Optical and fMRI Signal Sources in Brain Imagery.

Lead Research Organisation: University of Sheffield
Department Name: Psychology

Abstract

Recent years have seen a rapid and significant exploitation of techniques for imaging brain activity in a wide range of clinical and experimental settings. Two of these techniques called PET (Positron Emission Photometry) and fMRI (functional Magnetic Resonance Imaging) in particular, exploit the coupling between changes in neural activity and their associated metabolic demands. These demands are satisfied by increased cerebral blood flow in much the same way as increased muscular activity involves increased blood flow to the muscles. The changes in the proportions of oxygenated and deoxygenated blood which provide the magnetic contrast that underpins the fMRI signal is called BOLD (Blood Oxygen Level Dependent) contrast. However, although the above techniques can be used to understand which areas of brain are involved in different tasks and how this is affected by injury, the underlying physical basis of how neurons regulate their blood supply is not well understood. The imaging techniques exploit the fact that increased activity produces localised increases in blood flow but basic research into the relationships between neural activity, the associated metabolic demands and changes in regional cerebral blood flow is still needed. Components of the proposed co-operative group will develop techniques to improve fMRI and optical imaging to understand how different parts of the brain communicate to organise complex behaviour. Another component (already funded by the EPSRC) is currently developing novel ways of analysing neuroimaging data. Other components are using the techniques developed by other projects to investigate the effects of cocaine on brain activation and visual cortical function following repair in animal models of human retinal disease (retinitis pigmentosa and age-related macular degeneration). Another component project is investigating how cue salience affects the magnitude and latency of the hemodynamic response. The results of these studies and the proposed experiments will be used to inform the design and analysis of fMRI imaging in humans.

Technical Summary

Recent years have seen an increasing exploitation of functional magnetic resonance imaging (fMRI) of brain activity in a wide range of clinical and experimental settings. However, the underlying physical basis of how neurons regulate their blood supply is not well understood. Basic research into the relationships between neural activity, the associated metabolic demands and changes in regional cerebral blood flow requires a degree of experimental control best achieved through the use of animal models. The current co-operative project therefore proposes to use a 3 Tesla animal MRI system recently upgraded with a new MRRS spectrometer console, in combination with optical imaging, laser Doppler flowmetry and multi channel electrophysiology to investigate the nature of coupling of neural activity to the hemodynamic response and BOLD fMRI signal.
We aim to investigate questions concerning a) basic neural activity ? hemodynamic response; and b) systems issues which will utilize the developing imaging technology and related analysis methods:
Neural Activity and the Hemodynamic Response
1. The research will develop a formal model linking changes in electrophysiological activity in the different cortical laminae with changes in blood flow and volume. This will be integrated with a model of capillary oxygen transport blood flow and changes in hemoglobin oxygenation to refine a biophysical model of the functional BOLD MRI signal.
2. The forward model of the hemodynamic response to neural activation will be used to explore different analysis strategies for functional magnetic imaging data from event related studies investigating the modulatory influences of different brain regions on one another.
3. Advanced MRI techniques for mapping water mobility (self-diffusion) and its anisotropy will be optimised and applied in order to probe brain microstructure and its alterations upon brain activity (neuronal swelling).
Systems Issues
4. Optical imaging spectroscopy (OIS), laser Doppler flowmetry (LDF), MRI and electrophysiology will be used to study cocaine-induced changes in neural and hemodynamic responses to whisker stimulation, to elucidate cocaine?s enhancement of the whisker sensory response.
5. The modulation by cue salience of the hemodynamic response to stimulation will be determined using the partially restrained unanaesthetised rat preparation. Stimulation of whisker, fore and hind paw will be associated with reinforcement.
6. Visual cortical adaptation, which occurs following degeneration of the retina, will be investigated using both optical imaging and fMRI. How various reparative strategies to slow or repair the degenerating retina affect the process of adaptation will be the major issue addressed in this component.
 
Description BBSRC Project Grant
Amount £315,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2007 
End 06/2011
 
Description CRUK Imaging Technologies in Cancer
Amount £2,000,000 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2009 
End 08/2014
 
Description EPSRC Grand Challenges in Nanotechnology EP/G062137/1 Engineering Virus-like Nanoparticles for Targeting the Central Nervous System - shared with J Berwick
Amount £1,062,955 (GBP)
Funding ID EP/G062137/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 04/2009 
End 04/2012
 
Title Investment in Amimal fMRI infrastructure 
Description This grant helped investment in our 3 and 7T imaging facilities 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact We are now an intergrated facility within the University and have the potential to exploit further imaging opportunities. 
 
Description Univeristy wide collaboration on a EPSRC Nanoparticle Grant 
Organisation University of Bath
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Our role in this collaboratio is to perform all the Optical and fMRI imaging to monitor drug delvery to the CNS and assess Motor Neuron disease progression
Collaborator Contribution New methods are being developed that can be used for our research questionsChemistry make the nanoparticle and label them with flourescnece and we can use this to measure blood flow
Impact Developnment of in vivo optical flourescence imaging and biomarkers of disease progression
Start Year 2008
 
Description Univeristy wide collaboration on a EPSRC Nanoparticle Grant 
Organisation University of Sheffield
Department Department of Biomedical Science
Country United Kingdom 
Sector Academic/University 
PI Contribution Our role in this collaboratio is to perform all the Optical and fMRI imaging to monitor drug delvery to the CNS and assess Motor Neuron disease progression
Collaborator Contribution New methods are being developed that can be used for our research questionsChemistry make the nanoparticle and label them with flourescnece and we can use this to measure blood flow
Impact Developnment of in vivo optical flourescence imaging and biomarkers of disease progression
Start Year 2008