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    3 July 2018

  • Learning to identify CNS drug action and efficacy using multistudy fMRI data.

    3 July 2018

    The therapeutic effects of centrally acting pharmaceuticals can manifest gradually and unreliably in patients, making the drug discovery process slow and expensive. Biological markers providing early evidence for clinical efficacy could help prioritize development of the more promising drug candidates. A potential source of such markers is functional magnetic resonance imaging (fMRI), a noninvasive imaging technique that can complement molecular imaging. fMRI has been used to characterize how drugs cause changes in brain activity. However, variation in study protocols and analysis techniques has made it difficult to identify consistent associations between subtle modulations of brain activity and clinical efficacy. We present and validate a general protocol for functional imaging-based assessment of drug activity in the central nervous system. The protocol uses machine learning methods and data from multiple published studies to identify reliable associations between drug-related activity modulations and drug efficacy, which can then be used to assess new data. A proof-of-concept version of this approach was developed and is shown here for analgesics (pain medication), and validated with eight separate studies of analgesic compounds. Our results show that the systematic integration of multistudy data permits the generalized inferences required for drug discovery. Multistudy integrative strategies of this type could help optimize the drug discovery and validation pipeline.

  • Neuroimaging as a tool for pain diagnosis and analgesic development.

    3 July 2018

    Neuroimaging makes it possible to study pain processing beyond the peripheral nervous system, at the supraspinal level, in a safe, noninvasive way, without interfering with neurophysiological processes. In recent years, studies using brain imaging methods have contributed to our understanding of the mechanisms responsible for the development and maintenance of chronic pain. Moreover, neuroimaging shows promising results for analgesic drug development and in characterizing different types of pain, bringing us closer to development of mechanism-based diagnoses and treatments for the chronic pain patient.

  • Measurement of brain temperature with magnetic resonance spectroscopy in acute ischemic stroke.

    28 June 2018

    OBJECTIVE: Pyrexia is associated with poor outcome after stroke, but the temperature changes in the brain after stroke are poorly understood. We used magnetic resonance spectroscopic imaging (water-to-N-acetylaspartate frequency shift) to measure cerebral temperature noninvasively in stroke patients. METHODS: We performed magnetic resonance diffusion, perfusion (diffusion- and perfusion-weighted imaging), and magnetic resonance spectroscopic imaging, compared temperatures in tissues as defined by the diffusion-weighted imaging appearance (definitely abnormal, possibly abnormal and immediately adjacent normal-appearing brain, and normal brain), and tested associations with lesion and patient characteristics. RESULTS: Among 40 patients, temperature was higher in possibly abnormal (37.63 degrees C) than in definitely abnormal tissue (37.30 degrees C; p < 0.001) or in normal-appearing brain (ipsilateral, 37.16 degrees C; contralateral, 37.22 degrees C; both p < 0.001). Ischemic lesion temperature increased before normal brain temperature. Higher temperatures occurred in lesions that were large, had diffusion/perfusion-weighted imaging mismatch, had reduced cerebral blood flow, and in clinically severe strokes. Only 1 of 25 patients with ischemic lesion temperature greater than 37.5 degrees C was pyrexial. INTERPRETATION: Temperature is elevated in acutely ischemic brain. More work is required to determine whether raised temperature results from ischemic metabolic reactions, impaired heat exchange from reduced cerebral blood flow, or early inflammatory cell activity (or a combination of these), but magnetic resonance spectroscopic imaging could be used in studies of temperature after brain injury and to monitor interventions.

  • Histology information

    8 October 2015

  • Inflammatory Arthritis Microbiome Consortium

    15 May 2017

    Bacteria and other microorganisms of the intestinal tract (collectively known as the gut microbiota) have fundamental roles in maintaining a healthy immune system. The ultimate goal of the Inflammatory Arthritis Microbiome Consortium (IAMC) is to manipulate the human microbiota for the treatment of inflammatory arthritis.

  • Inflammatory Arthritis Microbiome Consortium

    11 November 2015

    Kennedy Institute leads international consortium to investigate the link between gut bacteria and arthritis.

  • Homepage

    2 July 2015

  • A New Location

    15 May 2017

    As part of its relocation to Oxford the Kennedy Institute moved to a new £34 million purpose-built building located on the University Old Road Campus in 2013.

  • Events

    14 December 2015

  • Contact Us

    11 October 2015

  • About the Kennedy Institute

    1 January 2012

    The Kennedy Institute of Rheumatology is a world-leading medical research centre where discovery research drives development of transformative therapies for chronic inflammatory and degenerative disease.

  • External DPhil programmes

    15 October 2015