despite prominent endolymphatic hydrops [67, 99] and the extent of endolymphatic hydrops seems to vary along the course of the disease: it may increase, decrease or remain stable [100–102]. With new imaging techniques, endolymphatic hydrops can be demonstrated in vivo and can confirm the diagnosis. Furthermore, it has become possible to evaluate MD using new functional tests, such as VEMP frequency tuning measurements, in patient populations with clinically and morphologically (by MRI detection of endolymphatic hydrops) confirmed diagnosis of MD [101, 103].
The current challenges in inner ear imaging are to improve the delivery of the contrast agent so that the concentration of GdC in the inner ear exceeds the detection limit. The transtympanic and intravenous administrations have different indications [66]. If the aim is to demonstrate endolymphatic hydrops, then transtympanic injection of GdC is preferred. Usually the transtympanic administration provides stronger uptake and is easier to assess than intravenous injection. In principle, the sensitivity of the intravenous and the transtympanic method to demonstrate endolymphatic hydrops in the inner ear should be similar based on sufficient uptake of GdC in the inner ear, as both methods measure the same phenomenon [87]. A technique in which the images of inverted grey-scale positive endolymph are subtracted from images with native positive perilymph images is useful when inner ear loading of GdC is low. This subtraction significantly improves the contrast noise ratio and assists in the separation of endolymph, perilymph, and bone [104] or when combining intravenous injection with transtympanic injection [68].
The development of dynamic imaging techniques of the inner ear has provided several important new insights into MD; (1) the cochlear and vestibular compartments can be differently affected and (2) in about 24–75% of the cases the disease is bilateral [71, 105]. (3) The extent of endolymphatic hydrops can vary with time in individual patients [102]. (4) The extent 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
