contrast agents. It is possible that specific molecular MRI and MDCT imaging can be performed after single injection of the targetable dual contrast agent in future.
Targeted Contrast Agents
Contrast agents to enhance or darken fluid or tissue signals help to visualize regions of interest, and efforts are now being made to create biological tags using these agents for molecular imaging at the level of cellular processes. Aimed to visualize liposome NPs in the inner ear, GdC-encapsulated liposomes were developed and distribution of the NPs in the cochlea was detected in vivo using MRI after either intracochlear injection or intratympanic injection [129–131]. These studies open a window in specific visualization of inner ear pathology using MRI. GdC-encapsulated liposomes pass through both the oval and round windows and were not toxic in in vivo experiments. Potential molecular imaging in the inner ear using the novel CAN-γ-Fe2O3 NPs was also demonstrated in an animal study [132]. The novel NPs are especially useful for molecular imaging of the inner ear to detect molecular changes in pathological conditions.
Microtomography
In CT, the cochlear partition and soft tissue as membranes are not adequately visualized [10, 11]. The gray levels in a CT slice image correspond to X-ray attenuation, which reflects the proportion of X-rays scattered or absorbed as they pass through each voxel, and is affected by the density and composition of the material being imaged. Non-destructive X-ray μCT has proven its utility in 3D assessment of mineralized and soft tissue morphology [133, 134]. The cochlear partition and the basilar membrane could not be distinguished and reconstructed with µCT [134]. Recently, Poznyakovskiy et al. [135] presented an algorithm for cochlear segmentation, which resulted in the reconstruction of scala tympani. µCT has been engaged in middle and inner ear imaging of animals and implicated to be a useful tool to trace the distribution of drugs in the inner ear. However, it can only be used for ex vivo imaging due to the extremely high dose of exposure and the close imaging distance which is only suitable for the head [136]. The contrast-enhanced μCT methodology is further developed for ex vivo cochlear imaging [28]. It can demonstrate the position of Reissner’s membrane and basilar membrane if a contrast agent is used [136]. Figure 8 demonstrates CI electrode imaged with μCT. However, μCT produces extremely high radiation dose and in present form cannot be applied in humans.
Recently, this technique has been advanced in animal experiments by revealing the inner ear compartment with simultaneous 9T MRI scanner and μCT [2]. The combined MRI-µCT imaging techniques were complementary, and provided high-resolution dynamic and static visualization of the morphological features of the normal mouse inner ear structures.
Fig. 8. Imaging of CI electrode with µCT, a shows the basal electrodes stimulating areas close to the round window, b shows the first and second tip electrodes aimed to stimulate the apex of the cochlea.
High-Resolution CARS
Raman spectroscopy is a powerful tool to generate a characteristic signature of specific tissues and operates by detecting energy with the molecular bond vibration of incident photons. The process results in non-elastically scattered light, also known as Raman scattering [137]. Raman spectroscopy is capable of discerning molecular pathology of differential proliferative middle ear lesions and may help in the assessment of borders of the pathological process to improve the surgical outcome of the middle ear diseases [7, 138–141]. CARS occurs when a target molecule is irradiated using 2 laser beams simultaneously at different frequencies, a pump beam and a Stokes beam. When the difference between the higher frequency (pump beam) and the lower frequency (Stokes beam) equals the vibrational frequency of the target bond of the molecule, a CARS signal is generated [139–141]. Zou et al. [7] has recently demonstrated the feasibility of using CARS microscopy to display the specific molecular morphology of cholesteatoma that has the potential to be integrated in a novel endoscope for cholesteatoma imaging in the clinic. There are reports on developing CARS endoscopes, although the system needs further improvement [142, 143].
Conclusions
Temporal bone imaging should be sensitive enough to reveal functional disorders after trauma, inflammatory diseases, space occupying lesions such as cholesteatoma or vestibular schwannoma, changes in bone density such as otosclerosis, disruption of ossicular chain, various congenital anomalies, vascular malformations and position and insertion depth of cochlear implants. MDCT and CBCT have the benefit that they accurately describe the bony structures of the temporal bone. During CBCT imaging, the dose is applied to a very narrow section of the body with minimum exposure of the non-targeting area to radiation, and the total X-ray dose is lower compared with MDCT. In addition, CBCT’s rapid data acquisition means that only a low dose of radiation is created during the imaging. MRI, especially at a field strength of 3T, is excellent in revealing changes of the soft tissues and fluid spaces in the temporal bone. The 3T MRI allows relatively accurate visualization of endolymphatic hydrops and even the membranous structures of the inner ear. Modern trends with targeted imaging of the inner ear may provide possibilities to visualize inner ear pathologies that can be assessed today only on histology. The recent imaging possibilities to explore inner ear fluid spaces are especially encouraging and contribute to clinical practice by defining Hydropic Ear Disease as a new entity.
References
1DeMarcantonio M, Choo DI: Radiographic evaluation of children with hearing loss. Otolaryngol Clin North Am 2015;48:913–932.
2Counter SA, Damberg P, Aski SN, Nagy K, Berglin CE, Laurell G: Experimental fusion of contrast enhanced high-field magnetic resonance imaging and high-resolution micro-computed tomography in imaging the mouse inner ear. Open Neuroimag J 2015;9:7–12.
3Pitris C, Saunders KT, Fujimoto JG, Brezinski ME: High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study. Arch Otolaryngol Head Neck Surg 2001;127:637–642.
4Lin