initiative, which has led to a major change in the field of imaging, specifically connectome imaging, he has received several NIH connectome grants. Dr. Prabhakaran has also been a major contributor to the field of Brain Computer Interface Technology and its utilization for stroke rehabilitation. His work has been featured in numerous media outlets.
Vijay Sharma, PhDDr. Sharma, a lead inventor of 5 US patents, deploys state-of-the art tools to design, validate, and translate molecularly specific PET tracers for biomedical imaging. Some key examples include; imaging coronary artery disease chemotherapy-induced cardiomyopathy to allow stratification of chemotherapeutic choices, and diffuse and fibrillary AB to detect prodromal stages of Alzheimer’s disease. While 2 NIH-funded human studies (CAD and AD) are underway, successful accomplishment of his programmatic mission would deliver noninvasive tools for interrogating pathophysiology of different diseases and integrating precision imaging.
Leslee J. Shaw, PhDDr. Shaw is a leading cardiovascular outcomes researcher whose major focus in the quality and effectiveness in the clinical diagnosis and imaging of ischemic heart disease. She has published more than 700 publications and presented more than 300 abstracts in major scientific meetings in the United States, Europe, Asia, and South America. She has been ranked for more than a decade as one of the top 1% of clinical researchers with the most highly cited publications.
H. Tom Soh, PhDDr. Soh’s laboratory develops advanced biosensors that can achieve rapid, sensitive, specific, and multiplexed molecular measurements in complex clinical samples. His lab invented the “Real-time biosensor” technology for continuously measuring specific biomolecules in live subjects in vivo
These biosensors require synthetic antibodies (aptamers) that change their conformation upon target binding. To create these reagents, Dr. Soh’s lab has developed many foundational technologies for high-throughput screening including the “Particle Display” technique and invented methods for controlling their thermodynamics and kinetics.
Konstantin V. Sokolov, PhDDr. Sokolov is a pioneer in molecular cancer imaging using gold and multi-modal magneto-plasmonic nanoparticles — a seminal paper in Cancer Research, 2003. He has also pioneered exogenous agents for molecular photoacoustic imaging and demonstrated unprecedented sensitivity of ca.
Hemant D. Tagare, PhDDr. Tagare has made a number of significant contributions in image processing of bio-medical images. He has proposed a methodology for medical image databases where images can be recovered based on their content. He developed the mathematics and numerical methods for a new generation of non-rigid image registration and image correspondence algorithms. He developed robust image segmentation algorithms for segmenting cardiac ultrasound images using machine learning and optimization methods. He developed advanced methods for tomographic reconstruction that are used in the new field of cryogenic electron-microscopy to create three dimensional structures of individual molecules. Recently, Dr. Tagare has been using machine learning methods to develop longitudinal disease progression models for Parkinson’s disease using DaTscan images.
Martin Torriani, MD, MMScDr. Torriani pioneered proton magnetic resonance spectroscopy for examining lipid content in muscle, liver and bone marrow in conditions ranging from anorexia nervosa, obesity and HIV-lipodystrophy. Dr. Torriani was the first to describe the hip abnormality he coined as ischiofemoral impingement, and described a novel knee friction syndrome, posteromedial knee friction syndrome. Further, Dr. Torriani pioneered the use of ultrasound-guided injections of botulinum toxin for diagnosis and treatment of patients suffering from neurogenic thoracic outlet syndrome. Dr. Torriani also described novel adipose tissue phenotypes in HIV.
Eric C. Wong, MD, PhDDr. Wong and colleagues published the first paper on human BOLD fMRI, and introduced correlation analysis in fMRI. The bulk of his research has been in the development of Arterial Spin Labeling (ASL) technology. He led an international effort to standardize clinical ASL for the first time, and in 2015 was the lead and corresponding author of the paper that summarized these efforts. He introduced velocity selective ASL for CBF mapping in stroke, and vessel encoded ASL for mapping of vascular territories, which are in clinical translation and are likely to become future standards.