California NanoSystems Institute
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May 28, 2013

Mark S. Cohen, Ph.D.
Professor of Psychiatry, Neurology, Radiology, Biomedical Physics, Psychology, and Bioengineering, UCLA
A unified theory of images?: what we see is what we know
Abstract: Images are used in science for communication and for discovery in virtually all disciplines. Now, in part due to the extraordinary advent of a near fully digital life style, we are in the turbulent core of a revolution in imaging. Here at UCLA, we have proposed that it is timely that there should be a new science of imaging, per se, that seeks common understanding of how we approach data images, in particular. My purpose here is mostly to lay out some of the problems that seem worthy of study: veridicality, data compression and expansion, the role of aesthetics, the extraction of quantitative information, etc. to help seed future work in these important areas. Fundamental to this work is the acceptance that the exploration must be interdisciplinary: dramatic advances in imaging have been made over ten orders of magnitude from observation of electrons to galaxies. Finally, I will present the thesis that our understanding of images is tied closely to the physiology of perception, and that a satisfying understanding of images requires knowledge of the brain mechanisms that limit visual perception and cognition.

Speaker Bio: Mark Cohen is a Professor of Psychiatry, Neurology, Radiology, Biomedical Physics, Psychology, and Bioengineering at UCLA. His research has focused on the development of novel imaging technologies - instrumentation and algorithms - to address crucial questions in neuroscience. He has made crucial contributions in ultra-fast magnetic resonance imaging (MRI), functional MRI, electroencephalography and multimodal functional imaging and in the cognitive sciences.

April 23, 2013

Bruce Tromberg, Ph.D.
Laser Microbeam and Medical Program, Beckman Laser Institute and Medical Clinic, University of California, Irvine
Medical Imaging in Thick Tissues Using Diffuse Optics
Abstract: Quantitative imaging in thick tissues is a significant challenge due to distortions from multiple light scattering. Several methods have been developed to quantify multiple light scattering and measure tissue function and composition. This talk describes the development of Diffuse Optical Spectroscopy and Imaging (DOSI) using spatially- and temporally-modulated sources and model-based analyses. DOSI is capable of dynamic in vivo functional imaging with variable, but limited, spatial localization. Quantitation of multiple optical contrast elements including absorption, scattering, fluorescence, and speckle can be achieved using methods for controlling optical path length in conjunction with computational models. This allows formation of 2 and 3D images of various optical and physiological properties such as blood flow, vascular density, extracellular matrix composition, and cellular metabolism. Particular emphasis is placed on determining the tissue concentration of oxy- and deoxyhemoglobin, lipid, and water, as well as tissue scattering parameters. Clinical study results will be shown highlighting the sensitivity of broadband DOSI to breast tumor metabolism with sufficient sensitivity for cancer detection and therapeutic drug monitoring. Broadband spatial frequency-domain imaging is used in pre-clinical animal models to dynamically map intrinsic brain signals, monitor the efficacy of chemotherapeutic agents, and form depth-resolved tomographic images of fluorescence and hemodynamics. These findings will be placed in the context of conventional imaging methods in order to assess the current and future role of diffuse optics in medical imaging.

Speaker Bio: Dr. Tromberg is the Director of the Beckman Laser Institute and Medical Clinic (BLI) at the University of California, Irvine (UCI) and principal investigator of the Laser Microbeam and Medical Program (LAMMP), an NIH National Biomedical Technology Center. He is a Professor in the departments of Biomedical Engineering and Surgery, co-leads the Onco-imaging and Biotechnology Program in UCIís Chao Family Comprehensive Cancer Center, and has been a member of the BLI faculty since 1990. His research interests are in Biophotonics and Biomedical Optics, including diffuse optics, non-linear microscopy, cancer imaging, and photodynamic therapy.
April 09, 2013

Andre Nel, M.D., Ph.D.
Professor of Medicine, Chief of the Division of NanoMedicine, Director of UC CEIN, David Geffen School of Medicine at UCLA
Nanomedicine and Cancer
Abstract: Over the past decade, nanomedicine and nanobiology have undergone a dramatic transformation from ideological fantasies to real science. Nanomaterials provide major analytical, therapeutic and diagnostic advantages over conventional molecule-based structures and approaches. Moreover, much of biology is executed at the nanoscale level, therefore providing a rational approach to using discovery about the structure and function of engineered nanomaterials at the nano/bio interface to interrogate disease, provide diagnostic tools, treatment, and imaging at a level of sophistication not possible before. After a brief introduction of nanomedicine I will use our multifunctional mesoporous silica nanoparticle (MSNP)-based carrier system to demonstrate how rapid throughput discovery at the nano/bio interface and iterative design can be used to provide improved nanocarriers for treatment of cancer. One example is overcoming multidrug resistance by designing MSNP surfaces that allows for the co-delivery of anticancer drug and siRNA into drug-resistant cancer cells. The functionalization of the particle surface allows electrostatic binding of the chemotherapeutic agent, doxorubicin (Dox), to the porous interior. Phosphonate modification allows exterior coating with the cationic polymer, polyethyleneimine (PEI), which endows the carrier with the ability to bind and deliver P-glycoprotein (Pgp) siRNA that silences the expression of the efflux protein. Following the establishment of a Dox-resistant MCF-7 breast cancer xenograft model in nude mice, we demonstrated that a 50 nm MSNP functionalized by a polyethyleneimine-polyethylene glycol (PEI-PEG) copolymer provides protected delivery of Dox and Pgp siRNA to the tumor site. This design was chosen for its effective biodistribution properties, reduced reticuloendothelial uptake, and the ability to have 8% of the injected dose retained at the tumor site. Compared to free Dox or the carrier loaded with drug alone, the dual delivery system resulted in synergistic inhibition of tumor growth. Analysis of multiple xenograft biopsies demonstrated significant Pgp knockdown at heterogeneous tumor sites, which also correspond to the regions in which, as result of disappearance of drug exporter expression, Dox had access to the nucleus and could induce cytotoxicity. Dox encapsulation by the carrier was associated with reduced systemic side effects, including cardiotoxicity. This work was recently published in ACS nano (2013). Since one of the major factors in the heterogeneous distribution of the carrier pertains to interference in vascular access is a result of the tumor stroma blocking vascular fenestrations, we are currently working on the development of a pair of nanocarriers, one of which is capable of reducing pericyte coverage of fenestrations and the second providing drug and siRNA delivery. We are testing this approach in an animal model for pancreatic cancer.