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Scheme : NHMRC Development Grants
Research Topic : post-mortem brain tissue
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  • Funded Activity

    Assessment Of Bilateral Oedema By Bioelectrical Impedance Analysis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $180,000.00
    Summary
    Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estima .... Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estimated that at any time 100000 women are suffering from post- mastectomy lymphedema in Australia alone. Treatment of breast cancer alone therefore, given the incidence of the disease, produces a large at-risk population. Add to this other causes of oedema and the magnitude of the problem becomes clearly apparent. The presence of chronic oedema is often a disfiguring and disabling disorder, usually accompanied by pain, recurrent infection, reduced mobility and impaired function. In acute oedema the problem often resolves with recovery from the underlying pathology. In chronic oedema, progression may be arrested by early intervention including complex physical therapy (exercise regimen, compression bandaging, and massage) which is effective in reducing limb volume, in improving the quality of life, function and body image of patients. Although the assessment of oedema is clearly of clinical importance, relatively few objective and accurate techniques for its measurement exist. Research conducted over the past decade by the applicants has pioneered the Use of Bioelectrical Impedance Analysis for the assessment of lymphedema. This study aims to translate this basic research into clinical practice. Sensitivity and specificity studies will establish normative and threshold values for impedance measurements that can be used as presumptive indicators of oedema. User friendly technology and equipment suitable for clinical use will be developed which should improve treatment therapies.
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    Funded Activity

    Commercial Testing Of A Physiologically Based Theory Of Oscillatory Brain Electrical Activity In Anaesthesia Monitoring

    Funder
    National Health and Medical Research Council
    Funding Amount
    $191,165.00
    Summary
    While the mechanisms of local anaesthesia are comparatively well known, the mechanisms whereby anaesthetics impair consciousness remain unresolved. This lack of understanding has implications in our ability to monitor the level of anaesthesia while anaesthetic consumption and side effects are minimized. Despite this a number of devices have been developed that attempt to monitor the depth of anaesthesia by quantifying the brains electrical activity. All monitors analyse the activity using a set .... While the mechanisms of local anaesthesia are comparatively well known, the mechanisms whereby anaesthetics impair consciousness remain unresolved. This lack of understanding has implications in our ability to monitor the level of anaesthesia while anaesthetic consumption and side effects are minimized. Despite this a number of devices have been developed that attempt to monitor the depth of anaesthesia by quantifying the brains electrical activity. All monitors analyse the activity using a set of criteria that have been developed by trial and error. The research of Dr David Liley and his team, at Swinburne University of Technology, has resulted in a detailed understanding of the physiological mechanisms that generate brain electrical activity. The outcome is a practical means to carry out a System Based Analysis of Brain Electrical Response (SABER). In 2004, Dr Liley began working with Cortical Dynamics, a company involved in the commercialisation of medical devices. This collaboration incorporated the SABER system into a new prototype device called the Brain Anaesthesia Response (BAR) monitor. In 2004 Dr Liley and Associate Professor Kate Leslie collaborated in a trial, at the Royal Melbourne Hospital to test the sensitivity of the SABER system in quantifying the effect that various levels of nitrous oxide have on measures of anaesthetic depth. The Australian and New Zealand College of Anaesthetists supported this study. Initial results obtained with sevoflurane and 3 levels of nitrous oxide showed the ability to differentiate between conscious and unconscious states of patients based on two physiological characterizations of higher brain dynamic state. The next step requires commercial product validation (ie scale up) and further clinical efficacy in testing beta stage depth of anaesthesia BAR units. Completion of this will help the technology move away from a low volume prototype system into a commercially applicable device.
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    Funded Activity

    Development And Pre-Clinical Evaluation Of A Silicone Dressing For Scar Remediation

    Funder
    National Health and Medical Research Council
    Funding Amount
    $163,577.00
    Summary
    This research is aimed at exploiting advanced polymers as a new therapy for patients with burn related scars, as well as people who are genetically predisposed to scarring due to abnormal healing. In order to progress to clinical trials, the technology needs to be tested on an animal scar model. Successful outcome of these tests will allow the industry partner, Tissue Therapies, to proceed with a clinical trial, paving the way to a therapeutic product available for scar treatment.
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    Funded Activity

    Development Of A PET Detection System Prototype With Depth Of Interaction Capability

    Funder
    National Health and Medical Research Council
    Funding Amount
    $360,906.00
    Summary
    This development project invovles the development of a slim-line Positron Emission Tomogrphy (PET) detection sub-module, the crucial component of PET scanners, that is small and extremely flexible. It is planned to utilize this module in the design of customized new commercial PET scanners ideal for diagnosing human brain and breast disorders. The development will proceed in collaboration with Insight Oceania-ADAC, Sydney. Insight Oceania-ADAC are very excited by the potential applications and f .... This development project invovles the development of a slim-line Positron Emission Tomogrphy (PET) detection sub-module, the crucial component of PET scanners, that is small and extremely flexible. It is planned to utilize this module in the design of customized new commercial PET scanners ideal for diagnosing human brain and breast disorders. The development will proceed in collaboration with Insight Oceania-ADAC, Sydney. Insight Oceania-ADAC are very excited by the potential applications and future markets (Australia and overseas) of the newly developing PET detection sub-modules for dedicated PET scanners. Positron Emission Tomography (PET) is a functional imaging tool, which is able to quantify physiological and biochemical processes in vivo, using short-lived cyclotron-produced radiotracers. PET is emerging as an extremely important diagnostic procedure used in the early detection of cancers, neurological diseases and as an aid in treatment monitoring and drug development. The unique advantage of PET over anatomical imaging techniques, such as X-ray CT and MRI, arises from its ability to measure changes in tumour biology, at the molecular level, prior to anatomical changes in involved tissues, using trace amounts of a radiolabelled compound (radiotracer). The full potential of PET however, is not being completely utilized due to constraints within the current designs of PET scanners. When used to its full potential PET, in principle, would be an excellent diagnostic and treatment monitoring tool for breast cancer, brain tumours and other neurological conditions such as epilepsy, Alzheimer's, Parkinson's disease, post stress disorder, dementia, and depression. Lack of flexibility in current PET scanner designs to date has meant that no commercial human brain or breast imaging scanners exist. Pilot project data proved the feasibility of our new flexible PET detection module design.
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    Funded Activity

    Se015: A Developmental Drug For The Treatment Of Brain Tumours

    Funder
    National Health and Medical Research Council
    Funding Amount
    $304,206.00
    Summary
    Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with .... Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with disease progression. Nearly all therapies that have shown some efficacy in treating cancer, such as chemotherapy and radiation have a mode of action whereby they attempt to kill cancer cells by inflicting enough damage to the cancer cells that they induce them to commit cell suicide, a process called apoptosis. Unfortunately, cancer cells can become resistant to these therapies by activating the cells' own signaling pathways that normally block apoptosis. One of the key pathways that has been implicated in resistance to apoptosis in human cancers is the PI3K-Akt pathway. This pathway is overactivated in many advanced human tumors, particularly in glioblastoma. We have discovered a compound, Se015, which can effecitively block this pathway in brain cancer cells and is able to dramatically improve the effectiveness of both chemotherapy and radiation in killing these cells. We have confirmed the efectiveness of Se015 in preliminary animal models of brain cancer, where we have shown that Se015 demonstrated no noticeable toxicity and was active when taken orally. We now need to explore further the molecular mode of action of Se015, as well as complete our animal studies with the eventual aim of initiating a small trial of Se015 in glioblastoma patients in the forseeable future.
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    Funded Activity

    Development And Pre-clinical Evaluation Of A Novel Wound Dressing Treatment For Chronic Ulcers

    Funder
    National Health and Medical Research Council
    Funding Amount
    $125,040.00
    Summary
    Chronic leg ulcers are a common, painful and costly reality for many Australians, impacting on sufferers' mobility, social interactions and overall quality of life. This research is directed at developing a novel cost-effective wound dressing for treatment of this condition. This will be achieved through neutralising the ulcer's toxic proteolytic environment through an interactive wound dressing. This then will allow the body's own cells to promote wound healing.
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    Funded Activity

    Automated Seizure Detection In The Newborn.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $243,750.00
    Summary
    Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertake .... Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertaken. We anticipate that the product will be of major commercial interest. We will further explore what is a rapidly expanding marketplace and ensure we maximize the commercial return on this product.
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    Funded Activity

    A Motion Correction Technique For Accurate PET/CT Brain Imaging In Paediatric And Dementia Patients

    Funder
    National Health and Medical Research Council
    Funding Amount
    $190,450.00
    Summary
    PET-CT imaging is a vital tool in the diagnosis and management of patients with brain disorders including dementia, epilepsy and cancer. However images are often distorted by patient motion, particularly in demented and paediatric patients. The CI has recently developed a motion tracking and correction method to derive images nearly free of motion effects. This aim of this project is to evaluate its impact on image quality in a variety of patients referred for PET- CT brain investigations.
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    Funded Activity

    Rapid, Cost-effective, Diagnosis And Monitoring Of Multiple Sclerosis By Novel Multifocal Evoked Potential Methods

    Funder
    National Health and Medical Research Council
    Funding Amount
    $152,463.00
    Summary
    A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increas .... A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increasing disability of MS. MS only affects about 0.04% of Australians but the early onset of MS, the high cost of medication, and the prolonged period of disability, mean that the cost to Australia is about $2 billion pa. MRI quantifies the inflammatory phase well but is poorly correlated with the debilitating secondary progression. The common treatments for MS target the inflammatory phase but not the causes of secondary progression, which are unknown. Current diagnostic methods mean diagnosis can take years, meaning that patients can be denied treatment for some time. The applicants have published experiments on 50 MS patients and 27 normal subjects using a variant of the new method. Not only has it shown high diagnostic accuracy, but the new method seems to provide data on the progressive phase, suggesting strongly that it is complementary to MRI. The new method is also much cheaper to set up and run than MRI and so could provide cost-effective means for monitoring patient condition and testing new drugs that are effective against the progressive phase. The applicants have considerable experience commercialising diagnostic technologies, and are currently working with an Australian company developing new diagnostic hardware. That hardware has been adapted to perform the presently proposed experiments. Overall it is reasonable to assume that positive outcomes will be translated into economic and health benefits for Australians.
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    Funded Activity

    A Device For Simultaneous Continuous Acquisition Of EEG And MRI

    Funder
    National Health and Medical Research Council
    Funding Amount
    $179,401.00
    Summary
    We aim to further develop a world-leading method we invented that facilitates the simultaneous, continuous acquisition of the electroencephalogram (EEG - electrical brain waves measured at the scalp) and functional Magnetic Resonance Imaging (fMRI - images the location of brain activity throughout the brain). Combining the two permits non-invasive imaging of human brain function with the exquisite temporal resolution of EEG and the high spatial resolution and brain coverage afforded by fMRI.
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