2008 MIPS Molecular Imaging Seminar Series

Seminar 4:30 − 5:15 pm
Discussion 5:15 − 5:30 pm

January 14, 2008

Harrison H. Barrett, PhD
Vice Chair, Radiology
Regents Prof., Radiology
University of Arizona

A unified approach to adaptive and multimodality imaging: Acquisition hardware, statistical theory and objective assessment

Multimodality imaging, which provides complementary anatomical and functional information, is very valuable in clinical and biomedical applications. Adaptive imaging, in which a system autonomously alters its configuration or acquisition protocol in response to image information from a particular subject, is in a much earlier stage of development, but it has the potential to provide a further improvement in patient care and biomedical research. This presentation will explore some of the connections between multimodality and adaptive imaging. A common theoretical framework will be presented, relevant statistical issues will be introduced, and recent progress towards implementation of adaptive methods in SPECT and CT will be reviewed.

January 28, 2008

Imaging VEGF Receptor Expression
Weibo Cai, Chen Lab

February 4, 2008

Clark Auditorium
Robin P. Choudhury, MA, DM, MRCP
Wellcome Trust Clinical Fellow
Oxford University
Dept of CV Medicine
Hon. Consultant Cardiologist
John Radcliffe Hospital

Microparticles of iron oxide for molecular MRI
Micro-particles of iron oxide (MPIO) have been used for cellular imaging and tracking. For some molecular imaging applications the size of these particles would preclude delivery to the site of interest. However, for imaging endovascular targets, MPIO possess several positive attributes. Firstly, MPIO convey a payload of iron that is orders of magnitude greater than ultrasmall particles of iron oxide (USPIO). Secondly, the effects of MPIO on local magnetic field homogeneity, and therefore detectable contrast, extend a distance many times their physical diameter. Thirdly, once bound to endothelium, MPIO remain intravascular thereby allowing bound MPIO to be readily distinguished from the vessel wall. Finally, conjugated MPIO may offer a generic tool for imaging endothelial-specific markers across a range of vascular pathologies. Accordingly, we have adopted a MPIO-based approach for targeted MRI and applied this to the detection of adhesion molecules on the arterial endothelium (atherosclerosis and brain inflammation) and activated platelets (arterial thrombosis and cerebral malaria).

February 25, 2008

Alway Bldg., M114

Biochemistry by other means: Using imaging to deconstruct T cell recognition
Mark Davis, The Burt and Marion Avery Family Professor, Microbiology and Immunology

March 3, 2008

Photoacoustic Molecular Imaging
Adam de la Zerda, Gambhir Lab

March 17, 2008
Clark Auditorium

Robert Gropler, MD 
Prof. Rad, Med and Bio Eng, Mallinckrodt Institute of Radiology

Diabetic cardiomyopathy: Use of imaging to cross the translational divide

There is a growing epidemic of diabetes mellitus in the United States with a projected increase of 30% in the prevalence of this disease over the next 10 years. Cardiovascular disease is the leading cause of morbidity and mortality in these patients. The myocardial metabolic phenotype of the diabetic heart, an over-dependence on fatty acid metabolism, appears to be an important contributor to the left ventricular dysfunction observed in these patients. Our work has focused on optimizing PET techniques to provide quantitative measurements of myocardial substrate metabolism that are applicable in rodent to human heart. We are then applying these methods to better characterize the metabolic perturbations of the diabetic heart, their contribution to left ventricular dysfunction and the potential role of novel therapeutic approaches to reduce the cardiovascular manifestations of this disease. 

March 31, 2008

A General Method to Regulate Protein Function in Living Mice
Tom Wandless
Assistant Professor (Research) of Chemical and Systems Biology and, by courtesy, of Chemistry, Stanford University

April 7, 2008
Clark Auditorium

Robert Innis, MD, PhD
Chief, Molecular Imaging branch
National Institutes of Health

Evaluation of Novel PET Radioligands for Two Targets: 1) P-gp Efflux Transporter and 2) Inflammation

April 14, 2008

Noninvasive Molecular Imaging of Small Living Subjects using Raman Spectroscopy
Christina Zavaleta, PhD, Gambhir Lab
Interventional Gene Delivery/Therapy for Hepatocellular Carcinoma in a Novel Rat Hepatoma Model
Abhinav Singh, MD, Gambhir Lab

April 21, 2008

Inflammation and Atherosclerosis: Imaging Macrophages in the Vessel Wall
Masahiro Terashima, McConnell Lab

April 28, 2008

Molecular Imaging of Abdominal Aortic Aneurysms
Maureen Tedesco and Geoff Schultz (Ronald Dalman Lab., Vasc. Surgery) Med/Cardiovascular Medicine

May 5, 2008

Nerves on Fire:Imaging Nociception with Manganese-Enhanced MRI (MEMRI)
Deepak Behera, DNB, Biswal Lab
3D Conformal Radiation Therapy System for Small Experimental Animals
Hu Zhou, PhD, Graves lab

May 12, 2008
Clark Auditorium

Stuart Lindsay, PhD
Edward and Nadine Carson Professor of Physics and Chemistry, Biodesign Institute, Arizona State University Single Molecule Tools for Genomics

Single Molecule Tools for Genomics

Genomic diversity, be it at the DNA level, or at the epigenetic level, is probably an essential part of development. There is therefore a need to develop tools capable of sequencing genomes rapidly and sequentially from even single cells, and for mapping post translational modifications that carry the epigenetic code, once again, from single cells, and with high spatial resolution. We are developing atomic-force microscope based methods for mapping post translational modifications on single proteins with nm-scale resolution, and results will be presented for one type of histone modification. We are also pursuing a novel single molecule approach to DNA sequencing which we call "Sequencing by Recognition". It is based on a self-assembled tunnel junction in which an electronic signal is produced when a hydrogen bonded "sandwich" is formed between an electrode, a backbone phosphate, sugar and base to a second base tethered to a second electrode.

May 19, 2008

Modeling cancer associated with loss of function of the retinoblatoma tumor suppressor gene
Julien Sage
Assistant Professor of Pediatrics and of Genetics, Stanford University

May 26, 2008

Mechanisms of telomerase function in stem cells and cancer
Steven Artandi, MD, PhD
Assistant Professor of Medicine, Stanford University

June 2, 2008

Real-time Intravital Imaging of Nanoparticle Behavior in Tumor Neovasculature
Bryan Smith, Gambhir Lab

June 30, 2008

Single-Biomolecule Optical Imaging, Superresolution, and Trapping
W.E. Moerner
Harry S. Mosher Professor and Professor, by courtesy, of Applied Physics, Dept. of Chemistry, Stanford University

July 7, 2008

Development of VEGF121-derived probes for imaging angiogenesis
Gang Niu, PhD, Chen Lab
EGFR imaging with radiolabled antibodies
Hui Wang, PhD, Chen Lab

July 14, 2008
Clark Auditorium

Dean Sherry, PhD
Dir, Advanced Imaging Research Center 
Prof, Rad, UT-Southwestern
Prof, Chem, UT-Dallas 

Towards MR Imaging Agents that Report Biological Function 

MRI contrast agents have become an important tool in clinical medicine. Current Gd3+-based T1 shortening agents require rapid water exchange between an inner-sphere water coordination position and bulk water to produce a substantial change in bulk water relaxation. Current gadolinium agents lack tissue specificity and typically do not respond to their chemical environment. The recent discovery of lanthanide complexes that exchange water only slowly with bulk solvent has opened the door to a new class of agents that provide contrast via a chemical exchange saturation transfer mechanism. While endogenous CEST imaging may prove useful for monitoring certain key metabolites in tissues, exogenous paramagnetic agents (PARACEST) appear to be a versatile new class of MR imaging agents that are highly sensitive to their chemical environment and hence can be designed to "respond" to biological events in vivo. The chemical features that can be used to modulate water exchange in such complexes will be discussed and several applications of PARACEST to molecular imaging will be demonstrated.

July 28, 2008

Progenitor Cell Mediated Neovascularization in Health and Disease
Geoff Gurtner, MD
Associate Professor of Surgery at the Stanford University Medical Center Surgery - Plastic and Reconstructive Surgery

August 4, 2008

Molecular and Functional Profiling of Cardiomyocytes Derived from Human Embryonic Stem Cells

Kitch Wilson, Wu Lab

August 11, 2008
Clark Auditorium

David Townsend, PhD
Prof., Med. & Rad.
Dir., Molecular Imaging and Translational Research Program
UT Med Center

Multimodality imaging of structure and function: from design to applications

From autoradiography to planar X-rays, Computed Tomography (CT) and Magnetic Resonance (MR), morphology and structure has been the mainstay of biological and medical imaging for over a century. While structural changes may suggest the presence of disease, functional changes are more sensitive indicators of early-stage pathology, and with cancer, early detection is the key to a favorable prognosis. Since molecular imaging offers the potential to quantitatively image functional changes in vivo, it is assuming an increasingly important role in the identification, staging and re-staging of human disease. Specifically, Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are sensitive techniques to map human physiology non-invasively through the use of high-resolution imaging devices and appropriate radioactively-labeled biomarkers. However, such metabolic maps do not offer the structural detail associated with anatomical imaging techniques such as CT and MR and therefore dual modality devices such as PET/CT, SPECT/CT or PET/MR that combine both structural and functional information offer a more complete and accurate assessment of the status of disease. Within the past seven years, the development, introduction and rapid adoption of dual modality imaging technology has significantly impacted the medical imaging field. This lecture will discuss the evolution of multimodality instrumentation for the imaging of human disease from the design and development of the technology to applications such as the imaging of cancer and heart disease.

August 18, 2008

From Anatomic Image Guided to Biological Image Guided Radiation Therapy
Lei Xing, PhD
Associate Professor of Radiation Oncology, Stanford University

August 25, 2008

Small molecule probes for non-invasive optical imaging of protease activity
Matthew Bogyo, PhD
Assistant Professor of Pathology and of Microbiology and Immunology and, by courtesy, of Chemical and Systems Biology

September 8, 2008
Clark Auditorium

Mark W. Dewhirst, DVM, PhD 
Gustavo S. Montana Prof, Rad. Onc.
Prof., Path & Bio. Eng.
Duke University

Exploring oxidative stress and HIF-1 in early angiogenesis and response to radiotherapy and chemotherapy 

Using cell lines that contain GFP under control of HIF-1, we found that angiogenesis initiation occurred prior to detection of HIF-1 activity. Tirapazamine prolonged time for detection of HIF-1-GFP, but did not affect angiogenesis initiation. HIF-1-GFP expression paradoxically increased in parallel with increases in vascular pO2 during tumor growth. This may be induced by oxidative stress. We hypothesized that HIF-1-GFP expression would decrease after RT with reoxygenation; however, we found that HIF-1 levels increased after RT; an effect that was mediated by free radicals. Treatment of animals with a SOD mimetic blocked upregulation of HIF-1, sensitized vascular endothelium to damage, and prolonged growth delay after RT. Nitric oxide, produced by infiltrating macrophages was found to be responsible. We completed a phase 1b trial in women with metastatic breast cancer, in which serial biopsies and blood samples were drawn prior to, after a week on paclitaxel, and after two weeks on paclitaxel + the HIF-1 inhibitor, 2ME2. We observed increases HIF-1activity after paclitaxel that were reversed after adding 2ME2. This is the first proof that a HIF-1 response occurs in human patients after drug and that it can be blocked with a HIF-1 inhibitor. These results strongly suggest that free radicals are involved in HIF-1 activation and that blockade of HIF-1 will have therapeutic benefit.

Support: Work supported by grants from the NIH/NCI CA40355, NBIB EB001882, NIH/NCI CA81512, the Duke SPORE for breast cancer, the Hughes Foundation for Medical Research, the Duke Medical Scientist Training Program, the Susan G. Komen Foundation and Entremed Corporation.

September 22, 2008

Hyongsok (Tom) Soh, PhD
Department of Mechanical Engineering
Department of Materials

Rapid in vitro Directed Evolution in Microfluidic Systems

Current techniques in high performance molecular and cellular separations are limited by the inherent coupling among three competing parameters: throughput, purity, and recovery of rare species. 

Microfluidics provides a unique opportunity to decouple these parameters because it allows precise generation of separation forces that are not accessible in conventional, macroscopic systems. 

In this seminar, we will first discuss novel high performance electrokinetic and magnetophoretic separation systems based on microfluidics technology. Next, we present our recent work in applying such systems for Rapid in vitro Directed Evolution (RiDE) and demonstrate extremely fast isolation of affinity reagents (peptides and aptamers) that bind to target molecules with high affinity and specificity.

October 6, 2008

In vivo MRI of embryonic stem cell survival
Jaehoon Chung, M.D., Yang Lab

October 13, 2008
Clark Auditorium

Arthur Toga, PhD 
Dir., Lab of Neuro Imaging 
UCLA Sch of Med

Brain Mapping the Structure and Function of Mice and Men 

In both man and animal models, the ability to statistically and visually compare and contrast brain image data from multiple subjects is essential to understanding normal variability and differentiating normal from diseased populations. This talk describes some of these approaches and their application in basic and clinical neuroscience. Measurement and modeling of anatomy and physiology from gene expression and blood flow to fiber tracking can enable identification of different groups. Identifying biomarkers to study disease progression and the efficacy of therapies requires multiple modalities and probabilistic approaches. There are numerous probabilistic atlases that describe specific subpopulations, measure their variability and characterize the structural differences between them. Utilizing data from structural MRI, we have built atlases with defined coordinate systems creating a framework for mapping data from functional, histological and other studies of the same population in several species. This talk describes the basic approach and some of the constructs that enable the calculation of probabilistic atlases and examples of their results from several different normal and diseased populations. Computational strategies that integrate across modalities and subjects also establish time and data trends across a variety of observations. This talk will also illustrate some approaches useful in understanding multidimensional data and the relationships between them over time. Finally, there will be challenges identified for future mapping and modeling between modalities, time, subjects and species. 

October 20, 2008

Engineered Knottin Peptides: A New Class of Agents for Imaging Integrin Expression in Living Subjects
Jennifer Cochran, PhD
Assistant Professor of Bioengineering, Stanford University

November 17, 2008

18F Sodium Fluoride: An Unfinished Business
Andrei Iagaru, MD, Nucelar Medicine Clinic

November 24, 2008

Molecular Ultrasound: Basics and Applications
Juergen Willmann, MD,
Assistant Professor, Radiology - Diagnostic Radiology, Stanford University
Translational Molecular Imaging Lab

December 1, 2008
Clark Auditorium

Ronald Li, PhD
Associate Professor
School of Medicine
University of California, Davis

Fixing the Heart by Protein Engineering, Gene Therapy and Pluripotent Stem Cells: What are the electrophysiological consequences?

Loss of non-regenerative, terminally differentiated CMs is irreversible; myocardial repair is hampered by a severe shortage of donor cells and organs. Self-renewable human embryonic stem cells (hESCs) and induced pluripotent cells (iPSC) can propagate indefinitely in culture while maintaining their pluripotency, including the ability to differentiate into cardiomyocytes. Therefore, hESCs/iPSCs can potentially serve as an unlimited ex vivo cell source for cell-based heart therapies, and as an experimental model for studying human cardiogenesis and drug screening. In this lecture, our various gene- and cell-based approaches to repair the conduction system and the myocardium, with emphasis on the poorly defined electrophysiological consequences, will be discussed.

December 8, 2008
Clark Auditorium

Robert D. Simari, M.D.
Prof., Medicine
Div. of CV Diseases
Mayo Clinic College of Medicine

Clinical Translation of Cardiovascular Cell Therapies: Defining unmet needs

Early clinical trials of cell therapy for left ventricular dysfunction have demonstrated relative safety and a modest degree of efficacy. These studies have led to enhanced interest in this field and additional clinical trials. Yet, the ideal cell type and their defined mechanisms of action, the ideal patient population and study design remain elusive. This talk will provide an update on the status of cardiovascular cell therapy and will try to define features which will enhance this translation.

Sponsored by: Molecular Imaging Program at Stanford (MIPS) (mips.stanford.edu);
Host: Director, Sanjiv Sam Gambhir, MD, PhD (sgambhir@stanford.edu)

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