MIPS Molecular Imaging Program at Stanford

2007 MIPS Molecular Imaging Seminar Series

Seminar 4:30 − 5:15 pm
Discussion 5:15 − 5:30 pm
Clark Auditorium, Bio-X
Stanford University Campus

You will need the free RealPlayer [ Mac | PC ] to view the webcast of archived lectures.


January 8, 2007
February 2, 2007
February 12, 2007
March 12, 2007
April 9, 2007
May 14, 2007
June 11, 2007
July 9, 2007
August 13, 2007
September 17, 2007
October 8, 2007
November 5, 2007
December 10 2007

Invited Speakers

Michael E. Phelps, Ph.D. - View Webcast
Dean W. Felsher, M.D., Ph.D. - View Webcast
David R. Piwnica-Worms, M.D., Ph.D. - View Webcast
Victor W. Pike, Ph.D. - View Webcast
Brian W. Pogue, Ph.D. - View Webcast
Julie L. Herberg, Ph.D. - View Webcast
Bruce J. Tromberg, Ph.D. - View Webcast
Daniel B. Vigneron, Ph.D. - View Webcast
Jeff W. Lichtman, M.D., Ph.D. - View Webcast
Xiaoliang Sunney Xie, Ph.D. - View Webcast
Martin G. Pomper, M.D., Ph.D. - View Webcast
Mina J. Bissell, Ph.D. - View Webcast
Anna Wu, Ph.D. - View Webcast

Jan. 8, 2007
Clark Auditorium

Michael E. Phelps, Ph.D.
Michael E. Phelps, Ph.D.
Norton Simon Professor
Chair, Dept of Mol & Med Pharm
View Webcast
Molecular Imaging Diagnostics with PET: A new biomarker discovery pathway from cancer biology to patients.

Molecular Imaging Diagnostics with PET: A new biomarker discovery pathway from cancer biology to patients Molecular Imaging diagnostics (MID) with PET consist of an imaging instrument and labeled molecules with properly formulated tracer or pharmacokinetic models representing transport and reactions of the labeled molecule to provide assays of biological, biochemical or pharmacologic processes or to track cells or particles (e.g., nano, viral, etc). These assays provide diagnostic biomarkers of disease, stratification of patients by therapeutic target and assessment of therapeutic efficacy, as well as guiding the drug discovery and development processes. The greatest progress in MID with PET will be in biomarkers and molecular technologies, even through innovation in PET imaging instruments continue.

The goal of this research is to create a novel PET biomarker discover pathway from basic science to patients with a primary focus on cancer. Enabling technologies are being developed along this pathway to accelerate the discovery rate, increase diversity and lower costs to synthesize, validate and use PET biomarkers for MID, as well as to increase availability of MID biomarkers to academic and industry (imaging & pharmaceutical) and clinical diagnostics. A critical step in this process is to get the biology of cancer right develop a knowledge base of the modules (e.g., apoptosis, cell cycle, angiogenesis, etc.) transitioning (re-programming) normal cells to malignant properties and identify critical, controlling mutated proteins in theses transitions as molecular imaging and drug targets.

Studies will be shown to demonstrate the use of biological measures with PET to detect, stage and separate treatment responders from non-responders both after short-term therapy and by whether patients have or do not have the drug target prior to treatment. Integrated microfluidic chips are being developed to synthesize, label and measure the biochemical properties of PET biomarkers. A software package, Kinetics Imaging System (KIS) is employed to convert the kinetics of data collected into information biochemical assays, pharmacokinetics, etc. In vivo and in vitro molecular diagnostics need to become a measurement science.
Jan 22, 2007 Imaging RNA with Spliceosome-Mediated Trans-Splicing
Zac Walls, Gambhir Lab

Nanoparticle-Based Tumor Targeting and Imaging
Weibo Cai, Ph.D., Chen Lab
Jan 29, 2007 Production of radionuclides - The chemistry starts here
David Dick, Ph.D., Head of Cyclotron Physics
Feb 5, 2007
Clark Auditorium

Dean W. Felsher, M.D., Ph.D.
Dean W. Felsher, M.D., Ph.D.
Assoc Prof
Division of Oncology View Webcast
Imaging the Death and Resurrection of Cancer

Feb 12, 2007
Clark Auditorium

David R. Piwnica-Worms, M.D., Ph.D.
David R. Piwnica-Worms, M.D., Ph.D.
Prof., Mol Bio & Pharm
Washington University
View Webcast
Spectral Deconvolution of Multi-Color Reporters for Imaging Signal Transduction Pathways in Real Time

Genetically-encoded imaging reporters introduced into cells and transgenic animals enable noninvasive, longitudinal studies of dynamic biological processes in intact cells and living animals. A wide variety of bioluminescent luciferase proteins are available and when engineered into fusion proteins rather than cloned into promoter/enhancer sequences, these imaging reporters enable fundamental processes such as post-translational modification, signal transduction cascades, protein-protein interactions, oncogenic transformation, and targeted drug action to be temporally and spatially registered in vivo in real time. Furthermore, multi-color post-translational reporters can be simultaneously imaged to deconvolute signals such as normalized IkB kinase activity in longitudinal assays. These reporters provide a rapid, simple, and accurate method for simultaneously measuring multiple bioluminescent reporters in living cells and may provide new contextual insight into cell-specific molecular and regulatory machinery.
Feb 26, 2007 Imaging a Viral-Enhanced Immunotherapy for the Treatment of Cancer
Steve Thorne, Ph.D., Contag Lab

64Cu-Labeled Tetrameric and Octameric RGD Peptides for microPET Imaging of Tumor avb3 Integrin Expression
Zibo Li, Ph.D., Chen Lab
Mar 5, 2007 Clinical Projects in Molecular Imaging
Andrew Quon, Ph.D., Assistant Professor of Radiology
Fellowship Director, Nuclear Medicine Division
Mar 12, 2007
Clark Auditorium

Victor W. Pike, PhD,
Molecular Imaging Branch (MIB)
NIMH, Bethesda, MD
View Webcast
Discovery of Radioligands for Human Brain Imaging with PET In Vivo-Craft or Science?

The physical, chemical and biological basis of positron emission tomography (PET) as a molecular imaging modality in neuropsychiatric research will be briefly described, leading into a discussion of the properties desired in candidate radioligands for PET imaging of brain proteins (e.g. neurotransmitter receptors and transporters). These properties, their assessment and predictability, will be discussed and exemplified with results from established and new PET radioligands.
Mar 19, 2007 Clinical Projects in Molecular Imaging
Michael Mcconnell, M.D.
Director, Cardiovascular MRI Program, Department of Medicine
Associate Director, Cardiovascular Medicine Fellowship Program
Associate Professor, Cardiovascular Medicine, Electrical Engineering (by courtesy), and Molecular and Cellular Physiology (by courtesy)
Mar 26, 2007 In Vivo Imaging of Beta-lactamase Activity
Hequan Yao, Ph.D., Rao Lab

Cytokine-Induced Killer Cell Biology: Chemokine-Directed Trafficking toTumors
Tobi Schmidt, Contag Lab
Apr 2, 2007 Metabolic Imaging using Hyperpolarized MR agents
Daniel Spielman, Ph.D.
Associate Professor of Radiology (Diagnostic Radiology) and, by courtesy, of Electrical Engineering
Apr 9, 2007
Clark Auditorium

Brian W. Pogue, Ph.D.
Brian W. Pogue, Ph.D.
Assoc. Prof.
Thayer School of Engineering
View Webcast
MRI-guided Near-infrared Spectroscopy of Breast Cancer in vivo

Integration of Near-Infrared Spectroscopy (NIRS) into standard medical imaging instrumentation has been slow in developing, yet today there have been major developments which make it achievable on a routine basis. NIRS is combined with Image-guided recovery of the tissue components, using standard MR images, to quantify the spectroscopic features of breast cancer. A prototype system integrating NIRS into a 3T MR breast coil is outlined, and the initial approach to using the MR image as the template upon with spectroscopy is completed are discussed.

The detector scheme for MR or CT-guided NIR is perhaps the most complicated decision for integration, as most useful choices take optical spectroscopy out of the "inexpensive" category. Two prototype systems for frequency domain and broadband spectral imaging of tissue are discussed, and it is shown that the spectral tomography system is ideal for fluorescence or bioluminescence tomography in vivo. This type of hybrid imaging is still in its infancy, yet using it to guide therapy or to properly individualize therapy choice is the next logical step. Use of MRI or CT as the backbone technology to exploit NIRS is a logical step for integration of this modality into clinical use.

At the small animal imaging, much more can be achieved, and the combination of 3T MR with NIRS for small animal studies is also discussed. Molecular tracers such as Epidermal Growth Factor and Protoporphyrin IX are shown to be increased in glioma models. The use of hybrid imaging systems such as image-guided NIRS is likely to be the next major phase of imaging instrumentation development, as it allows quantification of molecular tracers and biophysical imaging of tissue, using contrast mechanisms which are not otherwise available.
Apr 16, 2007 PET: Current and emerging applications in radiation therapy
Billy W. Loo Jr. M.D. Ph.D., D.A.B.R.
Instructor, Department of Radiation Oncology
Thoracic Radiation Oncology Program Leader
Apr 23, 2007 MRI Applications in Molecular Imaging
Mike Mosely, Ph.D.
Associate Professor of Radiology
Apr 30, 2007 Targeted Delivery of TNF to avb3 Positive Tumor Enhanced the Anti-tumor Effect of TNF
Hui Wang, Ph.D., Chen Lab

MicroPET Imaging of Urokinase-type Plasminogen Activator Receptor Expression Using 64Cu-Labeled Peptides
Gang Niu, Ph.D., Chen Lab
May 7, 2007 Image Analysis and Quantitation for Lung Cancer Imaging: From Bedside to Bench
David Paik, Ph.D.
Assistant Professor, Radiology-Diagnostic Radiology
May 14, 2007
Clark Auditorium

Julie L. Herberg, Ph.D.
Physicist, Lawrence Livermore Nat'l Lab
View Webcast
Stretching the limits of MRI through development of microcoil technology and novel contrast agents for molecular imaging.

Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) have been extensively used for chemical, material, biological, and medical applications. Our group at Lawrence Livermore National Laboratory (LLNL) has used Magnetic Resonance Microscopy (MRM) to examine a variety of materials, including polymeric materials and biofilms. During the first part of this Seminar, I will discuss the advantages and limitations of using MRM techniques for analyzing these types of materials. In addition, I will discuss how commercial MRM systems are not well suited for the analysis of very small volumes (on the order of 10 m3 volume element of an MR image) due to the inherent lack of sensitivity of MRI (often greater than g/ml limit of detection). To address the issue of sensitivity of the MRM system, I will discuss our development of rf microcoils, which inherently have large sample filling factors and efficient coupling of the excitation and detection radio frequencies to the sample. LLNL has developed a fabrication methodology suited for development and construction of any desired geometry microcoils with laser lithography. These small NMR coils of various geometries can be prepared to exact specification on curved surfaces with micron level feature sizes. Lithographical techniques can produce rf microcoils, shim coils, and gradient coils. Currently, we are using the rf microcoils to develop a portable microcoil NMR system that consists of a hand-held 450g magnet and an RF probe with laser-fabricated microcoils, which are integrated into a tabletop system. Such a system is ideal for chemical identification of trace substances in the field. Similar principles can be extended to develop highly sensitive MRM for molecular imaging. This technology could eventually lead to a portable MRM system.

The second part of this Seminar will discuss a new type of MRI contrast agent that can provide brighter and more physiologically relevant MR images than the current state-of-the-art in MRI. The MRI contrast agents that we are investigating could target and highlight specific types of tissues and would be highly beneficial for both detection and therapy of cancer. Attachment of a Gd3+ contrast agent, Gd-DOTA, and an antibody targeting mechanism to a water-soluble silica coated quantum dot may allow for tissue specific contrast. Results will be presented to demonstrate that Gd-DOTA attached to quantum dot displays a greater contrast to traditional, non-specific contrast agents. In addition, I will discuss the advantages of our approach, including greater relaxivity and greater simplicity of the synthesis process.

Both the development of lithographically produced microcoils and nanoparticles coated with a water-soluble thin silica shell doped with paramagnetic Gd3+ ions attach allow for flexibility in MRM and MRI that will provide a basis for new developments in this field. This work was performed under the auspices of the U.S. Department of Energy by the University of California Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48
May 21, 2007 Stanford Radiology 3D Lab: Clinical and Research Highlights
Sandy Napel, Ph.D.
Associate Professor of Radiology
Co-Director, 3D Medical Imaging Laboratory
Associate Member, MIPS
June 4, 2007
4:30-5pm Reception
5-5:45pm Seminar
5:45-6pm Q&A
In Vivo evolution of ribozyme
Hui Wang, Ph.D., Chen Lab

Fluorescent labeling of RNA using small-molecular probes
Anca Dragulescu-Andrasi, Ph.D., Rao Lab
Jun 11, 2007
Clark Auditorium

Bruce J. Tromberg, Ph.D.
Laser Microbeam and Medical Program,
Beckman Laser Institute and Medical Clinic,
View Webcast
Medical Imaging in Thick Tissues Using Diffuse Optics

Medical diagnostic techniques based on near infrared (NIR) transillumination were first introduced more than 70 years ago to detect breast cancer. Although NIR light penetrates tissue to depths of several centimeters, early methods were not successful due to the fact that these approaches were qualitative and did not account for distortions from multiple light scattering.

Recent advances in temporal- and spatial- frequency-domain "photon migration" now make it possible to separate light absorption from scattering in thick tissues. Temporal frequency-domain methods measure the phase shift and amplitude of MHz - GHz intensity-modulated waves (1), while spatial frequency-domain techniques utilize structured light patterns to form wide-field images of tissue optical properties (2). Both approaches are based on comparing measured data with radiative transport models to form images, i.e. "diffuse optical imaging (DOI)", and acquire spectra, i.e. "diffuse optical spectroscopy (DOS)".

This talk reviews principles of light propagation in tissue and describes the development of DOI/DOS for non-invasively characterizing tissue structure and biochemical composition. Particular emphasis is placed on the development of broadband methods for quantitative, high-resolution measurements of NIR absorption and scattering spectra between 600-1000 nm (3). These data are used to determine the tissue concentration of deoxygenated hemoglobin, oxygenated hemoglobin, methemoglobin, lipid, and water, as well as the tissue "scatter power". Clinical study results are shown highlighting the sensitivity of broadband DOS to metabolic changes in breast cancer detection and therapeutic drug monitoring (4,5). Broadband spatial frequency-domain imaging is used in pre-clinical animal models to dynamically map intrinsic brain signals and monitor the efficacy of chemotherapeutic agents. These findings will be placed in the context of conventional imaging methods, such as MRI, in order to assess the current and future role of diffuse optics in medical imaging (6).
June 18, 2007
Clark S360
Image Guidance During Interventional Procedures: Beyond Fluoroscopy
Rebecca Fahrig, Ph.D.
Assistant Professor, Department of Radiology
June 25, 2007 Protein modifications that regulate oxygen sensing and tumor angiogenesis
Amato Giaccia, Ph.D.
Professor & Director, Division of Radiation and Cancer Biology
Department of Radiation Oncology
Stanford University School of Medicine
July 9, 2007
Clark Auditorium

Daniel B. Vigneron, Ph.D.
Daniel B. Vigneron, Ph.D.
Prof., Radiology, UCSF
View Webcast
Application of Hyperpolarized Carbon-13 MR Metabolic Imaging for Prostate Cancer Research

Carbon-13 MRS of labeled substrates has the potential to improve the characterization of prostate cancer based on known changes in metabolic fluxes through glycolysis, the citric acid cycle and fatty acid synthesis. To study this 13C metabolism in vivo, we have applied an exciting new advance in metabolic imaging, hyperpolarized 13C MR described by Ardenkjaer-Larsen JH, et al. Using this method, 50,000+ fold signal enhancement allows in vivo detection of a 13C hyperpolarized compound such as pyruvate and its metabolic products following injection. We applied this method to study transgenic mouse models of prostate cancer. Using a 15 second 3D MRSI sequence, we have observed rapid uptake of pre-polarized 13C-pyruvate in vivo and its metabolism to 13C labeled lactate in primary and metastatic tumors. Significantly higher 13C-lactate levels were detected in tumors as compared to normal tissues.
July 16, 2007 Recent advances in computed tomography
Norbert Pelc, Ph.D.
July 23, 2007 Functional Neuroimaging - a Biomarker?
Gary Glover, Ph.D.
July 30, 2007 Ribozyme Mediated Imaging of mRNA-update
Gayatri Gowrishankar, Ph.D., Rao Lab

Studying Drug Modulated Multi-protein Interactions by Split Reporters
Paul Ramasamy, Ph.D., Gambhir Lab
Aug 6, 2007 A site-specific integration system for non-viral gene therapy
Michele Calos, Ph.D.
Aug 13, 2007
Clark Auditorium

Jeff W. Lichtman
Prof., Mole & Cell Bio
View Webcast

Aug 20, 2007 Imaging prodrug conversion in an effective cancer therapy using a new drug and evolved enzymes
A.C. Matin, Ph.D.
Aug 27, 2007 18F-labeled Proteins as Probes for Positron Emission Tomography (PET)
Mohammad Namavari, Ph.D.
Sept 10, 2007 Imaging brain hemodynamics and oxygenation in patients with cerebrovascular disease
Greg Zaharchuk, Ph.D.
Sept 17, 2007
Clark Auditorium

Xiaoliang Sunney Xie, Ph.D.
Prof. of Chemistry
Harvard University
View Webcast
Single-molecule Imaging of Transcription, Translation and Replication in Living Cells; and Vibrational Imaging of metabolites and Drugs in Living Organisms

The combination of specific probes and advanced microscopy allows detecting and tracking a particular protein with single-molecule sensitivity, nanometer spatial precision, and millisecond time resolution in living bacterial cells. This yields quantitative information regarding many fundamental processes in molecular biology. Metabolites and drugs, usually difficult to detect, can be imaged and monitored in living organisms with coherent anti-Stokes Raman scattering (CARS) microscopy that requires no fluorescence labels, and offers extremely high sensitivity.
Sept 24, 2007 Accelerating tomographic image reconstruction for positron emission tomography using computer graphics hardware
Guillem Pratx, Levin Lab

Site specific conjugation of proteins to quantum dots
Zuyong Xia, Ph.D., Rao Lab
Oct 1, 2007 Nanoplatforms for molecular imaging and therapy
Xiaoyuan (Shawn) Chen, Ph.D.
Oct 8, 2007
Clark Auditorium

Martin G. Pomper
M.D., Ph.D.
Assoc. Prof. of Radiology
Johns Hopkins University
View Webcast
Translational Molecular Imaging for Oncology

Although most clinical diagnostic imaging studies employ anatomic techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, much of radiology research currently focuses on adapting these conventional methods to physiologic imaging as well as on introducing new techniques and probes for studying processes at the cellular and molecular levels in vivo, i.e. molecular imaging. Molecular imaging promises to provide new methods for the detection of minimal changes in diseased tissue and support for personalized therapy. Although molecular imaging has been practiced in various incarnations for over 20 years in the context of nuclear medicine, other imaging modalities have only recently been applied to the noninvasive assessment of physiology and molecular events. Nevertheless, there has been sufficient experience with specifically targeted contrast agents and high-resolution techniques for MR imaging and other modalities that we must begin moving these new technologies from the laboratory to the clinic. Several projects relevant to oncology will be discussed with emphasis on how they were/will be moved from the bench to the clinic.
Oct 15, 2007 Monitoring Stem Cell Fate by Bioluminescence Imaging
Helen Blau, Ph.D.
The Donald E. and Delia B. Baxter Professor of Pharmacology and Professor of Chemical and Systems Biology
Oct 22, 2007 Screening for Cancer: Does Early Detection Save Lives?
Sylvia Plevritis, Ph.D.
Oct 29, 2007 Glycobiology at the cell surface
Jennifer Prescher, Ph.D., SMIS Fellow

Qdot Conjugates for in vivo Molecular Imaging
Min-Kyung So, Ph.D., Rao Lab
Nov 5, 2007
Clark Auditorium

Mina J. Bissell
Lawrence Berkeley Laboratory
Berkeley, CA
View Webcast
The architectural basis of tissue specificity: the relationship between the genome and 3D structure

Nov 12, 2007 CANCELLED
Nanoplatforms for Molecular Imaging and Therapy

Xiaoyuan (Shawn) Chen, Ph.D.
Nov 19, 2007 Advanced Imaging of Articular Cartilage: From Morphology to Physiology
Garry Gold, Ph.D.
Nov 26, 2007 Application of magnetic nanoparticles for multimodality imaging
Ha-Young Lee, Ph.D., Chen Lab

18F Labeling of Biomolecules Using Anionic Fluoride in an Aqueous Environment
Christopher Caires, Guccione Lab
Dec 3, 2007 New technologies to enhance the molecular sensitivity of positron emission tomography
Craig Levin, Ph.D.
Dec 10, 2007
Clark Auditorium

Anna Wu, Ph.D.
Dept. of Molec & Med Pharm
Assoc. Dir., CIMI
View Webcast
Antibodies and Antimatter: ImmunoPET for Imaging Cancer

January 3, 2008 Predicting tumor response to targeted therapy from non-invasive imaging
Jill Lin, Paik Lab

In vivo imaging of embryonic stem cell transplantation immunobiology
Rutger-Jan Swijnenburg, Ph.D., Wu Lab

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

If you would like to be included on the MIPS email distribution list for weekly meeting reminders, contact Susan Singh.

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