Markers of cochlear inflammation using MRI

Abstract

Purpose: To quantify spatial and temporal inflammation-induced changes in vascular permeability and macrophage infiltration in guinea-pig (GP) cochlea using MRI. Materials and Methods: GPs were injected with lipopolysaccharide (LPS) to induce cochlear inflammation. One group was injected with a gadolinium based contrast agent (GBCA) and dynamic contrast enhanced (DCE)-MRI was performed at 4, 7, and 10 days after LPS treatment. A two-compartment pharmacokinetic model was used to determine the apparent rate constant of GBCA extravasation (Ktrans). A second group was injected with ultrasmall superparamagnetic iron oxide particles (USPIOs) and studied at 2, 3, and 7 days after LPS treatment to detect tissue USPIO uptake and correlate with histology. For both groups, control GPs were scanned similarly. Results: The signal enhancement increased substantially and more rapidly at day 4 in LPS-treated than in control cochlea shortly following GBCA injection. Ktrans of LPS-treated cochlea was maximum on day 4 at 0.0218±0.0032 min−1 and then decreased to control level at 0.0036±0.0004 min−1 by day 10. In the second group, the relative signal intensity and T2 in cochlear perilymphatic spaces on day 2 decreased, on average, by 54% and 45%, respectively, compared with baseline and then remained under control levels by day 7. This suggests the infiltration of inflammatory cells, although unconfirmed by histology. Conclusion: This provides the first measurement of cochlear vascular permeability using MRI and a quantitative evaluation of the development of cochlear inflammation. MRI holds considerable potential for the assessment of disease processes such as clinical diagnosis of conditions such as labyrinthitis.

The blood labyrinthine barrier in the human normal and Meniere’s disease macula utricle

“…Intratympanic injection of lipopolysaccharide (LPS), a substance that breaks down the BLB and also the BBB, is associated with increased gadolinium perilymphatic enhancement 41 . A similar increase in gadolinium uptake in the perilymph has been noted following high intensity impulse noise acoustic trauma 42 .…”

Pathophysiology of the cochlear intrastrial fluid-blood barrier (review)

“…In particular, dynamic contrast enhanced (DCE) MRI using gadolidium-chelate (GdC) or gadolidium based contrast agents (GBCA) is increasingly being used to assess changes in vascular permeability (Le Floc'h et al, 2014; Walton et al, 2015). Intense noise, inflammation, and immune reactions disrupt the blood-barrier and cause leakage of GdC.…”

“…Intense noise, inflammation, and immune reactions disrupt the blood-barrier and cause leakage of GdC. Using contrast enhanced-MRI and GBCA, lipopolysaccharide (LPS) induced vascular leakage can be assessed in guinea pig (Le Floc'h et al, 2014; Walton et al, 2015). In humans, the technique provides an opportunity to visualize the different cochlear compartments and directly evaluate the integrity of inner ear barriers.…”

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow

“…Direct measurement of CoBF is difficult and techniques for assessing blood flow are still under development. Various methods are used for assessment of CoBF, including laser-doppler flowmetry (LDF), magnetic resonance imaging (MRI), fluorescence intra-vital microscopy (FIVM), fluorescence microendoscopy (FME), as well as approaches based on injection of dye labeled or radioactive microspheres into the blood stream (Angelborg et al, 1988; Choudhury et al, 2010; Larsen et al, 1982; Le Floc'h et al, 2014; Monfared et al, 2006; Nakashima et al, 2002; Reif et al, 2012; Subhash et al, 2011). Approaches such as LDF, MRI, and injection of microspheres into the blood plasma are limited in providing information on relative change in blood flow rather than absolute flow rate in individual vessels.…”