The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
Craig A Buchman - One of the best experts on this subject based on the ideXlab platform.
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Scala Tympani cochleostomy survey a follow up study
Laryngoscope, 2014Co-Authors: Claire E Iseli, Oliver F Adunka, Craig A BuchmanAbstract:Objectives/Hypothesis To reassess cochleostomy techniques among North American cochlear implant surgeons after a 6-year period of widespread education and research on the topic. Study Design Prospective cohort study. Methods A multiple-choice survey of cochlear implant techniques was distributed to surgeons attending the William House Cochlear Implant Study Group in 2006 and 2012. This survey contained questions regarding routine surgical access and cochleostomy techniques. Responses were anonymous, and >50% were repeat respondents. Statistical analysis sought changes in technique in the past 6 years. Results Comparisons between 2006 and 2012 responses revealed no significant changes in the proportion of surgeons identifying the facial nerve or chorda Tympani. By contrast, respondents in 2012 were more likely to drill off the round window niche overhang (P < .001), use a round window insertion (P < .001), or make a smaller cochleostomy (P = .003). In two images of a transfacial recess approach, there was a significant increase in the proportion choosing an inferior or anterior cochleostomy site over a superior location (image 1, 76% in 2006 to 92% in 2012, P = .003; image 3, 78% to 90%, respectively, P = .044). Conclusions This repeat survey documents a change in practice among cochlear implant surgeons. Specifically, Scala Tympani access techniques now appear to be more consistent with known anatomical relationships in the round window region. These findings may have resulted from the concerted education and research efforts over the past 6 years. Level of Evidence 4. Laryngoscope, 124:1928–1931, 2014
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cochleostomy versus round window insertions influence on functional outcomes in electric acoustic stimulation of the auditory system
Otology & Neurotology, 2014Co-Authors: Oliver F Adunka, Harold C Pillsbury, Margaret T Dillon, Marcia C Adunka, English R King, Craig A BuchmanAbstract:ObjectiveTo assess the potential influence of 2 different surgical access routes to Scala Tympani for hearing preservation cochlear implantation on outcomes.Study DesignRetrospective review.SettingTertiary care academic center.PatientsTwenty adult subjects participating in a prospective clinical tri
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Scala Tympani cochleostomy for cochlear implantation
Operative Techniques in Otolaryngology-head and Neck Surgery, 2010Co-Authors: Gregory J Basura, Oliver F Adunka, Craig A BuchmanAbstract:The use of cochlear implantation to treat sensorineural hearing loss continues to evolve as an increasing number of both adult and pediatric patients undergo this life-changing surgery. As our understanding of electrical stimulation of the auditory system unfolds, the importance of proper cochleostomy placement and intracochlear electrode positioning continues to evolve. Currently, atraumatic intracochlear electrode array implantation into Scala Tympani appears to optimize performance while providing the opportunity for hearing preservation for the purposes of bimodal stimulation. With these objectives in mind, this article describes the authors' surgical approach to gain access to Scala Tympani with the intent of minimizing trauma to the underlying structures. This approach is based on the results of multiple clinical and anatomical studies as well as on data from various temporal bone experiments. Based herein, the authors perform either direct round window insertions or create a round window-related cochleostomy either with or without a bony partition. Blind drilling procedures on the convexity of the promontory are avoided because this can result in either Scala vestibuli access or substantial intracochlear damage.
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Scala Tympani cochleostomy ii topography and histology
Laryngoscope, 2007Co-Authors: Oliver F Adunka, Andreas Radeloff, Wolfgang Gstoettner, Harold C Pillsbury, Craig A BuchmanAbstract:Objective: To assess intracochlear trauma using two different round window-related cochleostomy techniques in human temporal bones. Methods: Twenty-eight human temporal bones were included in this study. In 21 specimens, cochleostomies were initiated inferior to the round window (RW) annulus. In seven bones, cochleostomies were drilled anterior-inferior to the RW annulus. Limited cochlear implant electrode insertions were performed in 19 bones. In each specimen, promontory anatomy and cochleostomy drilling were photographically documented. Basal cochlear damage was assessed histologically and electrode insertion properties were documented in implanted bones. Results: All implanted specimens showed clear Scala Tympani electrode placements regardless of cochleostomy technique. All 21 inferior cochleostomies were atraumatic. Anterior-inferior cochleostomies resulted in various degrees of intracochlear trauma in all seven bones. Conclusion: For atraumatic opening of the Scala Tympani using a cochleostomy approach, initiation of drilling should proceed from inferior to the round window annulus, with gradual progression toward the undersurface of the lumen. While cochleostomies initiated anterior-inferior to the round window annulus resulted in Scala Tympani opening, many of these bones displayed varying degrees of intracochlear trauma that may result in hearing loss. When intracochlear drilling is avoided, the anterior bony margin of the cochleostomy remains a significant intracochlear impediment to in-line electrode insertion.
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Scala Tympani cochleostomy i results of a survey
Laryngoscope, 2007Co-Authors: Oliver F Adunka, Craig A BuchmanAbstract:Objective: To assess current surgical techniques for Scala Tympani cochlear implantation among North American surgeons. Material: A survey was distributed to all cochlear implant surgeons participating in the 2006 William House Cochlear Implant Study Group in Toronto, Canada. Participants were asked to anonymously identify their routine surgical practices. Images of trans-facial recess approaches to the round window and cochlear promontory were used in a multiple-choice fashion to assess the surgeon's typical exposure and cochleostomy location. Returned questionnaires were electronically processed and evaluated. Results: Fifty-five (75%) of 73 returned surveys had adequate data validity and availability. Landmark identification and preferred cochleostomy locations varied greatly. About 20% of surgeons selected cochleostomy locations superior to the round window membrane. Cochleostomy size and location appeared to be influenced by surgical experience and whether or not the round window overhang was drilled off. Conclusion: This survey clearly documents marked variations in surgical techniques for Scala Tympani cochlear implantation. Future studies should more clearly define the surgical anatomy of this region for appropriate placement of a Scala Tympani cochleostomy. These findings may ultimately have an impact on hearing and neural preservation cochlear implant surgeries.
Alec N Salt - One of the best experts on this subject based on the ideXlab platform.
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gentamicin concentration gradients in Scala Tympani perilymph following systemic applications
Audiology and Neuro-otology, 2013Co-Authors: Hartmut Hahn, Alec N Salt, Ulrike Schumacher, Stefan K PlontkeAbstract:It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of Scala Tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intraTympanic gentamicin applications for the treatment of Meniere's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns.
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dexamethasone levels and base to apex concentration gradients in the Scala Tympani perilymph after intracochlear delivery in the guinea pig
Otology & Neurotology, 2012Co-Authors: Hartmut Hahn, Alec N Salt, Thorsten Biegner, Bernd Kammerer, Ursular Delabar, Jared J Hartsock, Stefan K PlontkeAbstract:Hypothesis To determine whether intracochlearly applied dexamethasone will lead to better control of drug levels, higher peak concentrations and lower base-to apex concentration gradients in Scala Tympani (ST) of the guinea pig than after intraTympanic (round window, RW) application.
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dexamethasone concentration gradients along Scala Tympani after application to the round window membrane
Otology & Neurotology, 2008Co-Authors: Stefan K Plontke, Thorsten Biegner, Bernd Kammerer, Ursular Delabar, Alec N SaltAbstract:Hypothesis:Local application of dexamethasone-21-dihydrogen-phosphate (Dex-P) to the round window (RW) membrane of guinea pigs produces a substantial basal-apical concentration gradient in Scala Tympani (ST) perilymph.Background:In recent years, intraTympanically applied glucocorticoids are increasi
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concentration gradient along the Scala Tympani after local application of gentamicin to the round window membrane
Laryngoscope, 2007Co-Authors: Stefan K Plontke, Robert Mynatt, Ruth M Gill, Stefan Borgmann, Alec N SaltAbstract:Objectives: The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. Methods: A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the Scala Tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. Results: Substantial gradients of gentamicin along the length of the Scala Tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. Conclusions: The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients.
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Demonstration of a Longitudinal Concentration Gradient Along Scala Tympani by Sequential Sampling of Perilymph from the Cochlear Apex
Journal of the Association for Research in Otolaryngology, 2006Co-Authors: Robert Mynatt, Stefan K Plontke, Ruth M Gill, Shane A. Hale, Alec N SaltAbstract:Local applications of drugs to the inner ear are increasingly being used to treat patients' inner ear disorders. Knowledge of the pharmacokinetics of drugs in the inner ear fluids is essential for a scientific basis for such treatments. When auditory function is of primary interest, the drug's kinetics in Scala Tympani (ST) must be established. Measurement of drug levels in ST is technically difficult because of the known contamination of perilymph samples taken from the basal cochlear turn with cerebrospinal fluid (CSF). Recently, we reported a technique in which perilymph was sampled from the cochlear apex to minimize the influence of CSF contamination ( J. Neurosci. Methods , doi: 10.1016/j.jneumeth.2005.10.008 ). This technique has now been extended by taking smaller fluid samples sequentially from the cochlear apex, which can be used to quantify drug gradients along ST. The sampling and analysis methods were evaluated using an ionic marker, trimethylphenylammonium (TMPA), that was applied to the round window membrane. After loading perilymph with TMPA, 10 1-μL samples were taken from the cochlear apex. The TMPA content of the samples was consistent with the first sample containing perilymph from apical regions and the fourth or fifth sample containing perilymph from the basal turn. TMPA concentration decreased in subsequent samples, as they increasingly contained CSF that had passed through ST. Sample concentration curves were interpreted quantitatively by simulation of the experiment with a finite element model and by an automated curve-fitting method by which the apical–basal gradient was estimated. The study demonstrates that sequential apical sampling provides drug gradient data for ST perilymph while avoiding the major distortions of sample composition associated with basal turn sampling. The method can be used for any substance for which a sensitive assay is available and is therefore of high relevance for the development of preclinical and clinical strategies for local drug delivery to the inner ear.
Oliver F Adunka - One of the best experts on this subject based on the ideXlab platform.
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Scala Tympani cochleostomy survey a follow up study
Laryngoscope, 2014Co-Authors: Claire E Iseli, Oliver F Adunka, Craig A BuchmanAbstract:Objectives/Hypothesis To reassess cochleostomy techniques among North American cochlear implant surgeons after a 6-year period of widespread education and research on the topic. Study Design Prospective cohort study. Methods A multiple-choice survey of cochlear implant techniques was distributed to surgeons attending the William House Cochlear Implant Study Group in 2006 and 2012. This survey contained questions regarding routine surgical access and cochleostomy techniques. Responses were anonymous, and >50% were repeat respondents. Statistical analysis sought changes in technique in the past 6 years. Results Comparisons between 2006 and 2012 responses revealed no significant changes in the proportion of surgeons identifying the facial nerve or chorda Tympani. By contrast, respondents in 2012 were more likely to drill off the round window niche overhang (P < .001), use a round window insertion (P < .001), or make a smaller cochleostomy (P = .003). In two images of a transfacial recess approach, there was a significant increase in the proportion choosing an inferior or anterior cochleostomy site over a superior location (image 1, 76% in 2006 to 92% in 2012, P = .003; image 3, 78% to 90%, respectively, P = .044). Conclusions This repeat survey documents a change in practice among cochlear implant surgeons. Specifically, Scala Tympani access techniques now appear to be more consistent with known anatomical relationships in the round window region. These findings may have resulted from the concerted education and research efforts over the past 6 years. Level of Evidence 4. Laryngoscope, 124:1928–1931, 2014
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cochleostomy versus round window insertions influence on functional outcomes in electric acoustic stimulation of the auditory system
Otology & Neurotology, 2014Co-Authors: Oliver F Adunka, Harold C Pillsbury, Margaret T Dillon, Marcia C Adunka, English R King, Craig A BuchmanAbstract:ObjectiveTo assess the potential influence of 2 different surgical access routes to Scala Tympani for hearing preservation cochlear implantation on outcomes.Study DesignRetrospective review.SettingTertiary care academic center.PatientsTwenty adult subjects participating in a prospective clinical tri
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Scala Tympani cochleostomy for cochlear implantation
Operative Techniques in Otolaryngology-head and Neck Surgery, 2010Co-Authors: Gregory J Basura, Oliver F Adunka, Craig A BuchmanAbstract:The use of cochlear implantation to treat sensorineural hearing loss continues to evolve as an increasing number of both adult and pediatric patients undergo this life-changing surgery. As our understanding of electrical stimulation of the auditory system unfolds, the importance of proper cochleostomy placement and intracochlear electrode positioning continues to evolve. Currently, atraumatic intracochlear electrode array implantation into Scala Tympani appears to optimize performance while providing the opportunity for hearing preservation for the purposes of bimodal stimulation. With these objectives in mind, this article describes the authors' surgical approach to gain access to Scala Tympani with the intent of minimizing trauma to the underlying structures. This approach is based on the results of multiple clinical and anatomical studies as well as on data from various temporal bone experiments. Based herein, the authors perform either direct round window insertions or create a round window-related cochleostomy either with or without a bony partition. Blind drilling procedures on the convexity of the promontory are avoided because this can result in either Scala vestibuli access or substantial intracochlear damage.
-
Scala Tympani cochleostomy ii topography and histology
Laryngoscope, 2007Co-Authors: Oliver F Adunka, Andreas Radeloff, Wolfgang Gstoettner, Harold C Pillsbury, Craig A BuchmanAbstract:Objective: To assess intracochlear trauma using two different round window-related cochleostomy techniques in human temporal bones. Methods: Twenty-eight human temporal bones were included in this study. In 21 specimens, cochleostomies were initiated inferior to the round window (RW) annulus. In seven bones, cochleostomies were drilled anterior-inferior to the RW annulus. Limited cochlear implant electrode insertions were performed in 19 bones. In each specimen, promontory anatomy and cochleostomy drilling were photographically documented. Basal cochlear damage was assessed histologically and electrode insertion properties were documented in implanted bones. Results: All implanted specimens showed clear Scala Tympani electrode placements regardless of cochleostomy technique. All 21 inferior cochleostomies were atraumatic. Anterior-inferior cochleostomies resulted in various degrees of intracochlear trauma in all seven bones. Conclusion: For atraumatic opening of the Scala Tympani using a cochleostomy approach, initiation of drilling should proceed from inferior to the round window annulus, with gradual progression toward the undersurface of the lumen. While cochleostomies initiated anterior-inferior to the round window annulus resulted in Scala Tympani opening, many of these bones displayed varying degrees of intracochlear trauma that may result in hearing loss. When intracochlear drilling is avoided, the anterior bony margin of the cochleostomy remains a significant intracochlear impediment to in-line electrode insertion.
-
Scala Tympani cochleostomy i results of a survey
Laryngoscope, 2007Co-Authors: Oliver F Adunka, Craig A BuchmanAbstract:Objective: To assess current surgical techniques for Scala Tympani cochlear implantation among North American surgeons. Material: A survey was distributed to all cochlear implant surgeons participating in the 2006 William House Cochlear Implant Study Group in Toronto, Canada. Participants were asked to anonymously identify their routine surgical practices. Images of trans-facial recess approaches to the round window and cochlear promontory were used in a multiple-choice fashion to assess the surgeon's typical exposure and cochleostomy location. Returned questionnaires were electronically processed and evaluated. Results: Fifty-five (75%) of 73 returned surveys had adequate data validity and availability. Landmark identification and preferred cochleostomy locations varied greatly. About 20% of surgeons selected cochleostomy locations superior to the round window membrane. Cochleostomy size and location appeared to be influenced by surgical experience and whether or not the round window overhang was drilled off. Conclusion: This survey clearly documents marked variations in surgical techniques for Scala Tympani cochlear implantation. Future studies should more clearly define the surgical anatomy of this region for appropriate placement of a Scala Tympani cochleostomy. These findings may ultimately have an impact on hearing and neural preservation cochlear implant surgeries.
Yehoash Raphael - One of the best experts on this subject based on the ideXlab platform.
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visualization of spiral ganglion neurites within the Scala Tympani with a cochlear implant in situ
Journal of Neuroscience Methods, 2009Co-Authors: Jennifer A Chikar, Bryan E. Pfingst, Shelley A Batts, Yehoash RaphaelAbstract:Current cochlear histology methods do not allow in situ processing of cochlear implants. The metal components of the implant preclude standard embedding and mid-modiolar sectioning, and whole mounts do not have the spatial resolution needed to view the implant within the Scala Tympani. One focus of recent auditory research is the regeneration of structures within the cochlea, particularly the ganglion cells and their processes, and there are multiple potential benefits to cochlear implant users from this work. To facilitate experimental investigations of auditory nerve regeneration performed in conjunction with cochlear implantation, it is critical to visualize the cochlear tissue and the implant together to determine if the nerve has made contact with the implant. This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament-labeled nerve processes within the Scala Tympani, and the spatial relationship between them.
Stefan K Plontke - One of the best experts on this subject based on the ideXlab platform.
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gentamicin concentration gradients in Scala Tympani perilymph following systemic applications
Audiology and Neuro-otology, 2013Co-Authors: Hartmut Hahn, Alec N Salt, Ulrike Schumacher, Stefan K PlontkeAbstract:It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of Scala Tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intraTympanic gentamicin applications for the treatment of Meniere's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns.
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dexamethasone levels and base to apex concentration gradients in the Scala Tympani perilymph after intracochlear delivery in the guinea pig
Otology & Neurotology, 2012Co-Authors: Hartmut Hahn, Alec N Salt, Thorsten Biegner, Bernd Kammerer, Ursular Delabar, Jared J Hartsock, Stefan K PlontkeAbstract:Hypothesis To determine whether intracochlearly applied dexamethasone will lead to better control of drug levels, higher peak concentrations and lower base-to apex concentration gradients in Scala Tympani (ST) of the guinea pig than after intraTympanic (round window, RW) application.
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dexamethasone concentration gradients along Scala Tympani after application to the round window membrane
Otology & Neurotology, 2008Co-Authors: Stefan K Plontke, Thorsten Biegner, Bernd Kammerer, Ursular Delabar, Alec N SaltAbstract:Hypothesis:Local application of dexamethasone-21-dihydrogen-phosphate (Dex-P) to the round window (RW) membrane of guinea pigs produces a substantial basal-apical concentration gradient in Scala Tympani (ST) perilymph.Background:In recent years, intraTympanically applied glucocorticoids are increasi
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concentration gradient along the Scala Tympani after local application of gentamicin to the round window membrane
Laryngoscope, 2007Co-Authors: Stefan K Plontke, Robert Mynatt, Ruth M Gill, Stefan Borgmann, Alec N SaltAbstract:Objectives: The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. Methods: A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the Scala Tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. Results: Substantial gradients of gentamicin along the length of the Scala Tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. Conclusions: The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients.
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Demonstration of a Longitudinal Concentration Gradient Along Scala Tympani by Sequential Sampling of Perilymph from the Cochlear Apex
Journal of the Association for Research in Otolaryngology, 2006Co-Authors: Robert Mynatt, Stefan K Plontke, Ruth M Gill, Shane A. Hale, Alec N SaltAbstract:Local applications of drugs to the inner ear are increasingly being used to treat patients' inner ear disorders. Knowledge of the pharmacokinetics of drugs in the inner ear fluids is essential for a scientific basis for such treatments. When auditory function is of primary interest, the drug's kinetics in Scala Tympani (ST) must be established. Measurement of drug levels in ST is technically difficult because of the known contamination of perilymph samples taken from the basal cochlear turn with cerebrospinal fluid (CSF). Recently, we reported a technique in which perilymph was sampled from the cochlear apex to minimize the influence of CSF contamination ( J. Neurosci. Methods , doi: 10.1016/j.jneumeth.2005.10.008 ). This technique has now been extended by taking smaller fluid samples sequentially from the cochlear apex, which can be used to quantify drug gradients along ST. The sampling and analysis methods were evaluated using an ionic marker, trimethylphenylammonium (TMPA), that was applied to the round window membrane. After loading perilymph with TMPA, 10 1-μL samples were taken from the cochlear apex. The TMPA content of the samples was consistent with the first sample containing perilymph from apical regions and the fourth or fifth sample containing perilymph from the basal turn. TMPA concentration decreased in subsequent samples, as they increasingly contained CSF that had passed through ST. Sample concentration curves were interpreted quantitatively by simulation of the experiment with a finite element model and by an automated curve-fitting method by which the apical–basal gradient was estimated. The study demonstrates that sequential apical sampling provides drug gradient data for ST perilymph while avoiding the major distortions of sample composition associated with basal turn sampling. The method can be used for any substance for which a sensitive assay is available and is therefore of high relevance for the development of preclinical and clinical strategies for local drug delivery to the inner ear.
