Читать книгу Vestibular Disorders - Группа авторов - Страница 32

High resolution MR imaging has an advantage over all types of CT imaging of the temporal bone as it provides better characterization of soft tissue and fluid-filled partitions. Despite several advantages, the major limitations of this method are the lack of bony details. Even with the recently developed ultra-short echo time pulse sequence, middle ear ossicles are only partly visualized (Naganawa et al. [53], 2016). This is due to the lack of water-containing material in the dense cortical bones. Another major disadvantage of using this method in temporal bone imaging is the high cost of the examination and the sedation needed for younger patients or patients in severe pain. In addition, this method cannot be used for implant imaging or intra-operative imaging where metal objects are involved in the operations as the superconducting magnets attract metals and electronic devices. For patients who are allergic to certain contrast agents, another type of contrast agent that may be more costly is required.

Fig. 3. Endolymph and perilymph in the inner ear. (a) Normal, (b) endolymphatic hydrops. The endolymph (gray) is surrounded by the perilymph (black) except for endolymphatic duct (ED) and endolymphatic sac (ES). U, utricle; S, saccule; St, stapes; R, round window. With permission of Auris Nasus Larynx [70].

MRI is the modality of choice when investigating the inner ear and suspecting soft tissue growth such as vestibular schwannoma, vascular malformations, endolymphatic hydrops or pathology of the cochlear aqueduct [54]. Naganawa et al. [55–57] developed specific algorithms using Fluid Attenuation Inversion Recovery sequences (FLAIR) that will demonstrate minute amounts of contrast agent in the inner ear [56, 58]. The use of MRI in temporal bone imaging is dependent on the area to be visualized, the patient’s age, the pathology involved, and its severity level. MRI is the gold standard in radiologic evaluation of soft tissue changes in the temporal bone and may serve as a complementary method when CT is used to characterize the bony structures.

MRI diagnosis of MD has been challenging until recent years [59]. The first efforts to demonstrate visualization of fluid spaces in the inner ear with gadolinium chelate (GdC) were carried out in animal studies by using animal MRI equipment of 4.7 T scanner [60]. After demonstrating the contrast of perilymph, Zou et al. [61, 62] were the first to demonstrate that endolymphatic hydrops could be visualized accurately in the guinea pig and that the changes were in accordance with the histological verification of the degree of endolymphatic hydrops. These findings were followed by Niyazov et al. [63] who showed similar results using a clinical 1.5 T machine. In humans using 1.5 T MRI, the passage of GdC delivered transtympanically was shown to accumulate in the inner ear after 12 h post injection and fully contrasted the labyrinth after 24 h post injection. However, 1.5T MRI equipment was not sensitive enough to demonstrate the delicate details of the perilymph and endolymph borders [64]. Figure 3 demonstrates the cochlear fluid spaces and endolymphatic hydrops [59].

The recent development of 3T MRI provides a tool for visualizing endolymphatic hydrops with GdC as the contrast agent [65–67] (Fig. 3). MRI, especially in Japan, Germany and more recently in USA has become a clinically useful tool for the diagnosis of atypical and typical cases of MD. Methodological development in imaging techniques and increase of the magnetic field strength have allowed separation of bone from fluid and contrast agent, and have improved spectral resolution, signal-to-noise ratio and contrast intensity, and reduced scan acquisition times [55, 56, 68]. These properties are particularly helpful in resolving details between the minute fluid-filled spaces within the inner ear (approximately 50 µL for endolymph and 150 µL for perilymph!).

A grading scale for the degree of endolymphatic hydrops has been proposed for use in research settings that was validated using identical histologic criteria and has also been applied for clinical evaluations [61, 69, 70]. The normal limit of ratio of the endolymphatic area over the vestibular fluid space (sum of the endolymphatic and perilymphatic area) is 33% and any increase in the ratio would be indicative of endolymphatic hydrops [70, 71]. According to the criteria, mild endolymphatic hydrops in the vestibule cover the ratio of 34–50% and significant endolymphatic hydrops cover the ratio of more than 50% in the vestibule [70]. The respective evaluation of the ratio of the endolymphatic area over the total fluid space in the cochlea is correlated to the displacement of Reissner’s membrane. Normally, the Reissner’s membrane remains in situ and is shown as a straight border between the endolymph-containing scala media and the perilymph-containing scala vestibuli. Mild endolymphatic hydrops display an extrusion of the Reissner’s membrane towards the scala vestibuli and result in an enlargement of the scala media with an area of less than that of the scala vestibuli. Severe endolymphatic hydrops cause an increase of the scala media with an area larger than that of the scala vestibule [70]. A similar grading system on the ordinal level, with three degrees of severity for cochlear hydrops (mild, marked, extreme), has also been proposed [72]. In cadavers without symptom history, the ratio of the endolymphatic space to the total vestibular fluid space ranged from 26.5 to 39.4% [70, 73].

The perilymphatic space facing the vestibule is sealed by the annular stapedial ligament and the perilymphatic space of scala tympani is sealed by the round window membrane. Animal and human experiments indicate that on MRI the perilymphatic space in the vestibule is filled with GdC earlier and more intensively than the perilymphatic space of scala tympani [74, 75]. Thus, the cochlear perilymph space was often poorly filled with GdC than the vestibular part. Zou et al. [76–78] performed a series of experiments by sealing either the round or oval windows and demonstrated that the permeability of the round window was poorer than that of the oval window. This also explains why the treatment of severe MD with low dose gentamicin infrequently causes deafness (less than 5% with two gentamicin injections) [79, 80] but is effective in ablation of vestibular complaints. For the visualization of inner ear membranes, therefore, it is important to fill the upper posterior part of the middle ear cavity with GdC so that the contrast agent has the possibility to be transported also via the oval window as the annular ligament is quite porous. Intratympanic administration of GdC provided efficient loading of the contrast agent in the inner ear perilymph and reduced the risk of systemic toxicity but raised concerns of local toxicity, as it is off label and requires puncture of the tympanic membrane. Such local toxicity was not observed during short, medium or long-term follow-up [81–83]. In addition, image quality might be compromised owing to impaired GdC penetration of the round and oval window membranes [78, 84] and only the injected side of the inner ear can be evaluated [58]. To evaluate both ears simultaneously, it is necessary to inject GdC into both sides [68, 85, 86]. These drawbacks hinder the widespread use of this procedure [87]. The development of more sensitive MRI techniques facilitates endolymphatic hydrops imaging using a single dose of intravenous GdC [56, 88]; this method is intensively used as a clinical research method [89–91]. To establish the normal range of endolymph ratio, healthy volunteers were scanned after intratympanic [70, 73] and intravenous [92] GdC applications. Figure 4 demonstrates the visualization of endolymphatic hydrops with different MRI protocols. Figure 5 demonstrates a combined use of intratympanic GdC in right side and intravenous GdC in the a patient with Meniere’s disease with affected right side to allow comparison between both ears and contrasting of GdC in both inner ears.

Fig. 4. A 72-year-old man with the clinical suspection of left Meniere’s disease. Images are obtained 4 hours after IV-SD-GBCM. Conceptual diagram for the image generation of HYDROPS-Mi2 and HYDROPS2-Mi2. Upper row images indicate the generation of HYDROPS-Mi2. HYDROPS image, which is the subtraction of positive endolymphatic image (not shown) from positive perilymphatic image (heavily T2-weighted 3D-FLAIR, not shown) is multiplied by T2-weighed MR cisternography. Note that black areas (arrows) represent endolymphatic space in labyrinth and white areas represent perilymphatic space on HYDROPS-Mi2. Contrast between endo- and perilymphatic space is very strong, while the back ground signal is quite uniform on HYDROPS-Mi2. Lower row images indicate the generation of HYDROPS2-Mi2. HYDROPS2 image, which is the subtraction T2-weighed MR cisternography from positive perilymphatic image (heavily T2-weighted 3D-FLAIR, not shown) is multiplied by T2-weighed MR cisternography. Note that black areas (arrows) represent endolymphatic space in labyrinth and white areas represent perilymphatic space on HYDROPS2-Mi2 similar to HYDROPS-Mi2. Contrast between endo- and perilymphatic space is very strong, while the back ground signal is quite uniform on HYDROPS2-Mi2 similar to HYDROPS-Mi2. With permission of Jpn J Radiol [58].

The measurement of endolymph volume ratio following 3D-real inversion recovery images obtained 24 h after intratympanic GdC using machine learning and automated local thresholding segmentation algorithms has been reported with highly reproducible results and a highly significant correlation between hearing loss and cochlear endolymphatic hydrops [93]. Semi-automated volume ratio measurement of endolymph from images obtained 4 h after single dose intravenous GdC using short (8 min) and long (18 min) acquisition times [57] has been recommended. The correlation of the volume ratio between the long and short acquisition time images was high, ranging from 0.77 (endolymphatic hydrops in the cochlea) to 0.99 (endolymphatic hydrops in the vestibule); the Pearson’s correlation coefficients were all statistically significant (p < 0.001). Later they demonstrated that 3-Inversion-recovery turbo spin echo with real reconstruction (3D-real IR) showed higher contrast between the non-enhanced endolymph and the surrounding bone [94] (Fig. 6). Regular contrast 3D-FLAIR cannot readily visualize cochlear hydrops after single dose IV-Gd, especially in apical turn. Recently, Naganawa et al. [85, 95] developed the positive endolymph image method, which visualizes endolymph as both a bright signal and subtraction image (HYDROPS images, HYbriD of reversed image of positive endolymph signal and native image of positive perilymph signal images) and allowed more easily interpretable images. In our experience, using heavily T2-weighted 3D-FLAIR positive perilymph image and positive endolymph image and subtracted images (HYDROPS technique) are useful to compensate for the lower concentration of Gd by IV. A further developed technique for generating improved HYDROPS (i-HYDROPS) images allows for a higher contrast to noise ratio per unit time compared to conventional HYDROPS imaging; this is accomplished by elongating the repetition time and increasing the refocusing flip angle [96]. In the study, the size of the endolymphatic space was comparable in both i-HYDROPS and 3D-real IR images. The 3D-real IR does not require post-processing for subtraction and might be more robust towards slight compositional alterations in endolymph than i-HYDROPS imaging based on magnitude reconstruction, and the scan time for 3D real IR images was 10 min.

Fig. 5. A 42-year-old man with a clinical diagnosis of definite Ménière’s disease of the right ear. Images were obtained 24 h after IT-Gd in the right ear and 4 h after IV-SD-GBCM. The right ear shows the combined IT + IV effect while the left ear shows only the IV-Gd effect. Note that only on the IT + IV side is the conventional 3D-FLAIR and 3D-real IR sufficient to show enhancement of the perilymph in order to distinguish the endolymphatic space; however, heavily T2-weighted 3D-FLAIR and HYDROPS2 allows the differentiation between the perilymphatic and endolymphatic space in both the IV side and IT + IV side. Significant endolymphatic hydrops (arrows) is seen in both the cochlea and vestibule on the right side, but no endolymphatic hydrops is observed in the left cochlea. Absence of endolymphatic hydrops in the left vestibule is confirmed in lower-level slices (not shown). With permission of Jpn J Radiol [58].

Fig. 6. 3D Real reconstruction inversion recovery MRI of the right ear illustrates high signal-to-noise ratio and severe cochleovestibular endolmyphatic hydrops in a patient with Ménière’s disease 24 hours after intratympanic GdC application (Magnevist 1:8 diluted). Section thickness 0.3 mm. Siemens Verio scanner, 32-channel head coil. Endolymph appears black, perilymph appears white, temporal bone appears grey. The sections are positioned from left to right and from top to bottom so that they move through the inner ear in a caudal-to-cranial direction. The cochlea displays endolymphatic hydrops in all three turns. The vestibulum displays severe endolymphatic hydrops, with only a weak perilymph signal at its outer borders. The horizontal semicircular canal is completely visualized by its perilymph signal. (With kind permission of Prof. B. Ertl-Wagner, Institute of Clinical Radiology, University of Munich).

Figure 4 (after intravenous injection of GdC) and Fig. 5 (after intratympanic injection plus intravenous injection of GdC) demonstrates the inner ear fluid compartments, anatomical structures and endolymphatic hydrops. Nakashima et al. [59], Pyykko et al. [71], and Fiorino et al. [97] demonstrated, with MRI, that endolymphatic hydrops was present in all living patients with definite MD, which is different from the reports by Shi et al. [98] in which endolymphatic hydrops was absent in some definite MD. Recently, it has been demonstrated that endolymphatic hydrops can affect the cochlear and vestibular compartments differently and cause different complaints [71]. However, the association between clinical symptoms and endolymphatic hydrops in individual patients is not yet clarified, as hearing can be relatively well preserved 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