Vestibular Disorders. Группа авторов

of endolymphatic hydrops does not correlate with complaints [86]. The variable latency between complaints in MD [71] and the bilateral nature of the disease confirms [106, 107] the observations in MRI [71]. Unilateral disease was reported to progress in bilateral disease in up to 35% of patients within 10 years and in up to 47% within 20 years of follow-up [108, 109]. The vestibule showed endolymphatic hydrops more frequently than did the cochlea, although most commonly the endolymphatic hydrops was found in both cochlea and vestibule [71]. Patients with sudden deafness and spontaneous tinnitus often had endolymphatic hydrops [71]. Whether endolymphatic hydrops will develop in all forms of tinnitus is not known but is worth studying. The application of endolymphatic hydrops imaging in patients with various inner ear symptoms and disorders has shown that endolymphatic hydrops is not only present in cases of typical MD, but also in its monosymptomatic variants and in the conditions of secondary endolymphatic hydrops. These observations have coined the term “Hydropic Ear Disease,” allowing for a logic and comprehensive classification of these disorders [110].

Furthermore, clinical imaging of endolymphatic hydrops has shown that (1) endolymphatic hydrops progresses with time, both on the cross-sectional level [72] and on the individual level [101], (2) the severity of cochlear and vestibular function deficits are generally correlated with the severity of endolymphatic hydrops [72], and (3) the hydropic herniation of vestibular endolymphatic spaces into the semicircular canal can be visualized in vivo [111]. The advent of accurate measurements of the vestibulo-ocular reflex (VOR) at high frequencies (Video Head Impulse test) offers a possible explanation for the well-known paradox of horizontal semicircular canal dysfunction in MD: while the (low-frequency) caloric response is impaired, the (high frequency) head impulse test is typically normal [112–114].

In clinical practice, the question “which GdC delivery pathway should be taken – the intratympanic or the intravenous delivery?” often remains unanswered. Table 2 demonstrates the alternative strategies to visualize inner ear disorders in different diseases and suspected pathologies. The benefit of intratympanic delivery is that most often the GdC concentration is greater in transtympanic delivery than in intravenous delivery, and the pathology is easier to assess (Fig. 5). However, even with this delivery route in our hands, occasionally the inner ear shows insufficient concentration of GdC in the perilymph, and hence assessment of the disorder may be difficult.

Table 2. Inner ear pathology with MRI with different application routes of contrast agent used for visualizing different nature of the disorder

      Future Development

      Novel Contrast Agents

Novel, highly sensitive, specific, and low-toxicity contrast agents for MRI and MDCT are the need of the hour in clinics. For MRI, manganese-containing contrast agents would be most suitable as they can demonstrate calcium metabolism that is inherent in disease processes in the inner ear [115–118]. Nanoparticle-based GdC carrier are an effective MRI T1 contrast agent and have been used in high resolution MRI for tracing apoptosis and gene transcription in animal models of cerebral ischemia and brain tumors [119, 120]. A novel, super-paramagnetic iron oxide nanoparticle (SPION) that is water soluble, a characteristic that can be invaluable for medical applications, has been designed (Fig. 7) [121, 122]. It is constructed from iron oxide nanoparticle cores with a hierarchical coating consisting of a surface layer of Pluornic® F127 copolymer (PF127, approved by the Food and Drug Administration) that overlays a layer of oleic acid on the surface of the iron oxide nanoparticles (POA@SPIONs). POA@SPIONs is a promising T2-negative contrast agent that is detectable within the inner ear by MRI [123]. Functionalization of POA@SPIONs can be performed that make it a target for inflammatory cytokines in the inner ear; however, they were found not to enter the inner ear efficiently after the transtympanic injection [106]. Another novel, highly hydrophilic, anti-aggregative super-paramagnetic maghemite (γ-Fe₂O₃) nanoparticle (NP) was developed using ceric ammonium nitrate (CAN)-mediated oxidation of starting magnetite (Fe₃O₄) NPs (CAN-γ-Fe₂O₃ NPs), which were highly stable aqueous suspensions/ferrofluids due to a unique ultrasound-mediated doping process of the Fe₃O₄ NP surface using lanthanide Ce^3/4+ cations [124]. Zou et al. [125] have also demonstrated that the novel CAN-γ-Fe₂O₃ NPs is a strong T₂ MRI contrast agent that penetrates both round and oval windows, and has potential applications in molecular imaging of the inner ear [125].

Fig. 7. Super-paramagnetic iron oxide nanoparticles (SPION) contrasted inner ear in a rat. The SPION administered into the perilymph will extinguish the signal from the perilymph and only endolymphatic spaces are visible on MRI. Reprinted with permission of Europ J nanomed [122]. Cochlea, vestibule and the semicircular canals are shown.

By developing a novel nanomaterial to be used as contrasting agent, for example, encapsulation of metals and metal clusters in fullerenes (endohedral metallofullerenes) opens additional vistas for inner ear imaging [126–128]. The carbon cage has inherent advantages because of its high stability and characteristic resistance to any potential metabolic cage-opening process. This prevents the release of toxic metal ions from endohedral metallofullerenes into surrounding tissue, serum, and other biologic components [126]. Water-soluble endohedral gadolinium-lutetium fullerene is generating considerable interest because of the possibility of using these novel nanomaterials