Markers of cochlear inflammation using MRI

Autor: Beau Pontre, Alfred L. Nuttall, Peter R. Thorne, Johann Le Floc'h, R. S. Telang, Srdjan M. Vlajkovic, Winston Tan, William D. Rooney
Rok vydání: 2013
Předmět:
Zdroj: Journal of Magnetic Resonance Imaging. 39:150-161
ISSN: 1053-1807
DOI: 10.1002/jmri.24144
Popis: HEARING LOSS FROM injury and disease of the auditory sensory organ, the cochlea, affects a large and increasing proportion of the population (1,2). There is a need to understand the mechanisms of cochlear injury to develop targeted treatments for hearing loss. Cochlear degeneration and the associated hearing loss occur from a great variety of causes including genetic abnormalities, aging, noise exposure, drug ototoxicity (e.g., aminoglycoside antibiotics and anti-cancer drugs), trauma, and infection. Inflammation of the inner ear is thought to be a major contributor to the development of cochlear injury and the concomitant sensorineural hearing loss from many different causes, as well as a consequence of inner ear surgery, for example, cochlear implantation (3). Cochlear inflammation caused by middle or inner ear infections, trauma and noise exposure, has been characterized in animal models (4,5). Treatment with steroids, such as dexamethasone, can mitigate the injury and hearing loss in animals (6). Inflammation is also assumed, rather than diagnosed, in many clinical conditions affecting the inner ear, and steroids are the treatment of choice (6). However, there is scarce direct evidence of inflammation occurring in these clinical conditions and very little evidence of the dynamics of the inflammatory responses in the human inner ear (7,8). Understanding the inflammatory processes, and being able to determine its time course and stages in an individual patient, would aid the diagnosis of the type and location of cochlear injury, and lead to the development of targeted treatments to reduce the deleterious effects of inflammation on the delicate structures of the inner ear. The location of inner ear tissues deep within the temporal bone of the skull is a significant impediment to identifying any disease process in the inner ear. This is particularly an issue when investigating or identifying detrimental processes such as inflammatory disease in the human inner ear. The current knowledge of inner ear inflammation mostly stems from animal studies involving tissue collection and histological or molecular analysis of inflammatory markers, whereas little is known about the progression of inflammatory disease in the living inner ear. Recent developments in MRI offer exciting opportunities for studying structure, function and metabolism of the intact, living cochlea. Visualization of cochlear structures in animals and humans can be achieved with high field strength magnets (9-11) as well as some quantification in animals, but these have been limited to the differentiation and quantification of cochlear fluid compartments, and quantification in terms of relative signal intensity of the uptake of gadolinium based contrast agent (GBCA) in some cochlear fluid spaces (12,13). However, all the studies (10,11,14) to date essentially have been qualitative and, very few have looked at the dynamic changes during cochlear inflammation (7,8). MRI has been used clinically in an attempt to assess cochlear disorders (9-11,14,15), particularly the changes in the dimensions of the fluid compartments associated with Meniere's disease and any changes that may underlie sudden sensorineural hearing loss. For the purpose of this study, the dynamic contrast enhanced-MRI technique and macrophage imaging approach using iron oxide particles are of particular interest. Dynamic contrast enhanced-MRI (DCE-MRI) involves the acquisition of a series of T1-weighted images before and after the injection of a paramagnetic contrast agent. The application of a pharmacokinetic (PK) model to these acquired data permits the calculation of meaningful physiological parameters; namely, the volume transfer rate constant of contrast agent extravasation (Ktrans) and the volume fraction of the extravascular, extracellular space (EES, νe) of the tissue of interest. The original DCE-MRI PK model was described more than 10 years ago (16), and numerous alternate models have been described since (17-24). To date however, quantitative DCE-MRI has not been applied to calculate changes in vascular permeability in the normal or diseased inner ear. Macrophage infiltration may be visualized noninvasively by use of superparamagnetic iron oxide nanoparticles which are taken up by the monocyte-macrophage system (25,26) and predominantly affect the transverse relaxation time. These nanoparticles have found many potential medical applications for the detection of diseases involving an inflammatory response (27) and are seen as having a great potential for the assessment of the therapeutic efficacy of inflammatory diseases developing in the central nervous system (28). To date, one specific type of superparamagnetic iron oxide nanoparticle was reported to facilitate the differentiation between the two cochlear fluids when injected directly into the rat cochlea (29). However, there has been no report of their use for the study of cochlear inflammation. Our approach has been to develop MRI techniques to probe inner ear function and to use specific bio-markers of disease processes to qualitatively and quantitatively define the dynamics (admittedly on the relatively long time scale enabled by MRI) and chronic progression of disease processes in an individual. Here we report the use of DCE-MRI and ultrasmall superparamagnetic iron oxide particles (USPIOs) to quantify changes in vascular permeability and to characterize the recruitment of phagocytic cells into the cochlear tissues in a guinea-pig model of inner ear inflammation. This research also provides a translational pathway for cochlear imaging and development of MR as diagnostic tools for human inner ear diseases.
Databáze: OpenAIRE
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