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AJNR. American Journal of Neuroradiology May 2023The detection rate of premortem MR imaging endolymphatic hydrops is lower than that of postmortem endolymphatic hydrops in Ménière disease, indicating that current MR...
BACKGROUND AND PURPOSE
The detection rate of premortem MR imaging endolymphatic hydrops is lower than that of postmortem endolymphatic hydrops in Ménière disease, indicating that current MR imaging techniques may underestimate endolymphatic hydrops. Therefore, we prospectively investigated whether a novel high-resolution MR imaging technique, the 3D zoomed imaging technique with parallel transmission real inversion-recovery (3D-ZOOMit real IR), would improve the detection of endolymphatic hydrops compared with conventional 3D TSE inversion-recovery with real reconstruction.
MATERIALS AND METHODS
Fifty patients with definite unilateral Ménière disease were enrolled and underwent 3D-ZOOMit real IR and 3D TSE inversion-recovery with real reconstruction 6 hours after IV gadolinium injection. The endo- and perilymph spaces were scored separately. The contrast-to-noise ratio, SNR, and signal intensity ratio of the 2 sequences were respectively calculated and compared. The presence of endolymphatic hydrops was evaluated.
RESULTS
The endolymphatic space in the cochlea and vestibule was better visualized with 3D-ZOOMit real IR than with conventional 3D TSE inversion-recovery with real reconstruction (< .001). There were differences between the 2 sequences in the evaluation of no cochlear hydrops and cochlear hydrops (both, < .017). All contrast-to-noise ratio, SNR, and signal intensity ratio values of 3D-ZOOMit real IR images were statistically higher than those of conventional 3D TSE inversion-recovery with real reconstruction (all, < .001).
CONCLUSIONS
The 3D-ZOOMit real IR sequences are superior to conventional 3D TSE inversion-recovery with real reconstruction sequences in visualizing the endolymphatic space, detecting endolymphatic hydrops, and discovering contrast permeability.
Topics: Humans; Meniere Disease; Endolymphatic Hydrops; Magnetic Resonance Imaging; Imaging, Three-Dimensional; Vestibule, Labyrinth; Edema; Contrast Media
PubMed: 37105675
DOI: 10.3174/ajnr.A7842 -
Journal of Feline Medicine and Surgery Apr 2023Otitis media/interna (OMI) is the most common cause of peripheral vestibular disease in cats. The inner ear contains endolymph and perilymph, with perilymph being very...
OBJECTIVES
Otitis media/interna (OMI) is the most common cause of peripheral vestibular disease in cats. The inner ear contains endolymph and perilymph, with perilymph being very similar in composition to cerebrospinal fluid (CSF). As a very-low-protein fluid, it would be expected that normal perilymph should suppress on fluid-attenuated inversion recovery (FLAIR) MRI sequences. Based on this, we hypothesized that MRI FLAIR sequences should provide a non-invasive way of diagnosing inflammatory/infectious diseases such as OMI in cats, something that has previously been demonstrated in humans and, more recently, in dogs.
METHODS
This was a retrospective cohort study in which 41 cats met the inclusion criteria. They were placed into one of four groups, based on presenting complaint: clinical OMI (group A); inflammatory central nervous system (CNS) disease (group B); non-inflammatory structural disease (group C); and normal brain MRI (control group; group D). Transverse T2-weighted and FLAIR MRI sequences at the level of the inner ears bilaterally were compared in each group. The inner ear was selected as a region of interest using Horos, with a FLAIR suppression ratio calculated to account for variability in signal intensity between MRIs. This FLAIR suppression ratio was then compared between groups. Statistical analyses were performed by an experienced statistician, with a general linear model used to compare mean FLAIR suppression ratio, CSF nucleated cell count and CSF protein concentration between groups.
RESULTS
The OMI group (group A) had significantly lower FLAIR suppression scores compared with all other groups. The CSF cell count was also significantly increased in the OMI (group A) and inflammatory CNS disease (group B) groups compared with the control group (group D).
CONCLUSIONS AND RELEVANCE
This study demonstrates the utility of MRI FLAIR sequences in diagnosing presumptive OMI in cats, similarly to in humans and dogs. This study is relevant to practicing veterinary neurologists and radiologists in interpreting MRI findings in cats with suspected OMI.
Topics: Humans; Cats; Animals; Dogs; Retrospective Studies; Ear, Inner; Vestibular Diseases; Magnetic Resonance Imaging; Cat Diseases; Dog Diseases
PubMed: 37102785
DOI: 10.1177/1098612X231168001 -
Cureus Mar 2023This article highlights the importance of early identification and surgical treatment for extremely rare traumatic perilymphatic fistula (TPF) caused by an earpick,...
This article highlights the importance of early identification and surgical treatment for extremely rare traumatic perilymphatic fistula (TPF) caused by an earpick, which can pose the risk of irreversible hearing loss. Herein, we have described two cases of TPF and reviewed the literature primarily based on surgical treatment for penetrating ear trauma-induced TPF. We highlight the case of two females who sustained an accidental penetrating injury in the ear caused by the introduction of an earpick, leading to hearing loss and dizziness. Pure tone audiometry detected elevation of the bone-conduction thresholds. Computed tomography of Labyrinth revealed pneumolabyrinth in one case. Both patients underwent exploratory surgery, we completely repositioned the stapes that had invaginated into the vestibule in one case, in the other case, we reconnected the disarticulated incudostapedial joint and sealed perilymph fistula caused by rupture of the oval window. Both patients achieved hearing improvement and complete relief from the vestibular symptoms. The literature review indicated that a scar on the posterior aspect of the tympanic membrane was found in 44.4% of cases. Hearing improvement was observed in 45.5% and 25.0% of cases with invagination of stapes and fractured footplates by fistula repair, respectively. In terms of handling stapes dislocation, the hearing improvement rate was better in cases of complete stapes repositioning (66.7%) than those of complete or partial stapes removal (16.7%). Preoperative mild bone-conduction hearing loss or localized pneumolabyrinth are favorable factors for satisfactory hearing. When surgery is performed within 11 days of the injury, satisfactory hearing improvement can be expected.
PubMed: 37065325
DOI: 10.7759/cureus.36106 -
Otology & Neurotology : Official... Jun 2023Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full...
HYPOTHESIS
Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours.
BACKGROUND
We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing.
METHODS
Volumes of 1.0, 2.5, or 5.0 μL of artificial perilymph were injected into the cochlea at a rate of 1 μL/min. Compound action potential (CAP) and distortion product otoacoustic emission were performed to assess for hearing loss (HL), and confocal microscopy was used to evaluate the RWM for residual scarring or inflammation. To evaluate the distribution of agents within the cochlea after microneedle-mediated injection, 1.0 μL of FM 1-43 FX was injected into the cochlea, followed by whole mount cochlear dissection and confocal microscopy.
RESULTS
Direct intracochlear injection of 1.0 μL of artificial perilymph in vivo , corresponding to about 20% of the scala tympani volume, was safe and did not result in HL. However, injection of 2.5 or 5.0 μL of artificial perilymph into the cochlea produced statistically significant high-frequency HL persisting 48 hours postperforation. Assessment of RWMs 48 hours after perforation revealed no inflammatory changes or residual scarring. FM 1-43 FX injection resulted in distribution of the agent predominantly in the basal and middle turns.
CONCLUSION
Microneedle-mediated intracochlear delivery of small volumes relative to the volume of the scala tympani is feasible, safe, and does not cause HL in guinea pigs; however, injection of large volumes induces high-frequency HL. Injection of small volumes of a fluorescent agent across the RWM resulted in significant distribution within the basal turn, less distribution in the middle turn, and almost none in the apical turn. Microneedle-mediated intracochlear injection, along with our previously developed intracochlear aspiration, opens the pathway for precision inner ear medicine.
Topics: Guinea Pigs; Animals; Cicatrix; Cochlea; Scala Tympani; Pyridinium Compounds; Round Window, Ear; Perilymph
PubMed: 37026782
DOI: 10.1097/MAO.0000000000003845 -
Frontiers in Pharmacology 2023Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate...
Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic. The gap between rodents and humans may be bridged using larger animal models such as non-human primates. However, their use is challenging and impeded by administrative, regulatory, and financial hurdles. Other large animal models with more human-like inner ear dimensions are scarce. In this study, we analyzed the inner ears of piglets as a potential representative model for the human inner ear and established a surgical approach for intracochlear drug application and subsequent apical sampling. Further, controlled intracochlear delivery of fluorescein isothiocyanate-dextran (FITC-d) was carried out after the insertion of a novel, clinically applicable CE-marked cochlear catheter through the round window membrane. Two, six, and 24 hours after a single injection with this device, the intracochlear FITC-d distribution was determined in sequential perilymph samples. The fluorometrically assessed concentrations two hours after injection were compared to the FITC-d content in control groups, which either had been injected with a simple needle puncture through the round window membrane or the cochlear catheter in combination with a stapes vent hole. Our findings demonstrate not only significantly increased apical FITC-d concentrations when using the cochlear catheter but also higher total concentrations in all perilymph samples. Additionally, the concentration decreased after six and 24 hours and showed a more homogenous distribution compared to shorter observation times.
PubMed: 36969846
DOI: 10.3389/fphar.2023.1062379 -
Regenerative Biomaterials 2023Dexamethasone-loaded silicone matrices offer an interesting potential as innovative drug delivery systems, e.g. for the treatment of inner ear diseases or for...
Dexamethasone-loaded silicone matrices offer an interesting potential as innovative drug delivery systems, e.g. for the treatment of inner ear diseases or for pacemakers. Generally, very long drug release periods are targeted: several years/decades. This renders the development and optimization of novel drug products cumbersome: experimental feedback on the impact of the device design is obtained very slowly. A better understanding of the underlying mass transport mechanisms can help facilitating research in this field. A variety of silicone films were prepared in this study, loaded with amorphous or crystalline dexamethasone. Different polymorphic drug forms were investigated, the film thickness was altered and the drug optionally partially/completely exchanged by much more water-soluble dexamethasone 'phosphate'. Drug release studies in artificial perilymph, scanning electron microscopy, optical microscopy, differential scanning calorimetry, X-ray diffraction and Raman imaging were used to elucidate the physical states of the drugs and polymer, and of the systems' structure as well as dynamic changes thereof upon exposure to the release medium. Dexamethasone particles were initially homogeneously distributed throughout the systems. The hydrophobicity of the matrix former very much limits the amounts of water penetrating into the system, resulting in only partial drug dissolution. The mobile drug molecules diffuse out into the surrounding environment, due to concentration gradients. Interestingly, Raman imaging revealed that even very thin silicone layers (<20 µm) can effectively trap the drug for prolonged periods of time. The physical state of the drug (amorphous, crystalline) did not affect the resulting drug release kinetics to a noteworthy extent.
PubMed: 36911146
DOI: 10.1093/rb/rbad008 -
Pharmaceutics Jan 2023Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round...
Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker microbubbles (MBs; VisualSonics-Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 10 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.
PubMed: 36839763
DOI: 10.3390/pharmaceutics15020442 -
Frontiers in Pharmacology 2023Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral...
Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral steroid administration. In recent, intratympanic steroid injections such as dexamethasone have been used for the treatment of sudden hearing loss as well. It is injected into the tympanic cavity through its membrane and is expected to diffuse over the round window located between the tympanic cavity and the inner ear. However, in clinical situations, the delivery time of steroids to the inner ear is shorter than 24 h, which does not allow for a sufficient therapeutic effect. Therefore, we applied a previously invented dual viscosity mixture vehicle (DVV) for intratympanic dexamethasone to a guinea pig model, which could reduce the side effects of systemic steroid administration with sufficient dwelling time for the treatment of hearing loss, and we investigated the physiological changes with a global proteomic approach. In this study, we extracted perilymph in three different conditions from guinea pigs treated with dexamethasone-embedded DVV, dexamethasone mixed in saline, and control groups to compare proteomic changes using tandem mass spectrometry analysis. After liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis, we first identified 46 differentially expressed proteins (DEPs) that were statistically significant after one-way ANOVA multiple-sample test. We also performed pairwise comparisons among each group to identify DEPs closely related to the treatment response of dexamethasone-embedded DVV. Gene ontology enrichment analysis showed that these DEPs were mostly related to inflammation, immune, actin remodeling, and antioxidant-related processes. As a result, the proteome changes in the DVV-treated groups revealed that most upregulated proteins activate the cell proliferation process, and downregulated proteins inhibit apoptosis and inflammatory reactions. Moreover, the reactive oxygen process was also regulated by DEPs after DVV treatment.
PubMed: 36744248
DOI: 10.3389/fphar.2023.1081724 -
Frontiers in Neurology 2022Third window syndrome is a vestibular-cochlear disorder in humans in which a third mobile window of the otic capsule creates changes to the flow of sound pressure energy...
BACKGROUND
Third window syndrome is a vestibular-cochlear disorder in humans in which a third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The nature and location of this third mobile window can occur at many different sites (or multiple sites); however, the most common third mobile window is superior semicircular canal dehiscence (SSCD). There are two essential objective diagnostic characteristics needed to validate a model of SSCD: the creation of a pseudoconductive hearing loss and cVEMP increased amplitude and decreased threshold.
METHODS
Adult Mongolian gerbils ( = 36) received surgical fenestration of the superior semicircular canal of the left inner ear. ABR and c+VEMP testing were carried out prior to surgery and over acute (small 1 mm SSCD, 1-10 days) or prolonged (large 2 mm SSCD, 28 days) recovery. Because recovery of function occurred quickly, condenser brightfield stereomicroscopic examination of the dehiscence site was carried out for the small SSCD animals and compared to both ABRs and c+VEMPs. Micro-CT analysis was also completed with representative samples of control, day 3 and 10 post-SSCD animals.
RESULTS
The SSCD created a significant worsening of hearing thresholds of the left ear; especially in the lower frequency domain (1-4 kHz). Left (EXP)/right (CTL) ear comparisons ABR show significant worsening thresholds at the same frequency representations, which is a proxy for the human pseudoconductive hearing loss seen in SSCD. For the c+VEMP measurements, increased amplitude of the sound-induced response (N1 2.5 ms and P1 3.2 ms) was observed in animals that received larger fenestrations. As the bone regrew, the c+VEMP and ABR responses returned toward preoperative values. For small SSCD animals, micro-CT data show that progressive osteoneogenesis results in resurfacing of the SSCD without bony obliteration.
CONCLUSION
The large (2 mm) SSCD used in our gerbil model results in similar electrophysiologic findings observed in patients with SSCD. The changes observed also reverse and return to baseline as the SSCD heals by bone resurfacing (with the lumen intact). Hence, this model does not require a second surgical procedure to plug the SSCD.
PubMed: 36742050
DOI: 10.3389/fneur.2022.1035478