Research — Radiology

Interested students should contact the appropriate individual in each division regarding the types of research projects available.

Tom Conturo, MD, PhD
2nd Floor East Building, Rm 2120
Magnetic resonance (MR) imaging is a noninvasive means of providing images of the human body at high spatial resolution and contrast sensitivity. The contrast can be manipulated to depend on different properties of tissue water, enabling the study of a variety of biological processes. In some cases, endogenous or exogenous paramagnetic MR contrast agents are used to alter the MRI contrast by perturbing the tissue water environment. Recently, new MRI hardware has also enabled techniques having high temporal resolution. Using the unique contrast properties of MRI and the higher spatial/temporal resolution, non-invasive techniques can be devised to study neuronal activity, tissue perfusion, water mobility (diffusion), and neuronal fiber pathways in the human brain. The goals of Dr. Conturo’s research lab are to develop and apply MR imaging techniques for quantitative imaging of cerebral perfusion, brain function, water diffusion, and neuronal fiber pathways. These techniques utilize the MR signal effects of exogenous bolus-injected contrast agents, endogenous hemoglobin, and microscopic water diffusion. Long-term goals are to apply these methodologies toward imaging and understanding tissue structure, function, and physiology in the brain and other organs in normal and abnormal conditions. The approaches that are used in this laboratory cover a broad range of areas, including MRI physics, MRI pulse sequence development, theoretical derivations, computer simulations, image-processing, computer graphics, custom contrast agent design and syntheois, phantom studies, animal models, human studies, clinical patient studies, and comparison with other imaging modalities.

Farrokh Dehdashti, MD
Nuclear Medicine PET Facility, 10th Floor, Mallinckrodt Institute of Radiology
Positron emission tomography (PET) is an imaging technique that produces images reflective of biochemical processes of normal and abnormal tissues. PET is complementary to anatomic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). The ability of PET to quantify fundamental processes, such as blood flow, oxygen metabolism, glucose metabolism, and receptor density, makes this technique very desirable to both investigators and clinicians. Dr. Dehdashti’s research utilizes the conventional PET radiopharmaceutical, F-18 fluorodeoxyglucose (FDG), as well as a variety of unique PET radiopharmaceuticals such as Cu-64-diacetyl-bis[N4-methylthiosemicarbazone (Cu-64 ATSM), a hypoxic imaging tracer, and 18F-labeled 3′-deoxy-3’fluorothymidine (FLT), a proliferative imaging tracer. Below is a partial list of the research projects relating to PET: (1) PET assessment of progesterone receptors in patients with newly diagnosed breast cancer with a new progesterone-receptor imaging tracer, 21-[18F]Fluoro-16,17-[(R)-1’–furylmethylidene)dioxy]-19-norpregn-4-ene-3,20 dione (FFNP); (2) assessment of cell proliferation with a new tracer, N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2 (2-[18F]-fluoroethoxy)-5-methylbenzamide ([18F]3c), also called [18F]ISO-1 by imaging sigma receptors in patients with various solid cancers; (3) PET assessment of tumor hypoxia using 64Cu-ATSM in patients with cervical cancer (the major goal of this project is to predict prognosis); (4) FDG-PET/CT study in cervical cancer to evaluate the change in tumor FDG heterogeneity and SUVmax during chemoradiation and whether these changes are predictive of response to therapy; (5) PET using [18F]FHBG (9-[4-fluoro-3-hydroxymethyl-butyl]guanine), analog of Penciclovir, an acycloguanosine derivative and antiviral drug, for possible tracking of GvHD in patients who were prior recipients of unrelated allogeneic bone marrow transplant for any hematologic malignancy, (6), FLT-PET/CT to assess tumor cell proliferation in patient must have histologically or cytologically confirmed ER+ stage IV or metastatic invasive breast cancer.

Rob J. Gropler, MD
Room 1307 East Building
Cardiovascular Imaging Research. The research in the Cardiovascular Imaging Laboratory is designed to better understand the relationship between myocardial perfusion, intermediary metabolism and mechanical function in both normal and abnormal cardiac states. The research involves the integration of several imaging techniques with diverse strengths such as PET, MRI, CT and echocardiography. The success of the research requires several paths of investigation to be pursued in parallel. For example, in order to image the biologic processes of interest requires continued technical developments for each of the imaging methods listed above. There are ongoing efforts to permit more accurate PET measurements of myocardial substrate metabolism. They include the development of novel tracers of extracted substrates, the development of acquisition schemes to assess endogenous substrate metabolism, and the validation of mathematical approaches to correlate the tracer kinetics with the underlying metabolic processes. These studies are being pursued in small and large animal models and then in humans. Another example includes the current efforts to develop approaches to image the coronary arteries non-invasively by MRI using novel contrast agents and acquisition schemes. In addition, techniques are being developed to permit MR guided interventions on the coronary arteries. This undertaking includes the development of novel guide-wire tracking and catheter tracking schemes using both passive and active approaches. Finally, to permit assessments of myocardial oxygenation and thus, perfusion, techniques are being developed to permit BOLD imaging the myocardium. Another path of the research is to determine how this perfusional-metabolic-functional relation is altered by normal life changes and then determine how disease states alter the relationship. For example, both PET and echocardiography are being used to characterize the age and gender related changes on myocardial perfusion, substrate metabolism and function. To study the relationship in disease states, similar studies are being performed in patients with diabetes and obesity. A third path to determine the mechanisms responsible for these changes in this metabolic-functional relation and identify potential interventions that may reverse or ameliorate them. In this regard, similar imaging studies are being performed to determine the importance of nitric oxide and the PPARa system in defining this metabolic-functional relation.

Stephen M. Moerlein, PharmD, PhD
1st Floor East Building
Research interests lie in the general area of labeled tracer development for nuclear medicine imaging, especially positron-emission tomography (PET). Developmental effort begins with synthesis of target structures, preclinical screening that involves in vitro biochemistry and pharmacological testing, and ex vivo biodistribution studies in small animals. Promising tracers are then examined by in vivo imaging of animal subjects and tracer kinetic modeling. The final step in the transition of a radiochemical into a labeled drug takes into account radiation dosimetry, pharmaceutical quality, and the development of automated production and GMP production processes to streamline delivery to human subjects. Each of these aspects of radiopharmaceutical development are investigated, with a primary emphasis in novel agents for evaluation of pathological processes in neurology and oncology.

Marc Raichle, MD
2nd Floor East Building
We use functional imaging techniques, both positron emission tomography and functional magnetic resonance imaging, to study the normal organization of the human brain and the effect of selected diseases. The research focuses on both the methodology (imaging and experimental) and specific questions in cognitive neuroscience.