Optical Coherence Tomography (OCT) has shown its detection and diagnostic capabilities for otitis media (OM), enabling visualization through scattering tissues including the tympanic membrane and biofilms, and into the middle ear cavity. Preliminary results from an ongoing five-year 235-subject study at Children’s Wisconsin, Medical College of Wisconsin, are presented. A vision-language machine learning model was trained on OCT image features and clinical metadata to differentiate OM disease states and predict required interventions. This study demonstrates the prognostic value of OCT in assessing OM and offers the potential for improving the management of patients with OM.
Nonlinear microscopy encompasses a range of imaging techniques that leverage laser technology to reveal the chemical composition and structure of a sample. Nonlinear microscopes exploit femtosecond laser pulses to target intrinsic biomolecules of cells and tissues. Fiber lasers have limited bandwidth and reduced wavelength tunability, leading to long pulse durations and limited molecular applications. Supercontinuum generation solves this problem, enabling <50 fs pulses and a larger range of molecular excitation. This paper presents nonlinear microscopy with supercontinuum generation from a Yttrium Aluminum Garnet (YAG) crystal enabling simultaneous label-free autofluorescence multi-harmonic (SLAM) microscopy with high resolution and specificity in biological tissues.
Biofilms are persistent microbial communities that play a significant role in middle ear pathologies. Spectral domain (SD)-OCT has been used to detect biofilms in the middle ear during otitis media. However, it cannot measure birefringence or probe deeper regions of the middle ear cavity. A polarization-sensitive swept-source OCT system has been developed to image in vitro biofilms and cholesteatoma to enhance identification and classification of these pathologies. Biofilms were grown on tympanic membranes and ossicles to assess for changes in birefringence. A handheld probe is being developed to compare against a library of in vivo SD-OCT images.
SignificanceNeuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions.AimWe aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation.ApproachA sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model k-values in experimental groups: sham control (SC, n = 5, 0.0 mA / 0 Hz), stimulation level 1 (SL1, n = 5, 3.4 mA / 50 Hz, and k = 2.57), and stimulation level 2 (SL2, n = 5, 6.8 mA / 100 Hz, and k = 3.17).ResultsThe stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of +4 % / − 309 % (SL1/SL2) in phase retardation and −79 % / − 148 % in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a +1 % / − 36 % difference in myelin pixel counts and −13 % / + 29 % difference in axon pixel counts, and an overall increase in cell nuclei pixel count of +20 % / + 35 % . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis.ConclusionsThe poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.
Earwax or cerumen is a substance secreted by the ceruminous and sebaceous glands of the ear canal. The main function of this biofluid is as a physical barrier, but its buildup can lead to earwax impaction and result in hearing loss. Optical coherence tomography (OCT) is one potential method for assessing earwax. A catheter-based OCT system with a handheld probe and custom-made 3D-printed specula was designed and used to non-invasively acquire cross-sectional and volumetric images of the canal of adult human subjects. Features relating to quantity, structure, texture, and optical attenuation were extracted and correlated back to subjects’ ear health.
Otitis media (OM) is a common disease of the middle ear, with 80% of children experiencing an infection before age three. Diagnostic methods rely on interpretation of symptoms from an otoscope, which help physicians visualize the eardrum. To provide precise structural and biochemical information, a prototype non-contact multimodal Raman spectroscopy (RS) and optical coherence tomography (OCT) system and handheld probe were created. Observation of in vitro physiologically-relevant ear models and comparison to in vivo scans from pediatric subjects presenting with OM detail application-specific development. Design challenges for clinical use, including maximum permissible exposure and physical size constraints, are presented.
Otitis media (OM) is a common middle ear disease that is treated with antibiotics. However, over-prescription of antibiotics heightens the risk of antibiotic resistance. Here, we report the development and testing of a new cold microplasma (CMP) device to treat OM, and demonstrate the translation for in vivo use in a chinchilla animal model. In vitro nontypeable Haemophilus influenzae bacterial and biofilm samples and ex vivo tissue specimens were evaluated for inactivation and injury. CMP-induced effects on any infectious symptoms (middle ear fluid, biofilms) were longitudinally observed with OCT. This represents the first application of CMP treatments for OM therapy.
KEYWORDS: Optical coherence tomography, Biological research, Ear, In vitro testing, Image analysis, Principal component analysis, In vivo imaging, Feature extraction, Binary data
Otitis media (OM) is a prevalent disease among children worldwide. Antibiotic-resistant bacterial biofilms can develop in the middle ear during recurrent/chronic ear infections. OCT was used to compare microstructural texture features from primary bacterial biofilms in vitro. From 1200 ROI images of each biofilm class, 934 texture features were extracted. Principle component analysis and five-fold cross-validation were performed using Support vector machines (SVMs). Currently, the model has achieved 0.97 AUC (cubic kernel function) and an average classification accuracy of 89%. Texture analysis of bacterial biofilm OCT images with SVM may enable real-time visualization and differentiation of OM-causing bacterial biofilms in vivo.
Otitis media or middle-ear infection is a widespread bacterial/viral disease. Antibiotic-resistant bacteria within biofilms emerge during chronic ear infections and are challenging to treat. We explored Raman spectroscopy (RS) and Optical Coherence Tomography (OCT) to identify and compare unique spectroscopic and microstructural features from primary otopathogenic bacteria in colony, planktonic, and biofilm forms, in vitro. RS was utilized to identify biochemical fingerprints and OCT was used to generate depth-resolved 2D and 3D images to compare refractive indices and optical attenuation coefficients. A combined RS-OCT system will enable real-time visualization and diagnosis of bacterial OM at the point-of-care.
A biofilm morphology transition is a dynamic process that mediates growth and dispersion. The development of the dynamic process shows the enhancement of the power-law tail that is observed while the biofilms grown at the air-agar interface are submerged in a medium. Environmentally driven morphology transitions of biofilm were analyzed by acquiring the phase displacements of the Doppler shift and linearly decomposed by ballistic (Cauchy) and diffusive (Gaussian) distributions. The analysis provides the internal dynamic characteristics of biofilm that pave the way between the conventional dynamic parameters and the anomalous diffusion parameters.
A middle ear infection is a prevalent inflammatory disease during childhood, often caused by bacterial pathogens. A portable and replaceable microplasma jet array was developed to investigate the feasibility of inactivating Pseudomonas aeruginosa, a common bacterial strain associated with middle ear infections. Reactive species generated by the non-thermal microplasma jet array inactivated planktonic bacteria and biofilm. A middle ear phantom was developed using the rat eardrum to study the antimicrobial effects on bacteria located behind the eardrum. Lastly, 3D volumetric OCT imaging and histology were performed on the rat eardrum to examine the potential structural changes due to the plasma.
Middle ear effusions (MEEs) are accumulated middle ear secretions or fluid behind the eardrum during otitis media (OM). A portable, handheld OCT system was developed to non-invasively investigate various optical scattering properties of MEEs in pediatric subjects. Furthermore, clinically relevant parameters of MEEs, including viscosity and bacterial load, were measured from the extracted MEEs after the surgical procedure to treat OM. In vivo OCT images of the middle ear prior to the surgery, OCT images of the extracted MEEs, and biological parameters were correlated to determine the relationship between the optical signatures in MEEs and the clinical findings of OM.
KEYWORDS: Optical coherence tomography, In vivo imaging, Bacteria, Image analysis, Pathogens, Resistance, 3D image processing, Stereoscopy, Human subjects, Luminescence
Mechanical ventilation is a critical intervention given to intensive care unit (ICU) patients who need airway support. However, this intervention with an endotracheal tube (ETT) is associated with complications such as ventilator-associated pneumonia (VAP). VAP is reported to develop within 48 hours after intubation and is associated with a mortality rate between 20 to 50%. The formation of bacterial biofilms within these ETT tubes provides a niche for infectious bacteria to become resistant to antibiotics. Suctioning of the ETT is believed to prevent airway colonization by pathogens, reduce resistance to airflow, and decrease biofilm formation. However, reports have shown that standard-of-care suctioning is not adequate to eliminate secretions from the ETT, and additional measures aiming to reduce the formation of ETT biofilms have been proposed to reduce VAP. We have recently demonstrated the use of catheter-based 3-D OCT imaging to identify the presence of in vivo biofilms within the ETTs of intubated human subjects in the ICU. In this study, we quantify the volume of mucus and biofilm in ETTs in intubated ICU patients using 3-D OCT, and define the efficacy of suctioning. Longitudinal OCT imaging was performed daily before and after suctioning at approximately 24-hour intervals until extubation. Extubated ETTs were subsequently imaged for further analysis. OCT image analysis results were correlated with clinical data and fluorescence microscopy/Gram stain images to verify the presence of bacteria and biofilm. In vivo catheter-based 3-D OCT offers the potential to rapidly determine the efficacy of ETT suctioning in order to effectively compare suctioning and brushing strategies in an effort to reduce the incidence of VAP.
Otitis media (OM) is a common ear infection and a leading cause of conductive hearing loss in the pediatric population. Current technologies 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 presence of biofilm or fluid formed behind the tympanic membrane (TM). Our group has developed handheld probes and portable optical coherence tomography (OCT) systems that have been used in various clinical studies to provide quantitative information about structural changes, and thus accurately characterize OM. Further, an automated machine learning-based approach from our group has been developed and integrated to classify OCT images associated with various stages of OM, without the need for interpretation by an expert reader.
In this study, we report a portable, low-cost, briefcase OCT system with automated classification for point-of-care diagnosis of OM. The briefcase OCT system cost < $8000USD with a 5-fold cost reduction and a 3-fold size reduction, compared to more standard OCT systems. Additionally, this system utilizes unique real-time mosaicking of surface video images that are synchronized with rapid A-scan acquisition, enabling computationally generated thickness maps and construction of cross-sectional B-mode images over extended lateral distances. Furthermore, a random-forest based classifier is utilized with an expanded feature set based on various statistics and metrics derived from OCT A-lines and B-scans. This system will help physicians and untrained users to collect OCT data and receive a diagnostic prediction indicating the presence and type of OM, potentially leading to more accurate point-of-care diagnoses.
Development of low-cost and portable optical coherence tomography (OCT) systems is of global interest in the OCT research community. Such systems enable utility broadly throughout a clinical facility, or in remote areas that often lack clinical infrastructure. We report the development and validation of a low-cost, portable briefcase spectral-domain optical coherence tomography (SD-OCT) system for point-of-care diagnostics in primary care centers and/or in remote settings. The self-contained briefcase OCT contains all associated optical hardware, including light source, spectrometer, hand-held probe, and a laptop. Additionally, this system utilizes unique real-time mosaicking of surface video images that are synchronized with rapid A-scan acquisition to eliminate the need for lateral scanning hardware, and enable the construction of cross-sectional B-mode images over extended lateral distances. The entire briefcase system weighs 9 kg and costs ∼USD$8000 using off-the-shelf components. System performance was validated by acquiring images of in vivo human skin on the fingertip, palm, and nail fold. The efficiency, portability, and low-cost enable accessibility and utility in primary care centers and low-resource settings.
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.
Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.
We investigate and demonstrate the feasibility of using a combined Raman scattering (RS) spectroscopy and low-coherence interferometry (LCI) probe to differentiate microbial pathogens and improve our diagnostic ability of ear infections [otitis media (OM)]. While the RS probe provides noninvasive molecular information to identify and differentiate infectious microorganisms, the LCI probe helps to identify depth-resolved structural information as well as to guide and monitor positioning of the Raman spectroscopy beam for relatively longer signal acquisition times. A series of phantom studies, including the use of human middle ear effusion samples, were performed to mimic the conditions of in vivo investigations. These were also conducted to validate the feasibility of using this combined RS/LCI probe for point-of-care diagnosis of the infectious pathogen(s) in OM patients. This work establishes important parameters for future in vivo investigations of fast and accurate determination and diagnosis of infectious microorganisms in OM patients, potentially improving the efficacy and outcome of OM treatments, and importantly reducing the misuse of antibiotics in the presence of viral infections.
Otitis media (OM) is a highly prevalent disease that can be caused by either a bacterial or viral infection. Because antibiotics are only effective against bacterial infections, blind use of antibiotics without definitive knowledge of the infectious agent, though commonly practiced, can lead to the problems of potential harmful side effects, wasteful misuse of medical resources, and the development of antimicrobial resistance. In this work, we investigate the feasibility of using a combined Raman scattering spectroscopy and low coherence interferometry (LCI) device to differentiate OM infections caused by viruses and bacteria and improve our diagnostic ability of OM. Raman spectroscopy, an established tool for molecular analysis of biological tissue, has been shown capable of identifying different bacterial species, although mostly based on fixed or dried sample cultures. LCI has been demonstrated recently as a promising tool for determining tympanic membrane (TM) thickness and the presence and thickness of middle-ear biofilm located behind the TM. We have developed a fiber-based ear insert that incorporates spatially-aligned Raman and LCI probes for point-of-care diagnosis of OM. As shown in human studies, the Raman probe provides molecular signatures of bacterial- and viral-infected OM and normal middle-ear cavities, and LCI helps to identify depth-resolved structural information as well as guide and monitor positioning of the Raman spectroscopy beam for relatively longer signal acquisition time. Differentiation of OM infections is determined by correlating in vivo Raman data collected from human subjects with the Raman features of different bacterial and viral species obtained from cultured samples.
Tympanic membrane (TM) thickness can provide crucial information for diagnosing several middle ear pathologies. An imaging system integrating low coherence interferometry (LCI) with the standard video otoscope has been shown as a promising tool for quantitative assessment of in-vivo TM thickness. The small field-of-view (FOV) of TM surface images acquired by the combined LCI-otoscope system, however, makes the spatial registration of the LCI imaging sites and their location on the TM difficult to achieve. It is therefore desirable to have a tool that can map the imaged points on to an anatomically accurate full-field surface image of the TM. To this end, we propose a novel automated mosaicking algorithm for generating a full-field surface image of the TM with co-registered LCI imaging sites from a sequence of multiple small FOV images and corresponding LCI data. Traditional image mosaicking techniques reported in the biomedical literature, mostly for retinal imaging, are not directly applicable to TM image mosaicking because unlike retinal images, which have several distinctive features, TM images contain large homogeneous areas lacking in sharp features. The proposed algorithm overcomes these challenges of TM image mosaicking by following a two-step approach. In the first step, a coarse registration based on the correlation of gross image features is performed. Subsequently, in the second step, the coarsely registered images are used to perform a finer intensity-based co-registration. The proposed algorithm is used to generate, for the first time, full-field thickness distribution maps of in-vivo human TMs.
Otolaryngologists utilize a variety of diagnostic techniques to assess middle ear health. Tympanometry, audiometry, and otoacoustic emissions examine the mobility of the tympanic membrane (eardrum) and ossicles using ear canal pressure and auditory tone delivery and detection. Laser Doppler vibrometry provides non-contact vibrational measurement, and acoustic reflectometry is used to assess middle ear effusion using sonar. These technologies and techniques have advanced the field beyond the use of the standard otoscope, a simple tissue magnifier, yet the need for direct visualization of middle ear disease for superior detection, assessment, and management remains.
In this study, we evaluated the use of portable optical coherence tomography (OCT) and pneumatic low-coherence interferometry (LCI) systems with handheld probe delivery to standard tympanometry, audiometry, otoacoustic emissions, laser Doppler vibrometry, and acoustic reflectometry. Comparison of these advanced optical imaging techniques and current diagnostics was conducted with a case study subject with a history of unilateral eardrum trauma. OCT and pneumatic LCI provide novel dynamic spatiotemporal structural data of the middle ear, such as the thickness of the eardrum and quantitative detection of underlying disease pathology, which could allow for more accurate diagnosis and more appropriate management than currently possible.
We report the development of a low-cost hand-held optical coherence imaging system. The proposed system is based on the principle of linear optical coherence tomography (Linear OCT), a technique which was proposed in the early 2000s as a simpler alternative to the conventional time-domain and Fourier-domain OCT. In our design, as in the traditional Michaelson interferometer, light from a broadband source is split into sample and reference beams. Unlike in a Michaelson interferometer though, upon return, a tilt is introduced to the reference beam before it is combined with the sample beam to illuminate a detector array. The resulting fringe pattern encodes information about the relative time-of-flight of photons between the sample and reference arms, which can be decoded by standard signal processing techniques to obtain depth resolved reflectivity profiles of the sample. The axial resolution and the SNR of our system was measured to be approximately 5.2 μm and 80 dB, respectively. The performance of the proposed system was compared with a standard state-of-the-art Fourier-domain low coherence interferometry (LCI) system by imaging several biological and non-biological samples. The results of this study indicate that the proposed low-cost system might be a suitable choice for applications where the imaging depth and SNR can be traded for lower cost and simpler optical design. Two potentially useful applications of the proposed imaging system could be for imaging the human tympanic membrane (TM) for diagnosing middle ear pathologies, and to visualize the sub-surface features of materials for non-destructive evaluation and quality inspection.
Breast-conserving surgery is a frequent option for women with stage I and II breast cancer, and with radiation treatment,
can be as effective as a mastectomy. However, adequate margin detection remains a challenge, and too often additional
surgeries are required. Optical coherence tomography (OCT) provides a potential method for real-time, high-resolution
imaging of breast tissue during surgery. Intra-operative OCT imaging of excised breast tissues has been previously
demonstrated by several groups. In this study, a novel handheld surgical probe-based OCT system is introduced, which
was used by the surgeon to image in vivo, within the tumor cavity, and immediately following tumor removal in order to
detect the presence of any remaining cancer. Following resection, study investigators imaged the excised tissue with the
same probe for comparison. We present OCT images obtained from over 15 patients during lumpectomy and
mastectomy surgeries. Images were compared to post-operative histopathology for diagnosis. OCT images with micron
scale resolution show areas of heterogeneity and disorganized features indicative of malignancy, compared to more
uniform regions of normal tissue. Video-rate acquisition shows the inside of the tumor cavity as the surgeon sweeps the
probe along the walls of the surgical cavity. This demonstrates the potential of OCT for real-time assessment of surgical
tumor margins and for reducing the unacceptably high re-operation rate for breast cancer patients.
The transition of optical coherence tomography (OCT) technology from the lab environment towards the more challenging clinical and point-of-care settings is continuing at a rapid pace. On one hand this translation opens new opportunities and avenues for growth, while on the other hand it also presents a new set of challenges and constraints under which OCT systems have to operate. OCT systems in the clinical environment are not only required to be user friendly and easy to operate, but should also be portable, have a smaller form factor coupled with low cost and reduced power consumption. Digital signal processors (DSP) are in a unique position to satisfy the computational requirements for OCT at a much lower cost and power consumption compared to the existing platforms such as CPU and graphics processing units (GPUs). In this work, we describe the implementation of optical coherence tomography (OCT) and interferometric synthetic aperture microscopy (ISAM) processing on a floating point multi-core DSP (C6678, Texas Instruments). ISAM is a computationally intensive data processing technique that is based on the re-sampling of the Fourier space of the data to yield spatially invariant transverse resolution in OCT. Preliminary results indicate that 2DISAM processing at 70,000 A-lines/sec and OCT at 180,000 A-lines/sec can be achieved with the current implementation using available DSP hardware.
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