Handheld Briefcase Optical Coherence Tomography with Real-Time Machine Learning Classifier for Middle Ear Infections.

A middle ear infection is a prevalent inflammatory disease most common in the pediatric population, and its financial burden remains substantial. Current diagnostic methods are highly subjective, relying on visual cues gathered by an otoscope. To address this shortcoming, optical coherence tomography (OCT) has been integrated into a handheld imaging probe. This system can non-invasively and quantitatively assess middle ear effusions and identify the presence of bacterial biofilms in the middle ear cavity during ear infections. Furthermore, the complete OCT system is housed in a standard briefcase to maximize its portability as a diagnostic device. Nonetheless, interpreting OCT images of the middle ear more often requires expertise in OCT as well as middle ear infections, making it difficult for an untrained user to operate the system as an accurate stand-alone diagnostic tool in clinical settings. Here, we present a briefcase OCT system implemented with a real-time machine learning platform for middle ear infections. A random forest-based classifier can categorize images based on the presence of middle ear effusions and biofilms. This study demonstrates that our briefcase OCT system coupled with machine learning can provide user-invariant classification results of middle ear conditions, which may greatly improve the utility of this technology for the diagnosis and management of middle ear infections.

Efficacy of endotracheal tube suctioning in intubated intensive care unit patients determined by in vivo catheter-based optical coherence tomography-a pilot study.

BACKGROUND: Mechanical ventilation using an endotracheal tube (ETT) is one of the critical interventions given to patients in the intensive care unit (ICU). ETTs are associated with the formation of biofilms, placing patients at increased risk for developing ventilator-associated pneumonia (VAP). ETT suctioning is used to remove secretions, reduce bacterial colonization, and reduce the rate of biofilm formation. However, current standard-of-care suctioning procedures do not adequately eliminate all secretions from the ETT. METHODS: This observational study was conducted in a cohort of 4 subjects admitted to the ICU and intubated with an ETT, irrespective of ethnicity, gender, or race. A total of 23 suctioning procedures were evaluated with in vivo three-dimensional (3D) optical coherence tomography (OCT) imaging, before and after suctioning. A secretion density metric was derived from the OCT data to quantify the amount of secretions present within the ETT, and an attenuation coefficient metric was derived to detect and quantify the presence of biofilms. Analyzed OCT images were correlated with clinical and microscopy data. RESULTS: Data obtained suggests that the current standard-of-care suctioning procedure is inefficient at clearing secretions or preventing the formation of biofilms. The presence of biofilms was corroborated with both post-intubation microscopy of the ETTs, as well as with clinical data. CONCLUSIONS: We conclude that the standard-of-care suctioning method does not eliminate secretions nor reduce the formation of biofilm in ETTs. Our in situ imaging method was sensitive to the presence of secretions, biofilms, and quantitative, and can be used for investigating different suctioning protocols in the future.

Development of a Smartphone-Based Skin Simulation Model for Medical Education.

INTRODUCTION: Teaching dermatology to medical students entails a series of lectures, pictures, and hands-on skin examinations to convey a sense of skin features and textures, often by use of simulated skin models. However, such methods can often lack accurate visual and tactile texture representation of skin lesions. To facilitate learning, we have developed a smartphone-based skin simulation model, which provides a configurable visual and tactile sense of a lesion by using the ubiquitous availability of smartphone-based mobile platforms. METHODS: A polydimethylsiloxane (PDMS) overlay was used as a configurable translucent elastomer material to model the stiffness and texture of skin. A novel custom smartphone-based app was developed to capture images of various skin lesions, which were subsequently displayed on a tablet or second smartphone, over which the PDMS model skin elastomer was placed. Using the local Bluetooth connection between mobile devices, an iterative feedback algorithm corrected the visual distortion caused by the optical scattering of the translucent elastomer, enabling better virtual visualization of the lesion. RESULTS: The developed smartphone-based app corrected the distortion of images projected through the simulated skin elastomer. Surface topography of the developed PDMS elastomer provided a more accurate representation of skin texture. CONCLUSIONS: In this investigation, we developed a smartphone-based skin lesion visualization app with a simulated skin elastomer for training/education in not only dermatology but also all general medical specialties that examine the skin. This technique has the potential to advance the educational experience by giving students the ability to see, touch, and feel pragmatic skin textures and lesions.

Polymaleimide-Based Polysulfobetaines Bearing Functional and Nonfunctional Hydrophobic Units and Its Aggregation Behavior in Aqueous Media.

Copolymaleimide-based zwitterionic polysulfobetaines (PM-SBs) were prepared by a "top down" method for the first time. Interfacial studies of these polymers showed many interesting characteristics. These PM-SBs did not require any salt in the form of sodium chloride (NaCl) to dissolve in water and exhibited exceptional salt tolerance. PM-SBs showed very mild thermogelling behavior. The viscosity of 5 wt % aqueous solution of polymers increased with increasing concentration of salt without showing any limits within the salt concentrations studied [200g/L of NaCl (3.4 M)] in contrast to other reported zwitterionic polysulfobetaines. Dynamic light scattering (DLS) studies also indicated a structure-dependent particle size with varying concentrations of NaCl solution. The uniformity of particles of 5 wt % aqueous solution of PM-SBs increased with increasing concentration of NaCl. At 0.1 wt % concentration, even in the absence of NaCl, mild aggregation was noticed. The concentration of aggregated particles increased with the increasing concentration of NaCl. Because of the exceptionally high salt tolerance, these polymers are potentially suitable for applications in antifouling, oil field, personal care formulations, and water purification.

Automated classification platform for the identification of otitis media using optical coherence tomography.

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.

In vivo detection of endotracheal tube biofilms in intubated critical care patients using catheter-based optical coherence tomography.

The formation of biofilms in the endotracheal tubes (ETTs) of intubated patients on mechanical ventilation is associated with a greater risk of ventilator-associated pneumonia and death. New technologies are needed to detect and monitor ETTs in vivo for the presence of these biofilms. Longitudinal OCT imaging was performed in mechanically ventilated subjects at 24-hour intervals until extubation to detect the formation and temporal changes of in vivo ETT biofilms. OCT-derived attenuation coefficient images were used to differentiate between mucus and biofilm. Extubated ETTs were examined with optical and electron microscopy, and all imaging results were correlated with standard-of-care clinical test reports. OCT and attenuation coefficient images from four subjects were positive for ETT biofilms and were negative for two subjects. The processed and stained extubated ETTs and clinical reports confirmed the presence/absence of biofilms in all subjects. Our findings confirm that OCT can detect and differentiate between biofilm-positive and biofilm-negative groups (P < 10-5 ). OCT image-based features may serve as biomarkers for direct in vivo detection of ETT biofilms and help drive investigation of new management strategies to reduce the incidence of VAP.

Economical and compact briefcase spectral-domain optical coherence tomography system for primary care and point-of-care applications.

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 vivo detection of nanometer-scale structural changes of the human tympanic membrane in otitis media.

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.

Pneumatic low-coherence interferometry otoscope to quantify tympanic membrane mobility and middle ear pressure.

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.

Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements.

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.

Panel strain of Klebsiella pneumoniae for beta-lactam antibiotic evaluation: their phenotypic and genotypic characterization.

Klebsiella pneumoniae is responsible for numerous infections caused in hospitals, leading to mortality and morbidity. It has been evolving as a multi-drug resistant pathogen, acquiring multiple resistances such as such as horizontal gene transfer, transposon-mediated insertions or change in outer membrane permeability. Therefore, constant efforts are being carried out to control the infections using various antibiotic therapies. Considering the severity of the acquired resistance, we developed a panel of strains of K. pneumoniae expressing different resistance profiles such as high-level penicillinase and AmpC production, extended spectrum beta-lactamases and carbapenemases. Bacterial strains expressing different resistance phenotypes were collected and examined for resistance genes, mutations and porin alterations contributing to the detected phenotypes. Using the Massive parallel sequencing (MPS) technology we have constructed and genotypically characterized the panel strains to elucidate the multidrug resistance. These panel strains can be used in the clinical laboratory as standard reference strains. In addition, these strains could be significant in the field of pharmaceuticals for the antibiotic drug testing to verify its efficiency on pathogens expressing various  resistances.

Molecular epidemiology and resistome analysis of multidrug-resistant ST11 Klebsiella pneumoniae strain containing multiple copies of extended-spectrum ß-lactamase genes using whole-genome sequencing.

The aim of this work was to investigate the mechanism responsible for multidrug resistance in ST11 Klebsiella pneumoniae YMC 2013/7/B3993 containing multiple copies of ESBL genes using multiple parallel sequencing technology. In-depth analysis of the strain revealed multiple copies of ESBL genes, 2 copies of blaSHV-12 and 1 copy of blaCTX-M-15. Furthermore, 1 copy of blaOXA-9 and 3 copies of blaTEM-1 were found. The insertion of Tn1331 was detected, which consisted of blaOXA-9, blaTEM-1, aac(6')-lb-cr, and aadA1 genes. The acquisition of multiple copies of resistance genes was due to the insertion of transposons in the bacterial genome and plasmid. The genotypic analysis revealed that the isolates belonging to ST11 showed severe resistance phenotypes and greater dissemination potential. To the best of our knowledge, this is the first report demonstrating multiple copies of same ESBL genes in K. pneumoniae ST11 isolate. Furthermore, massive parallel sequencing studies of genetic factors to enhance the fitness of this type strain would be warranted to determine whether ST11 K. pneumoniae can spread the KPC-type gene.

Development of a first-generation miniature multiple reference optical coherence tomography imaging device.

Multiple reference optical coherence tomography (MR-OCT) is a technology ideally suited to low-cost, compact OCT imaging. This modality is an extension of time-domain OCT with the addition of a partial mirror in front of the reference mirror. This enables extended, simultaneous depth scanning with the relatively short scan range of a miniature voice coil motor on which the scanning mirror is mounted. This work details early stage development of the first iteration of a miniature MR-OCT device. This iteration utilizes a fiber-coupled input from an off-board superluminescent diode. The dimensions of the module are 40 × 57 ?? mm . Off-the-shelf miniature optical components, voice coil motors, and photodetectors are used, with the complexity of design depending on the specific application. The photonic module can be configured as either polarized or nonpolarized and can include balanced detection. The results shown in this work are from the nonpolarized device. The system was characterized through measurement of the input spectrum, axial resolution, and signal-to-noise ratio. Typical B-scans of static and in vivo samples are shown, which illustrate the potential applications for such a technology.

Assessment of curing behavior of light-activated dental composites using intensity correlation based multiple reference optical coherence tomography.

BACKGROUND AND OBJECTIVES: Monitoring the curing kinetics of light-activated resin is a key area of research. These resins are used in restorative applications and particularly in dental applications. They can undergo volumetric shrinkage due to poor control of the depth dependent curing process, modulated by the intensity and duration of the curing light source. This often results in the formation of marginal gaps, causing pain and damage to the restoration site. In this study, we demonstrate the capabilities of a correlation method applied using a multiple references optical coherence tomography (MR-OCT) architecture to monitor the curing of the resin. STUDY DESIGN/MATERIALS AND METHODS: A MR-OCT system is used in this study to monitor the curing of the resin. The system operates at the center wavelength of 1310 nm with an A-scan rate of 1200 A-scans per second. The axial and lateral resolution of the system is ∼13 µm and ∼27 µm. The method to determine the intensity correlation between adjacent B-frames is based on the Pearson correlation coefficient for a region of interest. Calculating the correlation coefficient for multiple B-frames related to the first B-frame at regular spaced time points, shows for a noncured resin a reduction of the correlation coefficient over time due to Brownian motion. The time constant of the reduction of the correlation value is a measure for the progress of the polymerization during LED light irradiation of the resin. The proposed approach is potentially a low-cost, powerful and unique optical imaging modality for measuring the curing behavior of dental resin and other resins, coatings, and adhesives in medical and industrial applications. RESULTS: To demonstrate the proposed method to monitor the curing process, a light-activated resin composite from GRADIA DIRECT ANTERIOR (GC Corporation, Japan) is studied. The curing time of resin was measured and monitored as a function of depth. The correlation coefficient method is highly sensitive to Brownian motion. The process of curing results in a change in intensity as measured by the MR-OCT signal and hence can be monitored using this method. CONCLUSIONS: These results show that MR-OCT has the potential to measure the curing time and monitor the curing process as a function of depth. Moreover, MR-OCT as a product has potential to be compact, low-cost and to fit into a smartphone. Using such a device for monitoring the curing of the resin will be suitable for dentists in stationary and mobile clinical settings.

3D nondestructive testing system with an affordable multiple reference optical-delay-based optical coherence tomography.

Optical coherence tomography (OCT) is emerging as a powerful noncontact imaging technique, allowing high-quality cross-sectional imaging of scattering specimens nondestructively. However, the complexity and cost of current embodiments of an OCT system limit its use in various nondestructive testing (NDT) applications at resource-limited settings. In this paper, we demonstrate the feasibility of a novel low-cost OCT system for a range of nondestructive testing (NDT) applications. The proposed imaging system is based on an enhanced time-domain OCT system with a low cost and small form factor reference arm optical delay, called multiple reference OCT (MR-OCT), which uses a miniature voice coil actuator and a partial mirror for extending the axial scan range. The proposed approach is potentially a low-cost, compact, and unique optical imaging modality for a range of NDT applications in a low-resource setting. Using this method, we demonstrated the capability of MR-OCT to perform cross-sectional and volumetric imaging at 1200 A-scans per second.

Dermascope guided multiple reference optical coherence tomography.

In this paper, we report the feasibility of integrating a novel low cost optical coherence tomography (OCT) system with a dermascope for point-of-care applications. The proposed OCT system is based on an enhanced time-domain optical coherence tomographic system, called multiple reference OCT (MR-OCT), which uses a single miniature voice coil actuator and a partial mirror for extending the axial scan range. The system can simultaneously register both the superficial dermascope image and the depth-resolved OCT sub-surface information by an interactive beam steering method. A practitioner is able to obtain the depth resolved information of the point of interest by simply using the mouse cursor. The proposed approach of combining a dermascope with a low cost OCT provides a unique powerful optical imaging modality for a range of dermatological applications. Hand-held dermascopic OCT devices would also enable point of care and remote health monitoring.

Feasibility of correlation mapping optical coherence tomography (cmOCT) for anti-spoof sub-surface fingerprinting.

We propose the use of correlation mapping optical coherence tomography (cmOCT) to deliver additional biometrics associated with the finger that could complement existing fingerprint technology for law enforcement applications. The current study extends the existing fingerprint paradigm by measuring additional biometrics associated with sub-surface finger tissue such as sub-surface fingerprints, sweat glands, and the pattern of the capillary bed to yield a user-friendly cost effective and anti-spoof multi-mode biometric solution associated with the finger. To our knowledge no other method has been able to capture sub-surface fingerprint, papillary pattern and horizontal vessel pattern in a single scan or to show the correspondence between these patterns in live adult human fingertip. Unlike many current technologies this approach incorporates 'liveness' testing by default. The ultimate output is a biometric module which is difficult to defeat and complements fingerprint scanners that currently are used in border control and law enforcement applications.