Magnetic Resonance Imaging of Brain Inflammation Using Microparticles of Iron Oxide

Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
Methods in molecular biology (Clifton, N.J.) (Impact Factor: 1.29). 01/2011; 680:103-15. DOI: 10.1007/978-1-60761-901-7_7
Source: PubMed


For molecular magnetic resonance imaging (mMRI), microparticles of iron oxide (MPIO) create potent hypointense contrast effects that extend a distance far exceeding their physical size. The potency of the contrast effects derive from their high iron content and are significantly greater than that of ultra-small particles of iron oxide (USPIO), commonly used for MRI. Due to their size and incompressible nature, MPIO are less susceptible to nonspecific vascular egress or uptake by endothelial cells. Therefore, MPIO may be useful contrast agents for detection of endovascular molecular targets by MRI. This Chapter describes the methodology of a novel, functional MPIO probe targeting vascular cell adhesion molecule-1 (VCAM-1), for detection of acute brain inflammation in vivo, at a time when pathology is undetectable by conventional MRI. Protocols are included for conjugation of MPIO to mouse monoclonal antibodies against VCAM-1 (VCAM-MPIO), the validation of VCAM-MPIO binding specificity to activated endothelial cells in vitro, and the application of VCAM-MPIO for in vivo targeted MRI of acute brain inflammation in mice. This functional molecular imaging tool may potentially accelerate accurate diagnosis of early cerebral vascular inflammation by MRI, and guide specific therapy.

35 Reads
  • Source
    • "Ultra high-field neuroimaging combined with injections of iron oxide nanoparticles is emerging as a neuroimaging method to visualize inflammatory phenomena at the cellular level by marking activated microglia in early inflammatory stages. This method shows greater regional binding of contrast agent even in the absence of frank disruptions to blood-brain barrier permeability and with greater spatial resolution than Gadolinium contrast approaches (see references [57] [58] [59] [60] for reviews). Magnetic resonance molecular imaging has been used in acute ischemic stroke to identify endothelial activation by targeting biomolecular agents [61]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.
    Full-text · Article · Feb 2012 · Aging and Disease
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MRI is an established diagnostic tool, but it also has great attraction for use in experimental research, particularly in neuroscience and neurology. In vivo imaging of specific cell populations in the brain is particularly attractive for furthering understanding of cell behavior in animal models of neurological disease and injury. Approaches towards this end typically make use of iron oxide nanoparticles as MRI contrast agents. These contrast agents can be taken up by peripheral inflammatory cells, by endogenous CNS cell populations, or by in vitro cell cultures for transplantation experiments. Molecular imaging of functional cell status, using MRI in combination with molecular biology, is a rapidly expanding field with great promise. The present review summarizes the current status of cellular MRI in the brain in the context of ischemia models, and relevant issues and approaches that aim to improve translation of cell therapy strategies into the clinic.
    Full-text · Article · Jul 2008 · Future Neurology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the usefulness of a fully flow-compensated heavy T2*-weighted imaging enhanced by superparamagnetic iron oxide (SPIO) particles for distinguishing between focused ultrasound-induced disruption of blood-brain barrier (BBB) and brain hemorrhage. Focused ultrasound (frequency: 1.5 MHz) was used to induce disruption of the BBB in 39 rats. Two T2*-weighted images were obtained before and after SPIO administration. Preenhanced T2*-weighted images were used to detect hemorrhage. Detection of BBB disruption was performed on SPIO-enhanced images. Thirty-four rats were sacrificed after magnetic resonance (MR) scanning for histological confirmation of brain lesions. The remaining five animals were followed up for 35 days. Prussian blue staining was performed on histological sections to detect SPIO particles in the brain. After SPIO injection the areas of BBB disruption in rat brain were significantly enlarged. The area of mismatch between the T2*-weighted images indicated a safe region where BBB opening occurred without hemorrhagic complications. In the longitudinal study, removal of SPIO occurred at a faster rate in hemorrhagic areas, albeit being closer to that occurring in the liver. The presence of SPIO was confirmed by Prussian blue staining in brain parenchyma and capillary endothelial cells in areas of BBB disruption. T2*-weighted images-either with and without SPIO enhancement-may differentiate focused ultrasound-induced BBB disruption from brain hemorrhage.
    Full-text · Article · Jan 2009 · Journal of Magnetic Resonance Imaging
Show more