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1.
Clin Ophthalmol ; 17: 3601-3611, 2023.
Article in English | MEDLINE | ID: mdl-38026599

ABSTRACT

Objective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF. Methods: The overall study population comprised eyes that were given ≥1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥3 brolucizumab injections over ≥12 or ≥18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥2 brolucizumab injections and ≥1 other anti-VEGF over ≥12 or ≥18 months. Results: A total of 482 eyes received ≥1 brolucizumab injection during the study period. Mean VA changes from baseline were -1.1±15.1 letters (BRO cohort; n = 174) and 1.3±13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0±13.5 letters (BRO cohort; n = 95) and -7.3±17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9±48.1 days (BRO cohort) and +11.1±17.3 days (ALT cohort) at Month 12 and +36.3±52.3 days (BRO cohort) and +14.0±19.9 days (ALT cohort) at Month 18. Mean changes in CMT were -35.2±108.1 µm (BRO cohort) and -31.5±91.2 µm (ALT cohort) at Month 12 and -38.9±75.0 µm (BRO cohort) and -9.0±59.9 µm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes. Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.

2.
J Assoc Res Otolaryngol ; 24(3): 325-337, 2023 06.
Article in English | MEDLINE | ID: mdl-37253962

ABSTRACT

Otitis media (OM), a common ear infection, is characterized by the presence of an accumulated middle ear effusion (MEE) in a normally air-filled middle ear cavity. While assessing the MEE plays a critical role in the overall management of OM, identifying and examining the MEE is challenging with the current diagnostic tools since the MEE is located behind the semi-opaque eardrum. The objective of this cross-sectional, observational study is to non-invasively visualize and characterize MEEs and bacterial biofilms in the middle ear. A portable, handheld, otoscope-integrated optical coherence tomography (OCT) system combined with novel analytical methods has been developed. In vivo middle ear OCT images were acquired from 53 pediatric subjects (average age of 3.9 years; all awake during OCT imaging) diagnosed with OM and undergoing a surgical procedure (ear tube surgery) to aspirate the MEE and aerate the middle ear. In vivo middle ear OCT acquired prior to the surgery was compared with OCT of the freshly extracted MEEs, clinical diagnosis, and post-operative evaluations. Among the subjects who were identified with the presence of MEEs, 89.6% showed the presence of the TM-adherent biofilm in in vivo OCT. This study provides an atlas of middle ear OCT images exhibiting a range of depth-resolved MEE features, which can only be visualized and assessed non-invasively through OCT. Quantitative metrics of OCT images acquired prior to the surgery were statistically correlated with surgical evaluations of MEEs. Measurements of MEE characteristics will provide new readily available information that can lead to improved diagnosis and management strategies for the highly prevalent OM in children.


Subject(s)
Otitis Media with Effusion , Otitis Media , Child , Humans , Child, Preschool , Otitis Media with Effusion/diagnosis , Cross-Sectional Studies , Otitis Media/diagnostic imaging , Otitis Media/microbiology , Ear, Middle/diagnostic imaging , Biofilms
3.
Int J Retina Vitreous ; 9(1): 8, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36726178

ABSTRACT

BACKGROUND: The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months. METHODS: This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving ≥ 1 brolucizumab injection, the second receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 12 months and the third cohort receiving ≥ 3 brolucizumab injections with a follow-up period of ≥ 18 months. Study endpoints included changes from baseline at 12 or 18 months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers. RESULTS: Overall, 482 eyes received ≥ 1 brolucizumab injection; 174 eyes received ≥ 3 brolucizumab injections with ≥ 12 months of follow-up, and 95 eyes received ≥ 3 brolucizumab injections with ≥ 18 months of follow-up. VA (mean [95% confidence intervals]) remained stable relative to baseline after 12 months (- 1.1 [- 3.7, 1.6] letters; p = 0.42) and 18 months (0.0 [- 3.1, 3.1] letters; p = 0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p < 0.0001), and eyes with pre-switch injection intervals < 8 weeks were able to have their injection intervals extended by 23.6 days longer than eyes with pre-switch injection intervals ≥ 8 weeks. At 18 months, injection intervals were extended by 36.3 (25.6, 46.9) days (p < 0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18 months (12 months: - 35.2 (- 51.7, - 18.8) µm, p < 0.0001; 18 months: - 38.9 (- 54.3, - 22.0) µm, p < 0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes. CONCLUSIONS: This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs.

4.
Biomed Opt Express ; 13(6): 3601-3614, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35781950

ABSTRACT

Otitis media (OM) is an extremely common disease that affects children worldwide. Optical coherence tomography (OCT) has emerged as a noninvasive diagnostic tool for OM, which can detect the presence and quantify the properties of middle ear fluid and biofilms. Here, the use of OCT data from the chinchilla, the gold-standard OM model for the human disease, is used to supplement a human image database to produce diagnostically relevant conclusions in a machine learning model. Statistical analysis shows the datatypes are compatible, with a blended-species model reaching ∼95% accuracy and F1 score, maintaining performance while additional human data is collected.

5.
Sci Rep ; 11(1): 5176, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33664323

ABSTRACT

Studying the impact of antibiotic treatment on otitis media (OM), the leading cause of primary care office visits during childhood, is critical to develop appropriate treatment strategies. Tracking dynamic middle ear conditions during antibiotic treatment is not readily applicable in patients, due to the limited diagnostic techniques available to detect the smaller amount and variation of middle ear effusion (MEE) and middle ear bacterial biofilm, responsible for chronic and recurrent OM. To overcome these challenges, a handheld optical coherence tomography (OCT) system has been developed to monitor in vivo response of biofilms and MEEs in the OM-induced chinchilla model, the standard model for human OM. As a result, the formation of MEE as well as biofilm adherent to the tympanic membrane (TM) was longitudinally assessed as OM developed. Various types of MEEs and biofilms in the chinchilla model were identified, which showed comparable features as those in humans. Furthermore, the effect of antibiotics on the biofilm as well as the amount and type of MEEs was investigated with low-dose and high-dose treatment (ceftriaxone). The capability of OCT to non-invasively track and examine middle ear conditions is highly beneficial for therapeutic OM studies and will lead to improved management of OM in patients.


Subject(s)
Biofilms/drug effects , Ear, Middle/diagnostic imaging , Otitis Media with Effusion/drug therapy , Otitis Media/drug therapy , Animals , Anti-Bacterial Agents/pharmacology , Ceftriaxone/pharmacology , Chinchilla/microbiology , Disease Models, Animal , Ear, Middle/drug effects , Ear, Middle/microbiology , Ear, Middle/pathology , Humans , Otitis Media/diagnostic imaging , Otitis Media/microbiology , Otitis Media/pathology , Otitis Media with Effusion/diagnostic imaging , Otitis Media with Effusion/microbiology , Otitis Media with Effusion/pathology , Tomography, Optical Coherence , Tympanic Membrane/drug effects , Tympanic Membrane/microbiology , Tympanic Membrane/pathology
6.
J Biophotonics ; 14(4): e202000215, 2021 04.
Article in English | MEDLINE | ID: mdl-33439538

ABSTRACT

Decreased mobility of the human eardrum, the tympanic membrane (TM), is an essential indicator of a prevalent middle ear infection. The current diagnostic method to assess TM mobility is via pneumatic otoscopy, which provides subjective and qualitative information of subtle motion. In this study, a handheld spectral-domain pneumatic optical coherence tomography system was developed to simultaneously measure the displacement of the TM, air pressure inputs applied to a sealed ear canal, and to perform digital pneumatic otoscopy. A novel approach based on quantitative parameters is presented to characterize spatial and temporal variations of the dynamic TM motion. Furthermore, the TM motions of normal middle ears are compared with those of ears with middle ear infections. The capability of noninvasively measuring the rapid motion of the TM is beneficial to understand the complex dynamics of the human TM, and can ultimately lead to improved diagnosis and management of middle ear infections.


Subject(s)
Otitis Media , Tympanic Membrane , Ear, Middle/diagnostic imaging , Humans , Motion , Tomography, Optical Coherence , Tympanic Membrane/diagnostic imaging
7.
Ear Hear ; 41(4): 811-824, 2020.
Article in English | MEDLINE | ID: mdl-31634213

ABSTRACT

OBJECTIVES: Wideband acoustic immittance (WAI) noninvasively assesses middle ear function by measuring the sound conduction over a range of audible frequencies. Although several studies have shown the potential of WAI for detecting the presence of middle ear effusions (MEEs), determining the effects of MEE type and amount on WAI in vivo has been challenging due to the anatomical location of middle ear cavity. The purpose of this study is to correlate WAI measurements with physical characteristics of the middle ear and MEEs determined by optical coherence tomography (OCT), a noninvasive optical imaging technique. DESIGN: Sixteen pediatric subjects (average age of 7 ± 4 years) were recruited from the primary care clinic at Carle Foundation Hospital (Urbana, IL). A total of 22 ears (normal: 15 ears, otitis media with effusion: 6 ears, and acute otitis media: 1 ear, based on physician's diagnosis) were examined via standard otoscopy, tympanometry, OCT imaging, and WAI measurements in a busy, community-based clinical setting. Cross-sectional OCT images were analyzed to quantitatively assess the presence, type (relative turbidity based on the amount of scattering), and amount (relative fluid level) of MEEs. These OCT metrics were utilized to categorize subject ears into no MEE (control), biofilm without a MEE, serous-scant, serous-severe, mucoid-scant, and mucoid-severe MEE groups. The absorbance levels in each group were statistically evaluated at α = 0.05. RESULTS: The absorbance of the control group showed a similar trend when compared with a pediatric normative dataset, and the presence of an MEE generally decreased the power absorbance. The mucoid MEE group showed significantly less power absorbance from 2.74 to 4.73 kHz (p < 0.05) when compared with the serous MEE group, possibly due to the greater mass impeding the middle ear system. Similarly, the greater amount of middle ear fluid contributed to the lower power absorbance from 1.92 to 2.37 kHz (p< 0.05), when compared with smaller amounts of fluid. As expected, the MEEs with scant fluid only significantly affected the power absorbance at frequencies greater than 4.85 kHz. A large variance in the power absorbance was observed between 2 and 5 kHz, suggesting the dependence on both the type and amount of MEE. CONCLUSIONS: Physical characteristics of the middle ear and MEEs quantified from noninvasive OCT images can be helpful to understand abnormal WAI measurements. Mucoid MEEs decrease the power absorbance more than serous MEEs, and the greater amounts of MEE decreases the power absorbance, especially at higher (>2 kHz) frequencies. As both the type and amount of MEE can significantly affect WAI measurements, further investigations to correlate acoustic measurements with physical characteristics of middle ear conditions in vivo is needed.


Subject(s)
Otitis Media with Effusion , Acoustic Impedance Tests , Acoustics , Child , Child, Preschool , Cross-Sectional Studies , Ear, Middle/diagnostic imaging , Female , Humans , Male , Otitis Media with Effusion/diagnostic imaging , Tomography, Optical Coherence
8.
NPJ Digit Med ; 2: 22, 2019.
Article in English | MEDLINE | ID: mdl-31304369

ABSTRACT

The diagnosis and treatment of otitis media (OM), a common childhood infection, is a significant burden on the healthcare system. Diagnosis relies on observer experience via otoscopy, although for non-specialists or inexperienced users, accurate diagnosis can be difficult. In past studies, optical coherence tomography (OCT) has been used to quantitatively characterize disease states of OM, although with the involvement of experts to interpret and correlate image-based indicators of infection with clinical information. In this paper, a flexible and comprehensive framework is presented that automatically extracts features from OCT images, classifies data, and presents clinically relevant results in a user-friendly platform suitable for point-of-care and primary care settings. This framework was used to test the discrimination between OCT images of normal controls, ears with biofilms, and ears with biofilms and middle ear fluid (effusion). Predicted future performance of this classification platform returned promising results (90%+ accuracy) in various initial tests. With integration into patient healthcare workflow, users of all levels of medical experience may be able to collect OCT data and accurately identify the presence of middle ear fluid and/or biofilms.

9.
Sci Rep ; 8(1): 8777, 2018 06 08.
Article in English | MEDLINE | ID: mdl-29884809

ABSTRACT

Otitis media (OM) is a common ear infection and a leading cause of conductive hearing loss in the pediatric population. Current technologies such as otoscopy, pneumatic otoscopy, tympanometry, and acoustic reflectometry are used to diagnose OM, which can reasonably diagnose the infection with a sensitivity and specificity of 50-90% and 60-90%, respectively. However, these techniques provide limited information about the physical architecture of the tympanic membrane (TM), or what may lie behind it. Here, we report the detection of nanometer-scale structural changes of the TM using nano-sensitive optical coherence tomography (nsOCT). In total, an image dataset from 65 pediatric subjects from three different groups (normal, acute OM, and chronic OM) and with longitudinal image-based analysis of ear infections were included in this study. The nsOCT data were correlated with physician diagnosis and with OCT thickness measurements and were found to be in good agreement with these results. We report that nsOCT detects in vivo structural deformations of the TM earlier than OCT alone, and enhances the detection sensitivity of OCT measurements. This unique technique for early detection of nano-scale structural modifications in the TM has the potential to aid in our understanding of microbiological effects, and possibly for early diagnosis and more effective treatment of OM.


Subject(s)
Otitis Media/diagnostic imaging , Tomography, Optical Coherence/methods , Tympanic Membrane/diagnostic imaging , Algorithms , Child , Equipment Design , Humans , Otitis Media/pathology , Otitis Media/surgery , Otoscopy/methods , Tomography, Optical Coherence/instrumentation , Tympanic Membrane/pathology , Tympanic Membrane/surgery
10.
Biomed Opt Express ; 9(2): 397-409, 2018 Feb 01.
Article in English | MEDLINE | ID: mdl-29552381

ABSTRACT

Pneumatic otoscopy to assess the mobility of the tympanic membrane (TM) is a highly recommended diagnostic method of otitis media (OM), a widespread middle ear infection characterized by the fluid accumulation in the middle ear. Nonetheless, limited depth perception and subjective interpretation of small TM displacements have challenged the appropriate and efficient examination of TM dynamics experienced during OM. In this paper, a pneumatic otoscope integrated with low coherence interferometry (LCI) was adapted with a controlled pressure-generating system to record the pneumatic response of the TM and to estimate middle ear pressure (MEP). Forty-two ears diagnosed as normal (n = 25), with OM (n = 10), or associated with an upper respiratory infection (URI) (n = 7) were imaged with a pneumatic LCI otoscope with an axial, transverse, and temporal resolution of 6 µm, 20 µm, and 1 msec, respectively. The TM displacement under pneumatic pressure transients (a duration of 0.5 sec with an intensity of ± 150 daPa) was measured to compute two metrics (compliance and amplitude ratio). These metrics were correlated with peak acoustic admittance and MEP from tympanometry and statistically compared via Welch's t-test. As a result, the compliance represents pneumatic TM mobility, and the amplitude ratio estimates MEP. The presence of a middle ear effusion (MEE) significantly decreased compliance (p<0.001). The amplitude ratio of the OM group was statistically less than that of the normal group (p<0.01), indicating positive MEP. Unlike tympanometry, pneumatic LCI otoscopy quantifies TM mobility as well as MEP regardless of MEE presence. With combined benefits of pneumatic otoscopy and tympanometry, pneumatic LCI otoscopy may provide new quantitative metrics for understanding TM dynamics and diagnosing OM.

11.
Otolaryngol Head Neck Surg ; 159(1): 117-126, 2018 07.
Article in English | MEDLINE | ID: mdl-29587128

ABSTRACT

Objective To characterize otitis media-associated structures affixed to the mucosal surface of the tympanic membrane (TM) in vivo and in surgically recovered in vitro samples. Study Design Prospective case series without comparison. Setting Outpatient surgical care center. Subjects and Methods Forty pediatric subjects scheduled for tympanostomy tube placement surgery were imaged intraoperatively under general anesthesia. Postmyringotomy, a portable optical coherence tomography (OCT) imaging system assessed for the presence of any biofilm affixed to the mucosal surface of the TM. Samples of suspected microbial infection-related structures were collected through the myringotomy incision. The sampled site was subsequently reimaged with OCT to confirm collection from the original image site on the TM. In vitro analysis based on confocal laser scanning microscope (CLSM) images of fluorescence in situ hybridization-tagged samples and polymerase chain reaction (PCR) provided microbiological characterization and verification of biofilm activity. Results OCT imaging was achieved for 38 of 40 subjects (95%). Images from 38 of 38 (100%) of subjects observed with OCT showed the presence of additional microbial infection-related structures. Thirty-four samples were collected from these 38 subjects. CLSM images provided evidence of clustered bacteria in 32 of 33 (97%) of samples. PCR detected the presence of active bacterial DNA signatures in 20 of 31 (65%) of samples. Conclusion PCR and CLSM analysis of fluorescence in situ hybridization-stained samples validates the presence of active bacteria that have formed into a middle ear biofilm that extends across the mucosal layer of the TM. OCT can rapidly and noninvasively identify middle ear biofilms in subjects with severe and persistent cases of otitis media.


Subject(s)
Biofilms , Otitis Media/microbiology , Tympanic Membrane/microbiology , Child , Humans , Otitis Media/diagnostic imaging , Prospective Studies , Tomography, Optical Coherence , Tympanic Membrane/diagnostic imaging
12.
J Biomed Opt ; 22(12): 1-11, 2017 12.
Article in English | MEDLINE | ID: mdl-29275547

ABSTRACT

In an institutional review board-approved study, 25 pediatric subjects diagnosed with chronic or recurrent otitis media were observed over a period of six months with optical coherence tomography (OCT). Subjects were followed throughout their treatment at the initial patient evaluation and preoperative consultation, surgery (intraoperative imaging), and postoperative follow-up, followed by an additional six months of records-based observation. At each time point, the tympanic membrane (at the light reflex region) and directly adjacent middle-ear cavity were observed in vivo with a handheld OCT probe and portable system. Imaging results were compared with clinical outcomes to correlate the clearance of symptoms in relation to changes in the image-based features of infection. OCT images of most all participants showed the presence of additional infection-related biofilm structures during their initial consultation visit and similarly for subjects imaged intraoperatively before myringotomy. Subjects with successful treatment (no recurrence of infectious symptoms) had no additional structures visible in OCT images during the postoperative visit. OCT image findings suggest surgical intervention consisting of myringotomy and tympanostomy tube placement provides a means to clear the middle ear of infection-related components, including middle-ear fluid and biofilms. Furthermore, OCT was demonstrated as a rapid diagnostic tool to prospectively monitor patients in both outpatient and surgical settings.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Otitis Media/diagnostic imaging , Otitis Media/surgery , Postoperative Care/methods , Tomography, Optical Coherence/methods , Child , Humans , Middle Ear Ventilation
13.
J Assoc Res Otolaryngol ; 18(4): 555-568, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28653118

ABSTRACT

Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child's most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.We have developed a technique based on low-coherence interferometry-a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum-to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.


Subject(s)
Otitis Media with Effusion/diagnosis , Otoscopy/methods , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Pilot Projects , Valsalva Maneuver
14.
J Biophotonics ; 10(3): 394-403, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27009636

ABSTRACT

Eustachian tube dysfunction can cause fluid to collect within the middle ear cavity and form a middle ear effusion (MEE). MEEs can persist for weeks or months and cause hearing loss as well as speech and learning delays in young children. The ability of a physician to accurately identify and characterize the middle ear for signs of fluid and/or infection is crucial to provide the most appropriate treatment for the patient. Currently, middle ear infections are assessed with otoscopy, which provides limited and only qualitative diagnostic information. In this study, we propose a method utilizing cross-sectional depth-resolved optical coherence tomography to noninvasively measure the diffusion coefficient and viscosity of colloid suspensions, such as a MEE. Experimental validation of the proposed technique on simulated MEE phantoms with varying viscosity and particulate characteristics is presented, along with some preliminary results from in vivo and ex vivo samples of human MEEs. In vivo Optical Coherence Tomography (OCT) image of a human tympanic membrane and Middle Ear Effusion (MEE) (top), with a CCD image of the tympanic membrane surface (inset). Below is the corresponding time-lapse M-mode OCT data acquired along the white dotted line over time, which can be analyzed to determine the Stokes-Einstein diffusion coefficient of the effusion.


Subject(s)
Ear, Middle/diagnostic imaging , Ear, Middle/physiopathology , Optical Imaging , Otitis Media with Effusion/diagnostic imaging , Otitis Media with Effusion/physiopathology , Algorithms , Equipment Design , Feasibility Studies , Humans , Middle Ear Ventilation , Optical Imaging/instrumentation , Optical Imaging/methods , Otitis Media with Effusion/therapy , Paracentesis , Particle Size , Phantoms, Imaging , Point-of-Care Systems , Viscosity
15.
J Cogn Neurosci ; 27(9): 1723-37, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25848682

ABSTRACT

Information from different modalities is initially processed in different brain areas, yet real-world perception often requires the integration of multisensory signals into a single percept. An example is the McGurk effect, in which people viewing a speaker whose lip movements do not match the utterance perceive the spoken sounds incorrectly, hearing them as more similar to those signaled by the visual rather than the auditory input. This indicates that audiovisual integration is important for generating the phoneme percept. Here we asked when and where the audiovisual integration process occurs, providing spatial and temporal boundaries for the processes generating phoneme perception. Specifically, we wanted to separate audiovisual integration from other processes, such as simple deviance detection. Building on previous work employing ERPs, we used an oddball paradigm in which task-irrelevant audiovisually deviant stimuli were embedded in strings of non-deviant stimuli. We also recorded the event-related optical signal, an imaging method combining spatial and temporal resolution, to investigate the time course and neuroanatomical substrate of audiovisual integration. We found that audiovisual deviants elicit a short duration response in the middle/superior temporal gyrus, whereas audiovisual integration elicits a more extended response involving also inferior frontal and occipital regions. Interactions between audiovisual integration and deviance detection processes were observed in the posterior/superior temporal gyrus. These data suggest that dynamic interactions between inferior frontal cortex and sensory regions play a significant role in multimodal integration.


Subject(s)
Brain/physiology , Motion Perception/physiology , Speech Perception/physiology , Acoustic Stimulation/methods , Electroencephalography , Evoked Potentials , Female , Humans , Lip , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Optical Imaging , Photic Stimulation/methods , Speech , Young Adult
16.
Laryngoscope ; 125(8): E276-82, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25599652

ABSTRACT

OBJECTIVE/HYPOTHESIS: In this study, optical coherence tomography (OCT) is used to noninvasively and quantitatively determine tympanic membrane (TM) thickness and the presence and thickness of any middle-ear biofilm located behind the TM. These new metrics offer the potential to differentiate normal, acute, and chronic otitis media (OM) infections in pediatric subjects. STUDY DESIGN: Case series with comparison group. METHODS: The TM thickness of 34 pediatric subjects was acquired using a custom-built, handheld OCT system following a traditional otoscopic ear exam. RESULTS: Overall thickness (TM and any associated biofilm) was shown to be statistically different for normal, acute, and chronic infection groups (normal-acute and normal-chronic: P value < 0.001; acute-chronic: P value = 0.0016). Almost all observed scans from the chronic group had an accompanying biofilm structure. When the thickness of the TM and biofilm were considered separately in chronic OM, the chronic TM thickness correlated with the normal group (P value = 0.68) yet was still distinct from the acute OM group (P value < 0.001), indicating that the TM in chronic OM returns to relatively normal thickness levels. CONCLUSION: Identifying these physical changes in vivo provides new metrics for noninvasively and quantitatively differentiating normal, acute, and chronic OM. This new diagnostic information has the potential to assist physicians to more effectively and efficiently screen, manage, and refer patients based on quantitative data. LEVEL OF EVIDENCE: 4.


Subject(s)
Ear, Middle/pathology , Otitis Media/diagnosis , Tomography, Optical Coherence/methods , Tympanic Membrane/pathology , Child , Diagnosis, Differential , Humans , Outpatients
17.
J Am Chem Soc ; 136(24): 8536-9, 2014 Jun 18.
Article in English | MEDLINE | ID: mdl-24869475

ABSTRACT

This paper reports a high-throughput, label-free technique to visualize individual carbon nanotubes (CNTs) on a silicon wafer using a conventional optical microscope. We show that individual CNTs can locally enhance the rate of vapor-phase HF etching of SiO2 to produce a SiO2 trench that is several to several tens of nanometers in depth. The trench is visible under an optical microscope due to a change in the optical interference in the SiO2 layer, allowing the location of an individual CNT to be determined. With this technique, we demonstrate high-throughput Raman characterization and reactivity studies on individual CNTs.

18.
Hear Res ; 301: 193-200, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23588039

ABSTRACT

Children with chronic otitis media (OM) often have conductive hearing loss which results in communication difficulties and requires surgical treatment. Recent studies have provided clinical evidence that there is a one-to-one correspondence between chronic OM and the presence of a bacterial biofilm behind the tympanic membrane (TM). Here we investigate the acoustic effects of bacterial biofilms, confirmed using optical coherence tomography (OCT), in adult ears. Non-invasive OCT images are collected to visualize the cross-sectional structure of the middle ear, verifying the presence of a biofilm behind the TM. Wideband measurements of acoustic reflectance and impedance (0.2-6 [kHz]) are used to study the acoustic properties of ears with confirmed bacterial biofilms. Compared to known acoustic properties of normal middle ears, each of the ears with a bacterial biofilm has an elevated power reflectance in the 1 to 3 [kHz] range, corresponding to an abnormally small resistance (real part of the impedance). These results provide assistance for the clinical diagnosis of a bacterial biofilm, which could lead to improved treatment of chronic middle ear infection and further understanding of the impact of chronic OM on conductive hearing loss. This article is part of a special issue entitled "MEMRO 2012".


Subject(s)
Acoustic Impedance Tests/methods , Biofilms , Ear, Middle/microbiology , Tomography, Optical Coherence/methods , Acoustics , Adult , Ear, Middle/pathology , Equipment Design , Hearing Loss, Conductive/prevention & control , Humans , Otitis Media/physiopathology , Otitis Media/therapy , Tympanic Membrane
19.
Ear Hear ; 29(1): 20-32, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18091099

ABSTRACT

OBJECTIVE: Binaural hearing has been shown to support better speech perception in normal-hearing listeners than can be achieved with monaural stimulus presentation, particularly under noisy listening conditions. The purpose of this study was to evaluate whether bilateral electrical stimulation could confer similar benefits for cochlear implant listeners. DESIGN: A total of 26 postlingually deafened adult patients with short duration of deafness were implanted at five centers and followed up for 1 yr. Subjects received MED-EL COMBI 40+ devices bilaterally; in all but one case, implantation was performed in a single-stage surgery. Speech perception testing included CNC words in quiet and CUNY sentences in noise. Target speech was presented at the midline (0 degrees), and masking noise, when present, was presented at one of three simulated source locations along the azimuth (-90, 0, and +90 degrees). RESULTS: Benefits of bilateral electrical stimulation were observed under conditions in which the speech and masker were spatially coincident and conditions in which they were spatially separated. Both the "head shadow" and "summation" effects were evident from the outset. Benefits consistent with "binaural squelch" were not reliably observed until 1 yr after implantation. CONCLUSIONS: These results support a growing consensus that bilateral implantation provides functional benefits beyond those of unilateral implantation. Longitudinal data suggest that some aspects of binaural processing continue to develop up to 1 yr after implantation. The squelch effect, often reported as absent or rare in previous studies of bilateral cochlear implantation, was present for most subjects at the 1 yr measurement interval.


Subject(s)
Cochlear Implantation , Deafness/surgery , Speech Perception/physiology , Adult , Aged , Electric Stimulation/instrumentation , Female , Humans , Male , Middle Aged , Time Factors , Vocabulary
20.
Otol Neurotol ; 28(5): 609-14, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17514064

ABSTRACT

OBJECTIVE: This study compared preoperative and postoperative cochlear implant benefit in subjects with steeply sloping high-frequency hearing losses (HLs) who were implanted with standard long cochlear implant electrodes to: 1) determine the effect of etiology, 2) compare outcomes in studies exploring the use of combined electrical and acoustic stimulation, and 3) compare outcomes in patients implanted using standard criteria. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Nine adults with steeply sloping high-frequency congenital (n=2) or acquired (n=7) bilateral sensorineural HL. All pure-tone audiograms fit the criteria for trials of a short electrode aimed at preserving low-frequency acoustic hearing. INTERVENTION: Subjects received full insertion of a standard cochlear implant long electrode in the poorer ear. MAIN OUTCOME MEASURES: Preoperative versus postoperative audiograms, word and sentence recognition in quiet and noise. RESULTS: Patients with progressive acquired HLs experienced significantly improved speech understanding in quiet and in noise with the cochlear implant, especially when combined with hearing aid use in the contralateral ear. Patients with congenital HLs experienced little or no improvement in the implanted ear when tested with the implant alone, but achieved some benefit when the implant was combined with a hearing aid in the nonimplanted ear. CONCLUSION: Based on this small sample, patients with acquired steeply sloping high-frequency HLs obtain significant benefit from cochlear implantation with standard long electrodes. In progressive losses, full insertion of a long electrode would be preferable to a short electrode because acoustic hearing may diminish over time. In contrast, patients with congenital losses may not benefit from long electrodes, and might be better served by implanting a short electrode, thereby allowing use of low-frequency acoustic stimulation.


Subject(s)
Acoustic Stimulation/instrumentation , Cochlear Implantation/instrumentation , Cochlear Implants , Hearing Loss, High-Frequency/rehabilitation , Adult , Aged , Audiometry, Pure-Tone , Auditory Threshold/physiology , Combined Modality Therapy , Electric Stimulation/instrumentation , Female , Hearing Loss, High-Frequency/diagnosis , Humans , Male , Middle Aged , Postoperative Care/instrumentation , Preoperative Care/instrumentation , Retrospective Studies , Severity of Illness Index , Speech Perception/physiology
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