Significance of high signal intensity in the endolymphatic duct on magnetic resonance imaging in ears with otological disorders.

BACKGROUND: High signal intensity in the endolymphatic duct (ED) is occasionally observed on magnetic resonance imaging (MRI) in ears that have otological disorders. OBJECTIVE: The signal intensity (SI) in the ED on post-contrast MRI was investigated in subjects with various otological disorders, and the meaning of high SI in the ED was evaluated. MATERIAL AND METHODS: 392 patients with otological disorders and 21 controls without otological symptoms underwent 3 T MRI. The SIs of the ED and the cerebellum were measured, the SI ratio (SIR) was calculated, and ears with SIR ≥4 were identified. RESULTS: A high SIR was identified in the ED of 3.7% of ears affected by definite Meniere's disease (dMD), 100% of ears affected by large vestibular aqueduct syndrome (LVAS), and 7.1% of ears with no otological symptoms. On the whole, a significant relationship was found between the existence of vestibular or cochlear EH and the SIR in the ED. CONCLUSION: The MRI finding of high SI in the ED may indicate the mechanism of inner ear disturbances in ears with otological disorders, especially in those with LVAS, and it may suggest an underlying disorder in some ears in which otological symptoms are not apparent.

The periductal channels of the endolymphatic duct, hydrodynamic implications.

OBJECTIVE: To describe the anatomy of a small network of channels surrounding the human endolymphatic duct. STUDY DESIGN: Archival temporal bone sections and a surgical specimen were studied using a variety of techniques. SETTING: Temporal bone laboratory of the House Research Institute. SUBJECTS AND METHODS: Archival temporal bone sections were examined by light microscopy, 3D reconstruction, and immunohistochemical labeling. A surgical specimen was examined using electron microscopy. Sections from temporal bones with blocked endolymphatic ducts or amputated sacs were examined for the manifestations of endolymphatic hydrops. RESULTS: Peri-endolymphatic duct channels were found to extend from the proximal cisternal part of the endolymphatic sac to the supporting tissue of the saccule and utricle. Tissue in the channels, as seen by conventional and electron microscopy, is continuous with and identical with the tissue surrounding the endolymphatic duct. Tissue in the channels labels with the S100 antibody similar to the spiral ligament and supporting tissue of the vestibular end organs and suggests a neural crest origin, as did the presence of melanocytes. Obstruction of the endolymphatic duct resulted in endolymphatic hydrops whereas amputation of the sac did not. CONCLUSION: Endolymph is probably absorbed in the endolymphatic duct. The peri-endolymphatic duct channels that extend from the proximal sac to the supporting tissue of the saccule label with the S100 antibody and contain melanocytes suggest a neural crest origin and involvement in fluid and potassium hydrodynamics similar to those described for the similarly staining spiral ligament of the cochlea.

Morphology and function of Bast's valve: additional insight in its functioning using 3D-reconstruction.

The utriculo-endolymphatic valve was discovered by Bast in 1928. The function of Bast's valve is still unclear. By means of orthogonal-plane fluorescence optical sectioning (OPFOS) microscopy 3D-reconstructions of the valve and its surrounding region are depicted. The shape of the duct at the utricular side is that of a flattened funnel. In the direction of the endolymphatic duct and sac this funnel runs into a very narrow duct. The valve itself has a rigid 'arch-like' configuration. The opposing thin, one cell-layer thick, utricular membrane is highly compliant. We propose that opening and closure of the valve occurs through movement of the flexible base/utricular membrane away from and toward the relatively rigid valve lip.

Cochlear transducer operating point adaptation.

The operating point (OP) of outer hair cell (OHC) mechanotransduction can be defined as any shift away from the center position on the transduction function. It is a dc offset that can be described by percentage of the maximum transduction current or as an equivalent dc pressure in the ear canal. The change of OP can be determined from the changes of the second and third harmonics of the cochlear microphonic (CM) following a calibration of its initial value. We found that the initial OP was dependent on sound level and cochlear sensitivity. From CM generated by a lower sound level at 74 dB SPL to avoid saturation and suppression of basal turn cochlear amplification, the OHC OP was at constant 57% of the maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz best frequency location using a blunt probe. The force applied over the scala tympani induced an OP change as if the organ of Corti moved toward the scala vestibuli (SV) direction. During an application of the constant force, the second harmonic of the CM partially recovered toward the initial level, which could be described by two time constants. Removing the force induced recovery of the second harmonic to its normal level described by a single time constant. The force applied over the SV caused an opposite result. These data indicate an active mechanism for OHC transduction OP.

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear.

Bone morphogenetic proteins (BMPs) are expressed in the developing vertebrate inner ear and participate in inner ear axial patterning and the development of its sensory epithelium. BMP antagonists, such as noggin, chordin, gremlin, cerberus, and DAN (differential screening-selected gene aberrative in neuroblastoma) inhibit BMP activity and establish morphogenetic gradients during the patterning of many developing tissues and organs. In this study, the role of the BMP antagonist DAN in inner ear development was investigated. DAN-expressing cell pellets were implanted into the otocyst and the periotic mesenchyme to determine the effects of exogenous DAN on otic development. Similar to the effects on the inner ear seen after exposure of otocysts to the BMP4 antagonist noggin, semicircular canals were truncated or eliminated based upon the site of pellet implantation. Unique to the DAN implantations, however, were effects on the developing endolymphatic duct and sac. In DAN-treated inner ears, endolymphatic ducts and sacs were merged with the crus or grew into the superior semicircular canal. Both the canal and endolymphatic duct and sac effects were rescued by joint implantation of BMP4-expressing cells. Electroporation of DAN antisense morpholinos into the epithelium of stage 15-17 otocysts, blocking DAN protein synthesis, resulted in enlarged endolymphatic ducts and sacs as well as smaller semicircular canals in some cases. Taken together, these data suggest a role for DAN both in helping to regulate BMP activity spatially and temporally and in patterning and partitioning of the medial otic tissue between the endolymphatic duct/sac and medially derived inner ear structures.

Development of the endolymphatic sac and duct in the Japanese red-bellied newt, Cynops pyrrhogaster.

The development and maturation of the endolymphatic sac (ES) and duct (ED) were studied in the newt Cynops pyrrhogaster. The ES first appears as an oval capsule at the dorsal-medial tip of the otic vesicle at stage 39, about 11 days after oviposition. The ES consists of polymorphous epithelial cells with a minimum of cytoplasm. The intercellular space (IS) between the epithelial cells is narrow and has a smooth surface. At stage 44, the size of the ES increases as many vacuoles in the IS become filled. At stage 46, 18 days after oviposition, the ES elongates markedly and a slit-like lumen is found in the ES. The epithelium contains a few cell organelles which are scattered in the cytoplasm. The vacuoles in the IS are fused, which expands the IS. Two days later (stage 48), floccular material (endolymph) is present in the expanded lumen. The IS dilates and has a wide and irregular appearance. At stage 50, approximately 26 days after oviposition, the ES extends and expands significantly and crystals (otoconia) can now be seen in the widened lumen of the ES. The cytoplasm of the cuboidal epithelial cells contains an abundance of vesicles surrounded by ribosomes and Golgi complexes. Intercellular digitations are formed in the expanded IS. At stage 54, the ES forms a large bellow-like pouch. Numerous otoconia accumulate in the lumen. Free floating cells and cell debris can be seen in the lumen at this stage. The epithelial cells contain numerous cytoplasmic organelles which are evenly distributed in the cytoplasm. Granules are found in the apical and lateral cytoplasm. The IS is loose and displays a labyrinthine appearance. The primitive ED first appears as a connection between the ES and the saccule but no lumen is present inside at stage 39. At stage 46, a narrow lumen is formed in the ED, which corresponds to the formation of the ES lumen. At stage 50, as the ED extends, floccular material is seen in the lumen. At stage 54, the ED bears numerous microvilli on its luminal surface. Otoconia and endolymph are present in the ED. Tight junctions between the epithelial cells are formed at stage 46. A fully developed intercellular junctional complex is produced at stage 54. Based on the development of the ES and ED, the maturation of function of the ES and ED are discussed.

Erythrocyte removal and blood clearance in the endolymphatic sac. An experimental and TEM study.

The endolymphatic sac (ES) appears to serve as an immunologic/phagocytic defence organ. This may involve both specific and unspecific cell reactions for removal of both endogenous waste products and debris and foreign material. The present study was carried out in order to investigate whether the ES is involved in the removal of blood from the inner ear. The round window was exposed and the stapedial artery experimentally lesioned to cause bleeding. The ES was taken out after various time intervals and analyzed by TEM and LM, care being taken to maintain the structural integrity at all levels. This was done in order to see if the endolymphatic sac is involved in the removal of blood from the inner ear. The results indicate that the ES possesses hitherto unknown specific cellular properties for the disposal of blood and blood corpuscles. It is believed that this system may represent an important physiological function for regulation of homeostatic equilibrium around the inner ear sensory structures. The results also offer further support for the existence of a longitudinal "flow" of endolymph from the cochlea into the ES. Judging from the time it takes for erythrocytes to appear in the duct and sac, this flow would seem to take about 1-2 h in the mouse.

Fine structure of the endolymphatic duct in the rat. A scanning and transmission electron microscopy study.

To investigate the surface morphology of the endolymphatic duct epithelium, 8 rats were vascularly perfused with glutaraldehyde in a buffered and oxygenated blood substitute. Optimal preservation of the epithelium for scanning electron microscopy was attained by coating of the specimens with OsO4 and thiocarbohydrazide followed by a continuous dehydration procedure. Three types of cells were identified with the scanning electron microscope: A polygonal and oblong epithelial cell was observed in the largest number throughout the duct, whereas in the juxta-saccular half of the duct two additional types of epithelial cells were observed. The scanning electron microscopical observations are compared and discussed with reference to transmission electron microscopical observations of the endolymphatic duct.

Disturbance of regulation of sodium by cis-diamminedichloroplatinum in perilymph of the guinea pig cochlea.

We studied the acute effects of cis-diamminedichloroplatinum (CDDP) on the cochlear partition and inner ear fluid in the guinea pig. At 48 hours after the administration of a single intramuscular injection of CDDP, 12.5 mg/kg of body weight, the endocochlear resting potential (EP) was significantly decreased to 32.1 +/- 1.8 mV in the treated animals, versus 80.6 +/- 1.0 mV in the control animals. There was a significant rise in potassium (K+), sodium (Na+), and chlorine (Cl-) in the endolymph of the animals treated with CDDP as compared with the control animals. Only Na+ was found to increase significantly in the perilymph, reaching more than twice the level of the control animals; both K+ and Cl- remained within the normal range. Serum electrolytes also remained within the normal range. Evaluation of modified ionic permeabilities across the endolymph-perilymph barrier showed an apparent increase in Na+ permeability and a normal range of K+ and Cl- permeabilities. Histopathologic examination of the cochlea showed a moderate collapse of the endolymphatic space, with atrophy of the stria vascularis and destruction of the outer hair cells. The findings suggest that the acute changes produced in the cochlea by administration of CDDP were attributable to a breakdown in the regulation of Na+ metabolism in the perilymph.

Experimental interruption of the endolymphatic duct and its effect on the DC potential in the endolymphatic sac.

The endolymphatic sac (ES) of the guinea pig was isolated from the remainder of the inner ear by means of surgical interruption of the endolymphatic duct (ED). The DC potential in the ES lumen and the morphology of the ES were studied using glass micro-electrodes and a light microscope at various time intervals after the interruption of ED. The DC potential did not significantly change 1 h postoperatively, compared to findings in the non-operated ear, but a significant decrease of the DC potential was observed after 1, 3 and 7 days postoperatively. A histologically-stainable substance in the ES lumen was enhanced on the operated side. The isolated ES shows a disturbance of mechanism(s) maintaining the DC potential and there is a secretion of a stainable substance into its lumen.

Contribution of cell culture to the study of the physiology of the stria vascularis and Reissner's membrane.

Cell culture is a well-established tool in cell biology which may overcome the limitations of the experimental methods currently used to investigate the physiology of labyrinthine fluids. Using explant and dissociated cell culture technique, sheets of oriented cells derived from the stria vascularis and Reissner's membrane may be obtained, which allows new experimental approaches such as the patch-clamp technique. Other experimental approaches are considered which might improve our understanding of inner ear physiology.

Pressure transfer between the perilymph and the cerebrospinal fluid compartments in cats.

This is a review of our studies of the labyrinthine fluid pressure in cats subjected to pressure changes in the middle ear (implosive routes) and the cerebrospinal fluid compartment (explosive routes) as well as to changes in vascular and ambient pressures. The perilymph, cerebrospinal fluid (CSF), middle ear, venous and arterial pressures were measured with the cochlear aqueduct (CA) patent as well as surgically blocked. Experiments on explosive pressure changes revealed that the perilymph pressure was regulated by the CSF in case of CA patency. The CSF influence was dominant enough to obscure any direct effect on the labyrinth from other sources. With the CA obstructed the CSF influence on the labyrinth was apparently mainly via the endolymphatic sac and duct although limited and much delayed. Systemic arterial pressure changes had a pronounced influence on the perilymph pressure, but this effect was revealed only when the CSF influence was reduced by CA obstruction. Experiments on implosive and ambient pressure changes suggested that there was no fundamental difference in the perilymph response to equivalent levels of implosive versus hypobaric pressure. Three factors determined the effect of implosive and hypobaric pressure: the patency of the CA, the rate of the pressure change, and the eustachian tube function.

Haircell forward and reverse transduction: differential suppression and enhancement.

Cochlear outer haircells are believed to play a significant role in an amplification process which greatly enhances inner ear sensitivity. Haircell forward (mechanical-to-electrical) and reverse (electrical-to-mechanical) transduction may be involved. We have produced decreases in cochlear microphonic and increases in electrically-evoked cochlear emissions using the drug, furosemide. The data indicate forward and reverse transduction are not a simple bi-directional process and suggest that the outer haircells are part of a negative feedback system.

Cochlear blood flow in endolymphatic hydrops.

There is no animal model for Meniere's disease but by obliteration of the endolymphatic duct, endolymphatic hydrops may be achieved in several animal species. In order to measure the cochlear blood flow in ears with endolymphatic hydrops the endolymphatic duct was obliterated in 9 guinea pigs. The blood flow was measured with the microsphere method and the cochlear histology was studied. The regional and total blood flow was determined in the serially sectioned cochleas 2, 4 and 8 months after obliteration of the endolymphatic duct. No change in regional or total cochlear blood flow was observed in the hydropic ears.

Longitudinal flow of macromolecules in the endolymphatic space of the rat. An autoradiographical study.

Secretion and resorption of sulphated glycoproteins by the epithelial lining of the endolymphatic space of the rat were studied autoradiographically with the use of 35SO4 as a selective marker. This isotope was found to be incorporated into the sensory area of cristae and maculae and a small area of epithelial cells adjacent to the sensory epithelium. Thereafter 35S-labelled glycoproteins were secreted into cupulae and otolithic membranes. No such process could be established in the tectorial membrane. From the gradual disappearance of 35S-labelled glycoproteins from cupulae and otolithic membrane coupled with an accumulation of this substance in the lumen of the endolymphatic sac, the existence of a longitudinal flow under physiological conditions could be concluded. Resorption of glycoproteins by the saccus epithelium was found to be very slow. Accumulation of 35S-labelled glycoproteins in the endolymphatic duct after saccus obstruction indicates that, in addition to the endolymphatic sac, also the duct contributes to the mechanism underlying the longitudinal flow of macromolecules.

Human endolymphatic duct: possible mechanisms of endolymph outflow.

The ultrastructure of the normal human endolymphatic duct (ED) was observed by transmission electron microscopy. The role of the epithelium, the various regions of the subepithelial space, and vasculature in the resorption of endolymph was morphologically studied in order to generate testable hypotheses of human ED function. These hypothetical mechanisms of endolymph outflow at the level of the ED are a passive transcellular movement of water across the epithelium, driven by an osmotic gradient created by a subepithelial organic matrix; an active transcellular ion exchange with a passive transepithelial outflow of water, which stresses the importance of the dilated lateral intercellular spaces; and an active transcellular vacuolar endolymph outflow, whereby high molecular weight substances are removed by the ED. These mechanisms may be useful in designing experimental studies of the ED and in interpretation of retrospective light microscopic and transmission electron microscopic studies of patients with Meniere's disease.