Improving The Assessment Of Brain Tumour Treatment Outcome Using 18F-FDOPA PET-MRI Fusion
Funder
National Health and Medical Research Council
Funding Amount
$660,666.00
Summary
The mortality rate within the first year of diagnosis for high-grade brain tumours is approximately 80%. A major factor contributing to poor outcome measures is the limitation of current neuroimaging techniques. In a novel approach we propose to combine the information available from MRI and PET images to better define the extent of the tumour and provide markers of early treatment response. This improved diagnostic information should improve survival rates.
Episodic Memory Dysfunction As A Basis For Auditory Hallucinations In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$278,517.00
Summary
Auditory hallucinations (AHs) occur frequently in people who suffer from schizophrenia. This symptom usually involves hearing voices that the hallucinator firmly believes originate from other people. The voices are often intrusive, abusive and persecutory. They are a source of significant stress and may result in self harm or harm to others. Our investigations will attempt to provide experimental support for the theory that AHs represent a misremembering of voices which were heard in the past. W ....Auditory hallucinations (AHs) occur frequently in people who suffer from schizophrenia. This symptom usually involves hearing voices that the hallucinator firmly believes originate from other people. The voices are often intrusive, abusive and persecutory. They are a source of significant stress and may result in self harm or harm to others. Our investigations will attempt to provide experimental support for the theory that AHs represent a misremembering of voices which were heard in the past. We will do this by attempting to characterise specific problems that hallucinators have in identifying when they heard verbal fragments and who said them. We plan to conduct our investigations at five levels. First, we will determine how accurate hallucinators' memories are for context by the use of special neuropsychological tests. Second, we will find out if hallucinators form more false memories than comparison subjects using a test in which such incorrect recollections occur commonly. Third, we will determine if hallucinators have a tendency to reconstruct the characteristics of false verbal memories in the same way that they reconstruct the characteristics of their hallucinations. Fourth, we will attempt to suppress these false verbal memories and finally, we will characterise those brain regions which are activated during true and false memory formation by using blood flow analysis technology in order to identify networks of brain activity which preferentially malfunction in hallucinating patients. This study provides the prospect of adding substantially to our understanding of the mechanisms underlying auditory hallucinations and to lead to the development of new cognitively-based treatments for the symptom.Read moreRead less
Abeta Amyloid Imaging In Neurodegenerative Disorders With A Novel 18F Radiotracer
Funder
National Health and Medical Research Council
Funding Amount
$1,084,266.00
Summary
Alzheimer's disease is the most common age-related neurodegenerative disease, and the most common cause of dementia. It is estimated that 212,000 Australians suffer from dementia and this will rise to approximately 730,000 by 2050. Currently there are no definitive diagnostic methods for AD. The research proposed in this application describes the evaluation of a new imaging radiotracer that would be suitable for widespread non-invasive diagnosis of AD.
A new scan called PiB PET shows the build up of amyloid protein deposits in the brain in all patients with Alzheimer's disease (AD) but also in 30% of normal elderly persons. This study will track the build up of amyloid and clinical progress in 280 elderly Australians to confirm that this scan can detect AD before symptoms and investigate factors that influence this build up and its damaging effects on memory and thinking. Early detection of Alzheimer's disease will assist accurate diagnosis an ....A new scan called PiB PET shows the build up of amyloid protein deposits in the brain in all patients with Alzheimer's disease (AD) but also in 30% of normal elderly persons. This study will track the build up of amyloid and clinical progress in 280 elderly Australians to confirm that this scan can detect AD before symptoms and investigate factors that influence this build up and its damaging effects on memory and thinking. Early detection of Alzheimer's disease will assist accurate diagnosis and the development of treatment.Read moreRead less
Structural And Functional Consequences Of A Human Nicotinic Receptor Mutation
Funder
National Health and Medical Research Council
Funding Amount
$112,809.00
Summary
Identification of the defective gene underlying a particular form of inherited epilepsy in man, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), now provides the first opportunity to study the basic mechanisms of an inherited epilepsy in man. The responsible mutations affect a subunit of the nicotinic acetylcholine receptor. In this research project, quantitative methods of imaging the brain will be used bridge the gap in understanding which lies between the molecular defect and the ....Identification of the defective gene underlying a particular form of inherited epilepsy in man, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), now provides the first opportunity to study the basic mechanisms of an inherited epilepsy in man. The responsible mutations affect a subunit of the nicotinic acetylcholine receptor. In this research project, quantitative methods of imaging the brain will be used bridge the gap in understanding which lies between the molecular defect and the clinical manifestations of ADNFLE. Involvement of a system of nerve pathways, the mesocortical dopaminergic system, is postulated to explain the preferential susceptibility of the frontal lobe to seizures in ADNFLE. Positron emission tomography will be used to examine changes in neurotransmitter release in the frontal lobe. The molecular defect in ADNFLE also provides a unique opportunity to examine the role of the nicotinic receptor in the development of the human brain and in important aspects of human cognition. Statistical mapping of anatomical variability and high resolution magnetic resonance scans will be used to detect alterations in the anatomical structure of the mesial frontal lobe. Evidence of deficient nicotinic receptor-mediated cognitive effects in ADNFLE will be sought using a battery of psychological tests shown to be sensitive to the effects of nicotine.Read moreRead less
Mechanisms Of Uptake Of 18F-FDG In An In Vivo Model Of C-kit Induced Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Recent advances in the field of tumour biology have created strong interest in development of molecularly targeted anti-tumour drugs. These targeted drugs are expected to yield higher therapeutic indices with fewer side effects than conventional cytotoxic treatments. However, due to the complicated nature of cellular processes affected by a given treatment, and the high cost of bringing new drugs to the clinic, it is important to define both mechanisms of action and in vivo functional effects of ....Recent advances in the field of tumour biology have created strong interest in development of molecularly targeted anti-tumour drugs. These targeted drugs are expected to yield higher therapeutic indices with fewer side effects than conventional cytotoxic treatments. However, due to the complicated nature of cellular processes affected by a given treatment, and the high cost of bringing new drugs to the clinic, it is important to define both mechanisms of action and in vivo functional effects of targeted therapies early in the drug development process. Gastrointestinal stromal tumour (GIST) is a prime example of a cancer for which a rationally designed drug has been successfully used. GISTs are often associated with activating mutations in c-kit, a gene encoding a cell surface protein. A new drug, Imatinib, inhibits the activity of mutated c-kit and blocks growth of many GISTs. However, over time many GISTs become resistant to Imatinib creating the need to develop additional treatments. Unfortunately, this has been hampered by lack of both a good model system for testing new drugs and robust diagnostic procedures for defining response to treatment. We have now developed a mouse model of GIST that grows and responds to treatment in a similar manner to human GIST. Furthermore, using imaging technology specifically designed for small animal studies, we can quickly monitor and evaluate changes in response during treatment. We propose to use the model system together with small animal imaging technology to define mechanisms by which GISTs respond or become resistant to Imatinib. This involves defining specific molecules within cells that change activity after Imatinib treatment as well as testing a series of gene mutations that may be involved in drug resistance. The results of the study will help to define new targets for GIST treatment as well as validate the imaging strategy that may have wide application to monitoring targeted anti-cancer therapies.Read moreRead less