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Published on: July 23, 2012
Molecular MRI approaches to the detection of CNS inflammation
Nicola R Sibson1, Daniel C Anthony, Sander van Kasteren
1CR-UK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK. nicola.sibson@rob.ox.ac.uk
Abstract:
Inflammation is a key component of many neurological diseases, yet our understanding of the contribution of these processes to tissue damage remains poor. For many such diseases, magnetic resonance imaging (MRI) has become the method of choice for clinical diagnosis. However, many of the MRI parameters that enable disease detection, such as passive contrast enhancement across a compromised blood-brain barrier, are weighted towards late-stage disease. Moreover, whilst these methods may report on disease severity, they are not able to provide information on either disease activity or the underlying molecular processes. There is a need, therefore, to develop methods that enable earlier disease detection, potentially long before clinical symptoms become apparent, together with identification of specific molecular processes that may guide specific therapy. This chapter describes the methodology for the synthesis and validation of two novel, functional MRI-detectable probes, based on microparticles of iron oxide (MPIO), which target endothelial adhesion molecules. These contrast agents enable the detection of acute brain inflammation in vivo, at a time when pathology is undetectable by conventional MRI. Such molecular MRI methods are opening new vistas for the acute diagnosis of CNS disease, together with the possibility for individually tailored therapy and earlier, more sensitive assessment of the efficacy of novel therapies.
Insights
Novel magnetic resonance imaging (MRI) probes detect acute brain inflammation in vivo, enabling earlier diagnosis of neurological diseases. These functional MRI agents target endothelial adhesion molecules for improved disease detection and therapy assessment.
Area of Science:
- Neuroscience
- Medical Imaging
- Biochemistry
Background:
- Inflammation is crucial in neurological diseases, but its contribution to tissue damage is poorly understood.
- Current magnetic resonance imaging (MRI) methods detect late-stage disease and lack information on disease activity or molecular processes.
- There is a need for early detection methods and identification of molecular targets for tailored therapies.
Purpose of the Study:
- To develop novel, functional MRI-detectable probes for early detection of acute brain inflammation.
- To validate microparticles of iron oxide (MPIO)-based probes targeting endothelial adhesion molecules.
- To enable in vivo detection of inflammation before it is visible with conventional MRI.
Main Methods:
- Synthesis and validation of two novel microparticles of iron oxide (MPIO)-based contrast agents.
- Probes designed to target endothelial adhesion molecules for detection of inflammation.
- In vivo testing using functional MRI to assess inflammatory changes in the brain.
Main Results:
- Developed novel MPIO-based probes for functional MRI.
- Demonstrated in vivo detection of acute brain inflammation.
- Detected pathology undetectable by conventional MRI, indicating early disease stages.
Conclusions:
- Functional MRI with novel MPIO probes enables early diagnosis of acute CNS inflammation.
- These molecular MRI methods offer potential for tailored therapies.
- Facilitates earlier and more sensitive assessment of novel therapeutic efficacy.
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