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Wissenschaftliche Aktivitäten

Auszug der wissenschaftlkichen Projekte, welche in Kooperation mit dem Weizmann Institute of Science durchgeführt wurden

 

A modular nanosystem platform for advanced cancer management (W.I. partner: Prof. Irit Sagi) FP7 project

An estimated 3.2 million new cancer cases and 1.7 million deaths per year in Europe define cancer as a crucial public health problem especially as these numbers are anticipated to increase. Thus, the SaveMe project will address major urgent needs for cancer diagnosis and treatment, by exploiting partners’ expertise, vast experience and most recent research achievements. SaveMe proposes the design and development of novel modular nanosystems platform integrating advanced functionalized nano-core particles and active agents (Fig. 1.1). The modular platform will enable the design of diverse active nanosystems for diagnostic or therapeutic applications.

STEM image of a worm-shaped nanoparticle (W.I. partner: Prof. Michael Elbaum, joint project with Prof. Arie Orenstein, Sheba Medical Center)

Nanotechnology holds great promise in cancer medicine to revolutionize therapy and diagnosis. With high surface area, nanoscopic objects afford the opportunity to present lots of biomarkers. This feature of nanomaterials makes development of theranostics and multimodal diagnostics possible.

Super magnetic iron oxide naoparticles (SPION) with their inherent magnetic properties are one of the most appealing materials for buildup of therapeutic and diagnostic agents. These biodegradable particles till far are the only NPs that have been introduced into routine clinical imaging as T2-shortening contrast agents which can reproduce the underlying MRI signal. Most researches till far have been done with emphasis on SPION with spherical morphology which mostly synthesized through co-precipitation of iron salts through in-situ coating with biocamptaible sugar, polymer or protein. However at a specific ratio between iron salts and coating materials, the spherical iron oxide core will be joined together along one dimension to produce structures about 50-80 nanometers long named “Nanoworm” inspired by the similarity to earthworm but in about 3 million times smaller size. Each nanaworm consists of average 7 cores, so they can produce stronger MRI signals than their component spherical ones.

Dynamic contrast-enhanced fluorescent imaging (W.I. partner: Dr. Vachyslav Kalchenko and Prof. Alon Harmelin)

In vivo optical imaging commonly used in clinical and especially in preclinical research. This optical method can exploit an enormous range of endogenous and exogenous forms of contrast that provide information about the anatomical structures and functions of tissues ranging from single cell to entire organisms. Static fluorescent imaging provides an extraordinary contrast and specificity but it has serious limitations that relate to the interaction between light and tissue.

Herein discussion will be delivered about benefits and limitations of Dynamic Fluorescent Imaging (DFI) or alternatively so called Dynamic Contrast-Enhanced small animal fluorescent imaging (DyCE). DFI enables to observe not only static distributions of fluorescent contrast agent, but to examine and characterize dynamic events related to normal physiology or disease progression in real time.

DFI can also provide quantitative, in vivo information of organ function without additional expensive equipment, as it employs standard and simple acquisition setup. We present several examples of improved preclinical method for dynamic fluorescent imaging of cerebral hemodynamics facilitated by unsupervised image enhancement based on constraint Factor Analysis. The proposed method is based on a previously introduced Transcranial Optical Vascular Imaging (TOVI). TOVI employs natural and sufficient transparency through the intact cranial bones of a mouse. Fluorescent image acquisition is performed at a video rate after intravenous fluorescent tracer administration.

Factor Analysis of Medical Image Sequences (FAMIS) is used to extract structures with different temporal characteristics from dynamic contrast enhanced studies without making any a-priori assumptions about physiology. Factor Analysis applied on an image sequence obtained after fluorescent tracer administration is allowing extracting valuable information about cerebral blood vessels anatomy and functionality without a-priory assumptions of their anatomy or physiology while keeping the mouse cranium intact. Unsupervised color-coding based on Factor Analysis enhances visibility and distinguishing of blood vessels belonging to different compartments. Optimal DFI requires only minimal efforts in temporal and spatial processing of acquired fluorescent images. The advantage DFI based on FA especially in case of transcranial imaging is the unsupervised separation of different dynamic structures. DFI still has limitations linked to issues of light tissue interactions.

Example of color-coded and automatically enhanced (RGB) image of the intact mouse cranium based on superposition of 3 factors. F1- red corresponds predominantly with arterial phase. F2 - green corresponds predominantly with venous phase. F3- blue corresponds predominantly with late venous phase.