Multiphoton Microscopy Assessment of Healing From Tendon Laceration and Microthermal Coagula in a Rat Model.

Objectives: To study the healing response of rat Achilles tendon when lacerated or treated with intense therapeutic ultrasound (ITU) via utilization of multiphoton microscopy (MPM) imaging and histology.

Materials And Methods: The right Achilles tendon of each Sprague Dawley rat within a cohort was partially lacerated. 1 to 2 days post-surgery, each rat received ITU treatment of the Achilles tendon on either the right or left leg.

Targeted multispectral filter array design for the optimization of endoscopic cancer detection in the gastrointestinal tract.

Significance: Color differences between healthy and diseased tissue in the gastrointestinal (GI) tract are detected visually by clinicians during white light endoscopy; however, the earliest signs of cancer are often just a slightly different shade of pink compared to healthy tissue making it hard to detect. Improving contrast in endoscopy is important for early detection of disease in the GI tract during routine screening and surveillance.

Aim: We aim to target alternative colors for imaging to improve contrast using custom multispectral filter arrays (MSFAs) that could be deployed in an endoscopic "chip-on-tip" configuration.

Combined flat-field and frequency filter approach to correcting artifacts of multichannel two-photon microscopy.

Significance: Multiphoton microscopy (MPM) is a useful biomedical imaging tool for its ability to probe labeled and unlabeled depth-resolved tissue biomarkers at high resolution. Automated MPM tile scanning allows for whole-slide image acquisition but can suffer from tile-stitching artifacts that prevent accurate quantitative data analysis.

Aim: We have investigated postprocessing artifact correction methods using ImageJ macros and custom Python code.

Evaluating backscattering polarized light imaging microstructural mapping capabilities through neural tissue and analogous phantom imaging.

Significance: Knowledge of fiber microstructure and orientation in the brain is critical for many applications. Polarized light imaging (PLI) has been shown to have potential for better understanding neural fiber microstructure and directionality due to the anisotropy in myelin sheaths surrounding nerve fibers of the brain. Continuing to advance backscattering based PLI systems could provide a valuable avenue for neural imaging.

Wide field-of-view fluorescence imaging for organ-level lineage tracing of rare intestinal stem cell populations.

Significance: Lineage tracing using fluorescent reporters is a common tool for monitoring the expression of genes and transcription factors in stem cell populations and their progeny. The zinc-binding protein 89 (ZBP-89/Zfp148 mouse gene) is a transcription factor that plays a role in gastrointestinal (GI) stem cell maintenance and cellular differentiation and has been linked to the progression of colon cancer. While lineage tracing is a useful tool, it is commonly performed with high-magnification microscopy on a small field of view within tissue sections, thereby limiting the ability to resolve reporter expression at the organ level.

Design, fabrication, and preclinical testing of a miniaturized, multispectral, chip-on-tip, imaging probe for intraluminal fluorescence imaging of the gastrointestinal tract.

Gastrointestinal cancers continue to account for a disproportionately large percentage of annual cancer deaths in the US. Advancements in miniature imaging technology combined with a need for precise and thorough tumor detection in gastrointestinal cancer screenings fuel the demand for new, small-scale, and low-cost methods of localization and margin identification with improved accuracy. Here, we report the development of a miniaturized, chip-on-tip, multispectral, fluorescence imaging probe designed to port through a gastroscope working channel with the aim of detecting cancerous lesions in point-of-care endoscopy of the gastrointestinal lumen.

Combined multiphoton microscopy and somatostatin receptor type 2 imaging of pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs) are a rare but increasingly more prevalent cancer with heterogeneous clinical and pathological presentation. Surgery is the preferred treatment for all hormone-expressing PNETs and any PNET greater than 2 cm, but difficulties arise when tumors are multifocal, metastatic, or small in size due to lack of effective surgical localization. Existing techniques such as intraoperative ultrasound provide poor contrast and resolution, resulting in low sensitivity for such tumors.

Multispectral imaging of nailfold capillaries using light-emitting diode illumination.

Significance: The capillaries are the smallest blood vessels in the body, typically imaged using video capillaroscopy to aid diagnosis of connective tissue diseases, such as systemic sclerosis. Video capillaroscopy allows visualization of morphological changes in the nailfold capillaries but does not provide any physiological information about the blood contained within the capillary network. Extracting parameters such as hemoglobin oxygenation could increase sensitivity for diagnosis and measurement of microvascular disease progression.

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy.

Background: Duodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTs is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins.

GFAP-directed Inactivation of Men1 Exploits Glial Cell Plasticity in Favor of Neuroendocrine Reprogramming.

Background & Aims: Efforts to characterize the signaling mechanisms that underlie gastroenteropancreatic neoplasms (GEP-NENs) are precluded by a lack of comprehensive models that recapitulate pathogenesis. Investigation into a potential cell-of-origin for gastrin-secreting NENs revealed a non-cell autonomous role for loss of menin in neuroendocrine cell specification, resulting in an induction of gastrin in enteric glia. Here, we investigated the hypothesis that cell autonomous Men1 inactivation in glial fibrillary acidic protein (GFAP)-expressing cells induced neuroendocrine differentiation and tumorigenesis.

Opti-MSFA: a toolbox for generalized design and optimization of multispectral filter arrays.

Multispectral imaging captures spatial information across a set of discrete spectral channels and is widely utilized across diverse applications such as remote sensing, industrial inspection, and biomedical imaging. Multispectral filter arrays (MSFAs) are filter mosaics integrated atop image sensors that facilitate cost-effective, compact, snapshot multispectral imaging. MSFAs are pre-configured based on application-where filter channels are selected corresponding to targeted absorption spectra-making the design of optimal MSFAs vital for a given application.

Ovarian cancer detection using optical coherence tomography and convolutional neural networks.

Ovarian cancer has the sixth-largest fatality rate in the United States among all cancers. A non-surgical assay capable of detecting ovarian cancer with acceptable sensitivity and specificity has yet to be developed. However, such a discovery would profoundly impact the pace of the treatment and improvement to patients' quality of life.

Robustness to misalignment of low-cost, compact quantitative phase imaging architectures.

Non-interferometric approaches to quantitative phase imaging could enable its application in low-cost, miniaturised settings such as capsule endoscopy. We present two possible architectures and both analyse and mitigate the effect of sensor misalignment on phase imaging performance. This is a crucial step towards determining the feasibility of implementing phase imaging in a capsule device.

Effect of an Added Mass on the Vibration Characteristics for Raster Scanning of a Cantilevered Optical Fiber.

Piezoelectric tube actuators with cantilevered optical fibers have enabled the miniaturization of scanning image acquisition techniques for endoscopic implementation. To achieve raster scanning for such a miniaturized system, the first resonant frequency should be of the order of 10 s of Hz. We explore adding a mass at an intermediate location along the length of the fiber to alter the resonant frequencies of the system.

Pilot Study: Texture Analysis of PET Imaging Demonstrates Changes in F-FDG Uptake of the Brain After Prophylactic Cranial Irradiation.

Prophylactic cranial irradiation (PCI) is used to decrease the probability of developing brain metastases in patients with small cell lung cancer and has been linked to deleterious cognitive effects. Although no well-established imaging markers for these effects exist, previous studies have shown that structural and metabolic changes in the brain can be detected with MRI and PET. This study used an image processing technique called texture analysis to explore whether global changes in brain glucose metabolism could be characterized in PET images.

Use of embedded and patterned dichroic surfaces with reflective optical power to enable multiple optical paths in a micro-objective.

We demonstrate the use of patterned dichroic surfaces with reflective optical power to create multiple optical paths in a single lens system. The application of these surfaces enables a micro-endoscope to accommodate multiple imaging technologies with only one optical system, making the packaging more compact and reliable. The optical paths are spectrally separated using different wavelengths for each path.

Fluorescence and Multiphoton Imaging for Tissue Characterization of a Model of Postmenopausal Ovarian Cancer.

Background And Objectives: To determine the efficacy of targeted fluorescent biomarkers and multiphoton imaging to characterize early changes in ovarian tissue with the onset of cancer.

Study Design/materials And Methods: A transgenic TgMISIIR-TAg mouse was used as an animal model for ovarian cancer. Mice were injected with fluorescent dyes to bind to the folate receptor α, matrix metalloproteinases, and integrins.

Quantification of multiphoton and fluorescence images of reproductive tissues from a mouse ovarian cancer model shows promise for early disease detection.

Ovarian cancer is the deadliest gynecologic cancer due predominantly to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Multiphoton microscopy (MPM) is a relatively new imaging technique sensitive to endogenous fluorophores, which has tremendous potential for clinical diagnosis, though it is limited in its application to the ovaries.

Evaluation of segmentation algorithms for optical coherence tomography images of ovarian tissue.

Ovarian cancer has the lowest survival rate among all gynecologic cancers predominantly due to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Optical coherence tomography (OCT) is an emerging technique that provides depth-resolved, high-resolution images of biological tissue in real-time and demonstrates great potential for imaging of ovarian tissue.

Three-dimensional texture analysis of optical coherence tomography images of ovarian tissue.

Ovarian cancer has the lowest survival rate among all gynecologic cancers due to predominantly late diagnosis. Optical coherence tomography (OCT) has been applied successfully to experimentally image the ovaries in vivo; however, a robust method for analysis is still required to provide quantitative diagnostic information. Recently, texture analysis has proved to be a useful tool for tissue characterization; unfortunately, existing work in the scope of OCT ovarian imaging is limited to only analyzing 2D sub-regions of the image data, discarding information encoded in the full image area, as well as in the depth dimension.

Alignment of sensor arrays in optical instruments using a geometric approach.

Alignment of sensor arrays in optical instruments is critical to maximize the instrument's performance. While many commercial systems use standardized mounting threads for alignment, custom systems require specialized equipment and alignment procedures. These alignment procedures can be time-consuming, dependent on operator experience, and have low repeatability.

Using confidence intervals to evaluate the focus alignment of spectrograph detector arrays.

High-resolution spectrographs extract detailed spectral information of a sample and are frequently used in astronomy, laser-induced breakdown spectroscopy, and Raman spectroscopy. These instruments employ dispersive elements such as prisms and diffraction gratings to spatially separate different wavelengths of light, which are then detected by a charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) detector array. Precise alignment along the optical axis (focus position) of the detector array is critical to maximize the instrumental resolution; however, traditional approaches of scanning the detector through focus lack a quantitative measure of precision, limiting the repeatability and relying on one's experience.

Tolerancing the alignment of large-core optical fibers, fiber bundles and light guides using a Fourier approach.

Optical fiber technology is found in a wide variety of applications to flexibly relay light between two points, enabling information transfer across long distances and allowing access to hard-to-reach areas. Large-core optical fibers and light guides find frequent use in illumination and spectroscopic applications, for example, endoscopy and high-resolution astronomical spectroscopy. Proper alignment is critical for maximizing throughput in optical fiber coupling systems; however, there currently are no formal approaches to tolerancing the alignment of a light-guide coupling system.