The retinal vasculature has plexuses at multiple depths, interconnected in a complex pattern. While optical coherence tomography angiography (OCTA) visualizes the vasculature at the capillary level, creating a 3D representation of the vasculature, including the connections between plexuses, remains a challenge. Here, we employ Optimally Oriented Flux (OOF) on retinal OCTA to simultaneously preserve the inter-plexus connections and suppress projection artifacts, facilitating high-contrast 3D visualization of the vasculature. Furthermore, a novel framework is developed to transform the vasculature into a graph, which enables quantification of ‘importance’ of each capillary using betweenness centrality and simulation of capillary non-perfusion.
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.
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.
Retinal capillary blood flow speeds quantification may provide biomarkers for retinal diseases. While OCTA visualizes the retinal vasculature, it provides limited information about the blood flow speeds. We present an OCTA-based method for measuring quantitative surrogate markers for blood flow speeds in retinal capillaries using a temporal autocorrelation decay model, by acquiring multiple OCT B-scan repeats and compiling OCTA measurements both spatially and temporally. A 600 kHz swept light source enabled short and multiple interscan times with fine A-scan spacing. We show blood flow speed differences among retinal vascular plexuses in healthy eyes and alterations in eyes with diabetic retinopathy.
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.
To non-invasively assess the impact of antibiotic therapy on otitis media (OM), a handheld OCT system was developed to longitudinally monitor in vivo middle ear conditions of OM-induced chinchilla models. The formation of middle ear effusions (MEEs) and biofilm were examined over the course of the infection. 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 antibiotics (ceftriaxone). Quantitative parameters, such as TM thickness and effusion and biofilm scattering/texture, were correlated with histology and fluorescence in situ hybridization (FISH) at the end time point.
Significance: Optical coherence tomography (OCT) offers high spatial resolution and contrast for imaging intraoral structures, yet few studies have investigated its clinical feasibility for dental plaque and gingiva imaging in vivo. Furthermore, the accessibility is often limited to anterior teeth due to bulky imaging systems and probes.
Aim: A custom-designed, handheld probe-based, spectral-domain OCT system with an interchangeable attachment was developed to assess dental plaque and gingival health in a clinical setting.
Approach: Healthy volunteers and subjects with gingivitis and sufficient plaque were recruited. The handheld OCT system was operated by trained dental hygienists to acquire images of dental plaque and gingiva at various locations and after one-week use of oral hygiene products.
Results: The handheld OCT can access premolars, first molars, and lingual sides of teeth to visualize the plaque distribution. OCT intensity-based texture analysis revealed lower intensity from selected sites in subjects with gingivitis. The distribution of the dental plaque after one-week use of the oral hygiene products was compared, showing the capability of OCT as a longitudinal tracking tool.
Conclusions: OCT has a strong potential to display and assess dental plaque and gingiva in a clinical setting. Meanwhile, technological challenges remain to perform systematic longitudinal tracking and comparative analyses.
The current standard for antibiotic susceptibility testing (AST) is based on measuring bacterial growth after 10-24 hours of proliferation. Considering that many life-threatening conditions of infection exist, rapid AST techniques are urgently needed. We developed a rapid AST method based on two-photon fluorescence and coherent anti-Stokes Raman scattering microscopy which can detect antibiotic responses of bacteria within one hour. We used Pseudomonas aeruginosa as a representative pathogen model, and found that antibiotic treatment greatly reduces nicotinamide adenine dinucleotide (phosphate) levels in the bacteria. This enables rapid determination of bacterial susceptibility at the single cell level.
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.
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 have developed a cellular resolution imaging modality, Gabor-Domain Optical Coherence Microscopy, which combines the high lateral resolution of confocal microscopy with the high sectioning capability of optical coherence tomography to image deep layers in tissues with high-contrast and volumetric resolution of 2 μm. A novelty of the custom microscope is the biomimetics that incorporates a liquid lens, as in whales’s eyes, for robust and rapid acquisition of volumetric imaging of deep layers in tissue down to 2 mm, thus overcoming the tradeoff between lateral resolution and depth of focus. The system incorporates a handheld scanning optical imaging head and fits on a movable cart that offers the flexibility in different biomedical applications and clinical settings, including ophthalmology. In the later, the microscope has successfully revealed micro-structures within the cornea and in particular the endothelial cells microenvironment, an important step in understanding the mechanisms of Fuchs’ dystrophy, a leading cause of the loss of corneal transparency. Also, the system was able to provide high definition of the edge of soft contact lenses, which is important for the fitting of the lens and the comfort of the patient. Overall, the imaging modality provides the opportunity to observe the three-dimensional features of different structures with micrometer resolution, which opens a wide range of future applications.
We study experimentally the scanning functions of galvanometer-based scanners (GSs) in order to optimize them for biomedical imaging in general, and for Optical Coherence Tomography (OCT) in particular. The main scanning parameters of the scanning process are taken into account: theoretical duty cycle (of the input signal of the GS), scan frequency (fs), and scan amplitude (θm). Triangular to sawtooth scanning regimes are thus considered. We demonstrate that when increasing the scan frequency and amplitude, the scanning function (i.e., the angular position of the galvomirror) is not able to follow anymore the input signal. Furthermore, as the theoretical duty cycle is increased, the result is unexpected: the effective duty cycle actually decreases – for high fs and θm. A saturation of the device therefore occurs. The practical limits of this phenomenon are discussed. GS users are thus provided with a multi-parameter analysis that allows them for optimizing their scanning regimes and to avoid pushing the devices to their limit – when that actually results in decreasing the quality of the images obtained, by example in OCT. Gabor Domain Optical Coherence Microscopy (GD-OCM) images are made to show effects of this phenomenon.
Gabor-domain optical coherence microscopy (GD-OCM) is a volumetric high-resolution technique capable of acquiring three-dimensional (3-D) skin images with histological resolution. Real-time image processing is needed to enable GD-OCM imaging in a clinical setting. We present a parallelized and scalable multi-graphics processing unit (GPU) computing framework for real-time GD-OCM image processing. A parallelized control mechanism was developed to individually assign computation tasks to each of the GPUs. For each GPU, the optimal number of amplitude-scans (A-scans) to be processed in parallel was selected to maximize GPU memory usage and core throughput. We investigated five computing architectures for computational speed-up in processing 1000×1000 A-scans. The proposed parallelized multi-GPU computing framework enables processing at a computational speed faster than the GD-OCM image acquisition, thereby facilitating high-speed GD-OCM imaging in a clinical setting. Using two parallelized GPUs, the image processing of a 1×1×0.6 mm 3 skin sample was performed in about 13 s, and the performance was benchmarked at 6.5 s with four GPUs. This work thus demonstrates that 3-D GD-OCM data may be displayed in real-time to the examiner using parallelized GPU processing.
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