Analysis of the Porphyrin Peak Shift and Fluorescence Lifetime in Gliomas with Different Tumor Grades, Intratumoral Regions, and Visible Fluorescence Status.

5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence shows high sensitivity in detecting the tumor core of high-grade gliomas (HGG) but poor sensitivity for tissue of low-grade gliomas (LGG) and the margins of HGG. The characteristic emission peak for PpIX is known to be located at 635 nm. Recently, a second emission peak was described at 620 nm wavelength in LGG and the tumor infiltration zone of HGG.

The impact of print orientation and graphene nanoplatelets on biaxial flexural strength and cytotoxicity of a 3D printable resin for occlusal splints.

Objectives: 3D printing found its way into various medical applications and could be particularly beneficial for dentistry. Currently, materials for 3D printing of occlusal splints lack mechanical strength compared to polymethyl methacrylate (PMMA) used for standard milling of occlusal splints. It is known that print orientation and graphene nanoplatelets (GNP) can increase biaxial strength in a variety of materials.

Flavin fluorescence lifetime and autofluorescence optical redox ratio for improved visualization and classification of brain tumors.

Purpose: Modern techniques for improved tumor visualization have the aim to maximize the extent of resection during brain tumor surgery and thus improve patient prognosis. Optical imaging of autofluorescence is a powerful and non-invasive tool to monitor metabolic changes and transformation in brain tumors. Cellular redox ratios can be retrieved from fluorescence emitted by the coenzymes reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD).

Diagnosis of Pituitary Adenoma Biopsies by Ultrahigh Resolution Optical Coherence Tomography Using Neuronal Networks.

Objective: Despite advancements of intraoperative visualization, the difficulty to visually distinguish adenoma from adjacent pituitary gland due to textural similarities may lead to incomplete adenoma resection or impairment of pituitary function. The aim of this study was to investigate optical coherence tomography (OCT) imaging in combination with a convolutional neural network (CNN) for objectively identify pituitary adenoma tissue in an setting.

Methods: A prospective study was conducted to train and test a CNN algorithm to identify pituitary adenoma tissue in OCT images of adenoma and adjacent pituitary gland samples.

Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography.

Significance: After three decades, more than 75,000 publications, tens of companies being involved in its commercialization, and a global market perspective of about USD 1.5 billion in 2023, optical coherence tomography (OCT) has become one of the fastest successfully translated imaging techniques with substantial clinical and economic impacts and acceptance.

Aim: Our perspective focuses on disruptive forward-looking innovations and key technologies to further boost OCT performance and therefore enable significantly enhanced medical diagnosis.

Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery.

Maximal safe resection is a key strategy for improving patient prognosis in the management of brain tumors. Intraoperative fluorescence guidance has emerged as a standard in the surgery of high-grade gliomas. The administration of 5-aminolevulinic acid prior to surgery induces tumor-specific accumulation of protoporphyrin IX, which emits red fluorescence under blue-light illumination.

Toward Quantitative Label-Free Tracking of Lipid Distribution in a Zebrafish Cancer Model.

Cancer cells often adapt their lipid metabolism to accommodate the increased fatty acid demand for membrane biogenesis and energy production. Upregulation of fatty acid uptake from the environment of cancer cells has also been reported as an alternative mechanism. To investigate the role of lipids in tumor onset and progression and to identify potential diagnostic biomarkers, lipids are ideally imaged directly within the intact tumor tissue in a label-free way.

Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging.

Pituitary adenomas count among the most common intracranial tumors. During pituitary oncogenesis structural, textural, metabolic and molecular changes occur which can be revealed with our integrated ultrahigh-resolution multimodal imaging approach including optical coherence tomography (OCT), multiphoton microscopy (MPM) and line scan Raman microspectroscopy (LSRM) on an unprecedented cellular level in a label-free manner. We investigated 5 pituitary gland and 25 adenoma biopsies, including lactotroph, null cell, gonadotroph, somatotroph and mammosomatotroph as well as corticotroph.

Towards ultrahigh resolution OCT based endoscopical pituitary gland and adenoma screening: a performance parameter evaluation.

Ultrahigh resolution optical coherence tomography (UHR-OCT) for differentiating pituitary gland versus adenoma tissue has been investigated for the first time, indicating more than 80% accuracy. For biomarker identification, OCT images of paraffin embedded tissue are correlated to histopathological slices. The identified biomarkers are verified on fresh biopsies.

Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors.

Maximal safe tumor resection remains the key prognostic factor for improved prognosis in brain tumor patients. Despite 5-aminolevulinic acid-based fluorescence guidance the neurosurgeon is, however, not able to visualize most low-grade gliomas (LGG) and infiltration zone of high-grade gliomas (HGG). To overcome the need for a more sensitive visualization, we investigated the potential of macroscopic, wide-field fluorescence lifetime imaging of nicotinamide adenine dinucleotide (NADH) and protoporphyrin IX (PPIX) in selected human brain tumors.

Functional optical coherence tomography and photoacoustic microscopy imaging for zebrafish larvae.

We present a dual modality functional optical coherence tomography and photoacoustic microscopy (OCT-PAM) system. The photoacoustic modality employs an akinetic optical sensor with a large imaging window. This imaging window enables direct reflection mode operation, and a seamless integration of optical coherence tomography (OCT) as a second imaging modality.

Towards real-time wide-field fluorescence lifetime imaging of 5-ALA labeled brain tumors with multi-tap CMOS cameras.

Fluorescence guided neurosurgery based on 5-aminolevulinic acid (5-ALA) has significantly increased maximal safe resections. Fluorescence lifetime imaging (FLIM) of 5-ALA could further boost this development by its increased sensitivity. However, neurosurgeons require real-time visual feedback which was so far limited in dual-tap CMOS camera based FLIM.

Surgical microscope with integrated fluorescence lifetime imaging for 5-aminolevulinic acid fluorescence-guided neurosurgery.

Significance: 5-Aminolevulinic acid (5-ALA)-based fluorescence guidance in conventional neurosurgical microscopes is limited to strongly fluorescent tumor tissue. Therefore, more sensitive, intrasurgical 5-ALA fluorescence visualization is needed.

Aim: Macroscopic fluorescence lifetime imaging (FLIM) was performed ex vivo on 5-ALA-labeled human glioma tissue through a surgical microscope to evaluate its feasibility and to compare it to fluorescence intensity imaging.

Line Scan Raman Microspectroscopy for Label-Free Diagnosis of Human Pituitary Biopsies.

Pituitary adenomas are neoplasia of the anterior pituitary gland and can be subdivided into hormone-producing tumors (lactotroph, corticotroph, gonadotroph, somatotroph, thyreotroph or plurihormonal) and hormone-inactive tumors (silent or null cell adenomas) based on their hormonal status. We therefore developed a line scan Raman microspectroscopy (LSRM) system to detect, discriminate and hyperspectrally visualize pituitary gland from pituitary adenomas based on molecular differences. By applying principal component analysis followed by a k-nearest neighbor algorithm, specific hormone states were identified and a clear discrimination between pituitary gland and various adenoma subtypes was achieved.

Automatic assessment of tear film and tear meniscus parameters in healthy subjects using ultrahigh-resolution optical coherence tomography.

Many different parameters exist for the investigation of tear film dynamics. We present a new tear meniscus segmentation algorithm which automatically extracts tear meniscus area (TMA), height (TMH), depth (TMD) and radius (TMR) from UHR-OCT measurements and apply it to a data set including repeated measurements from ten healthy subjects. Mean values and standard deviations are 0.

Ultrashort pulse Kagome hollow-core photonic crystal fiber delivery for nonlinear optical imaging.

We report ultrashort pulse delivery through a hypocycloid-core inhibited-coupling Kagome hollow-core photonic crystal fiber (HC-PCF). Undistorted 10 fs and 6.6 nJ pulses were launched through 1 m long fiber without fiber dispersion pre-compensation and 80% efficiency.

Depth resolved label-free multimodal optical imaging platform to study morpho-molecular composition of tissue.

Multimodal imaging platforms offer a vast array of tissue information in a single image acquisition by combining complementary imaging techniques. By merging different systems, better tissue characterization can be achieved than is possible by the constituent imaging modalities alone. The combination of optical coherence tomography (OCT) with non-linear optical imaging (NLOI) techniques such as two-photon excited fluorescence (TPEF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) provides access to detailed information of tissue structure and molecular composition in a fast, label-free and non-invasive manner.

Ultrahigh-resolution anterior segment optical coherence tomography for analysis of corneal microarchitecture during wound healing.

Purpose: To employ ultrahigh-resolution (UHR) optical coherence tomography (OCT) for investigation of the early wound healing process in corneal epithelium.

Methods: A custom-built UHR-OCT system assessed epithelial healing in human keratoconic cornea after epi-off crosslinking (CXL) procedure and a wound healing model in rabbits with iatrogenic corneal injury. 3D OCT data sets enhanced obtaining epithelial thickness maps and evaluation of reepithelization stage.

Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence-guided neurosurgery: An ex vivo feasibility study.

Achieving a maximal safe extent of resection during brain tumor surgery is the goal for improved patient prognosis. Fluorescence-guided neurosurgery using 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX has thereby become a valuable tool enabling a high frequency of complete resections and a prolonged progression-free survival in glioblastoma patients. We present a widefield fluorescence lifetime imaging device with 250 mm working distance, working under similar conditions such as surgical microscopes based on a time-of-flight dual tap CMOS camera.

Integrated single- and two-photon light sheet microscopy using accelerating beams.

We demonstrate the first light sheet microscope using propagation invariant, accelerating Airy beams that operates both in single- and two-photon modes. The use of the Airy beam permits us to develop an ultra compact, high resolution light sheet system without beam scanning. In two-photon mode, an increase in the field of view over the use of a standard Gaussian beam by a factor of six is demonstrated.

A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome.

Purpose: This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES).

Methods: This was a controlled, randomized, double-blind clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21 patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye and placebo (normal saline solution) in the contralateral eye.

In vivo tear film thickness measurement and tear film dynamics visualization using spectral domain optical coherence tomography.

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure tear film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator.

Single-pulse CARS based multimodal nonlinear optical microscope for bioimaging.

Noninvasive label-free imaging of biological systems raises demand not only for high-speed three-dimensional prescreening of morphology over a wide-field of view but also it seeks to extract the microscopic functional and molecular details within. Capitalizing on the unique advantages brought out by different nonlinear optical effects, a multimodal nonlinear optical microscope can be a powerful tool for bioimaging. Bringing together the intensity-dependent contrast mechanisms via second harmonic generation, third harmonic generation and four-wave mixing for structural-sensitive imaging, and single-beam/single-pulse coherent anti-Stokes Raman scattering technique for chemical sensitive imaging in the finger-print region, we have developed a simple and nearly alignment-free multimodal nonlinear optical microscope that is based on a single wide-band Ti:Sapphire femtosecond pulse laser source.