Imaging of mice and men; adventures in multispectral imaging

Abstract

Cancer of the brain and CNS account for only 2% of new cancer cases in the UK however it is responsible for 7% of cancer deaths of those aged under 70 years of age. Although surgery falls short of a cure it is the primary method of treatment. Two of the key problems in tumour surgery in the brain are a) that many tumours are visually indistinguishable from normal tissue even for experienced surgeons and b) that the risk of post-surgical neurological deficit is related to the proximity of functional (or 'eloquent') neurological tissue. In collaboration with surgeons at the Southampton University NHS Hospitals Trust we seek to address both of these problems. Firstly there is literature evidence that normal and neoplastic tissue have different spectral characteristics in the visible and near-infrared region. We investigate whether these can be practically imaged intraoperatively to establish disease state. Secondly the redox state of haemoglobin is known to affect it's visible and near-infrared spectral characteristics. This project investigates whether it is possible to identify the haemodynamic response associated with functional activity intraoperatively in the human brain. Prion diseases are fatal chronic neurodegenerative diseases of animals and man. They have gained notoriety due to recent outbreaks of Bovine Spongiform Encephalopathy (BSE) and the evidence that they can be transmitted between species, including to man. Exposure to BSE infected material has been shown to cause variant Creutzfeldt-Jacob disease in man. Prion disease is also used as a model of other neurodegenerative diseases, such as Alzheimers disease. Remarkably little is known about this class of disease including the specific cause of the neurodegeneration. Prions are a mis-folded protein which have a different conformation than the normal protein. Certain spectral features in the mid infrared region are associated with protein conformation. In collaboration with neuro-biologists within the university and using a synchrotron light source we investigate the application of multispectral imaging in early stage prion disease. By analysis of the protein conformation sensitivity of the mid infrared spectra (with particular interest in the Amide I band) we seek to identify structurally relevant markers in a mouse model before clinical symptoms of the disease are evident. This may lead to better understanding of the disease progression and the neurotoxic element.

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