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Functional and molecular MR imaging of angiogenesis: seeing the target, seeing it work
1Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel. michal.neeman@weizmann.ac.il
Abstract:
Intensive research over the last years led to the discovery of multiple molecular pathways and intricate regulatory network controlling the growth and regression of blood vessels in general and angiogenesis in particular. The difficulties in elucidation of the regulation of angiogenesis, stems from the inherent complexity due to participation of many cell types, under a dominant impact of physiological and environmental effects of flow, perfusion, and oxygenation. Major advances were achieved with the use of sophisticated transgenic mice models engineered so as to provide spatially and temporally controlled expression of specific factors alone or in combination. In vivo analysis of these models frequently requires the use of non-invasive imaging modalities for measurement of functional parameters of the vasculature along with dynamic molecular information. Optical methods are extensively applied for the study of angiogenesis [Brown et al., 2001] but provide very limited tissue penetration. MRI offers the advantage of being non-invasive with uniform and relatively high spatial resolution for deep tissues. Multiple MRI approaches for monitoring angiogenesis were developed over the last years, each looking at a particular step in the process. The aim of this paper is to analyze the clinical, pharmaceutical, and biological needs for imaging of angiogenesis, and to critically evaluate the strengths and weaknesses of functional and molecular imaging for monitoring angiogenesis. The inherent problem of validation of different measures of angiogenesis, and the advantages and limitations associated with application of MRI based methods, as surrogates for other measurements of angiogenesis will be discussed. The terms molecular imaging and functional imaging are frequently loosely defined with a significant overlap between the two. For the sake of this paper we will apply a narrower definition of both terms, where molecular imaging will apply to methods directed towards detection of specific biological molecules that participate directly in (regulation of) a physiological process; while functional imaging will be used to describe those methods that aim to detect the physiological response to a defined (molecular) stimulus.
Insights
Magnetic Resonance Imaging (MRI) offers a non-invasive method to monitor angiogenesis, a complex process involving blood vessel growth. This review critically evaluates MRI
Area of Science:
- Vascular Biology and Imaging
- Biomedical Engineering
- Translational Medicine
Background:
- Angiogenesis, the growth of new blood vessels, is a complex process regulated by numerous molecular pathways and influenced by physiological factors.
- Elucidating angiogenesis regulation is challenging due to the involvement of multiple cell types and environmental influences like oxygenation and blood flow.
- Advanced transgenic mouse models and non-invasive imaging are crucial for in vivo analysis of angiogenesis.
Purpose of the Study:
- To analyze clinical, pharmaceutical, and biological needs for imaging angiogenesis.
- To critically evaluate the strengths and weaknesses of functional and molecular imaging techniques for monitoring angiogenesis.
- To discuss the validation of angiogenesis measures and the role of MRI-based methods.
Main Methods:
- Review and critical evaluation of existing literature on angiogenesis imaging.
- Analysis of Magnetic Resonance Imaging (MRI) approaches for monitoring angiogenesis.
- Comparison of functional and molecular imaging techniques, with defined scopes.
Main Results:
- Optical imaging methods have limited tissue penetration, whereas MRI offers non-invasive deep tissue imaging with high resolution.
- Multiple MRI approaches exist for monitoring specific steps of angiogenesis.
- Clear definitions are proposed: molecular imaging targets specific molecules, while functional imaging detects physiological responses.
Conclusions:
- MRI presents significant advantages for non-invasive, high-resolution monitoring of angiogenesis in deep tissues.
- Functional and molecular imaging, particularly MRI-based methods, require careful validation as surrogates for other angiogenesis measurements.
- A precise distinction between functional and molecular imaging is essential for clarity in angiogenesis research.