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.
Influenced by both the intrinsic viscoelasticity of the tissue constituents and the time-evolved redistribution of fluid within the tissue, the biomechanical response of skin can reflect not only localized pathology but also systemic physiology of an individual. While clinical diagnosis of skin pathologies typically relies on visual inspection and manual palpation, a more objective and quantitative approach for tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that enables in vivo assessment of cross-sectional tissue morphology with micron-scale resolution, which surpasses those of most standard clinical imaging tools, such as ultrasound imaging and magnetic resonance imaging. This pilot study investigates the feasibility of characterizing the biomechanical response of in vivo human skin using OCT. OCT-based quantitative metrics were developed and demonstrated on the human subject data, where a significant difference between deformed and nondeformed skin was revealed. Additionally, the quantified postindentation recovery results revealed differences between aged (adult) and young (infant) skin. These suggest that OCT has the potential to quantitatively assess the mechanically perturbed skin as well as distinguish different physiological conditions of the skin, such as changes with age or disease.
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.
We performed ratiometric analysis of retinal optical coherence tomography images for the first time in multiple sclerosis (MS) patients. The ratiometric analysis identified differences in several retinal layer thickness ratios in the cohort of MS subjects without a history of optic neuritis (ON) compared to healthy control (HC) subjects, and there was no difference in standard retinal nerve fiber layer thickness (RNFLT). The difference in such ratios between HC subjects and those with mild MS-disability, without a difference in RNFLT, further suggests the possibility of using layer ratiometric analysis for detecting early retinal changes in MS. Ratiometric analysis may be useful and potentially more sensitive for detecting disease changes in MS.
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.
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.
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.
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