Optical coherence tomography velocimetry based on decorrelation estimation of phasor pair ratios (DEPPAIR).

Quantitative velocity estimations in optical coherence tomography requires the estimation of the axial and lateral flow components. Optical coherence tomography measures the depth resolved complex field reflected from a sample. While the axial velocity component can be determined from the Doppler shift or phase shift between a pair of consecutive measurements at the same location, the estimation of the lateral component for applications is still challenging.

Optical coherence tomography (OCT) to image active and inactive retinoblastomas as well as retinomas.

Purpose: To illustrate Optical Coherence Tomography (OCT) images of active and inactive retinoblastoma (Rb) tumours.

Methods: Current observational study included patients diagnosed with retinoblastoma and retinoma who were presented at Amsterdam UMC and Jules-Gonin Eye Hospital, between November 2010 and October 2017. Patients aged between 0 and 4 years were imaged under general anaesthesia with handheld OCT in supine position.

Phase-based OCT angiography in diagnostic imaging of pediatric retinoblastoma patients: abnormal blood vessels in post-treatment regression patterns.

Phase-based OCT angiography of retinoblastoma regression patterns with a novel handheld 1050 nm clinical imaging system is demonstrated for the first time in children between 0 and 4 years old under general anesthesia. Angiography is mapped at OCT resolution by flow detection at every pixel with en-face projection from the volume between nerve fiber layer and retinal pigment epithelium. We show a striking difference between blood vasculature of healthy retina, and retinoblastoma regression patterns after chemotherapy, as well as varying complexity of abnormal vasculature in regression patterns types 2, 3, and 4.

3D texture analysis for classification of second harmonic generation images of human ovarian cancer.

Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class.

Texture analysis applied to second harmonic generation image data for ovarian cancer classification.

Remodeling of the extracellular matrix has been implicated in ovarian cancer. To quantitate the remodeling, we implement a form of texture analysis to delineate the collagen fibrillar morphology observed in second harmonic generation microscopy images of human normal and high grade malignant ovarian tissues. In the learning stage, a dictionary of “textons”—frequently occurring texture features that are identified by measuring the image response to a filter bank of various shapes, sizes, and orientations—is created.

Estimating the risk of squamous cell cancer induction in skin following nonlinear optical imaging.

High power femto-second (fs) laser pulses used for in-vivo nonlinear optical (NLO) imaging can form cyclobutane pyrimidine dimers (CPD) in DNA, which may lead to carcinogenesis via subsequent mutations. Since UV radiation from routine sun exposure is the primary source of CPD lesions, we evaluated the risk of CPD-related squamous cell carcinoma (SCC) in human skin due to NLO imaging relative to that from sun exposure. We developed a unique cancer risk model expanding previously published estimation of risk from exposure to continuous wave (CW) laser.

Carcinogenic damage to deoxyribonucleic acid is induced by near-infrared laser pulses in multiphoton microscopy via combination of two- and three-photon absorption.

Nonlinear optical imaging modalities (multiphoton excited fluorescence, second and third harmonic generation) applied in vivo are increasingly promising for clinical diagnostics and the monitoring of cancer and other disorders, as they can probe tissue with high diffraction-limited resolution at near-infrared (IR) wavelengths. However, high peak intensity of femtosecond laser pulses required for two-photon processes causes formation of cyclobutane-pyrimidine-dimers (CPDs) in cellular deoxyribonucleic acid (DNA) similar to damage from exposure to solar ultraviolet (UV) light. Inaccurate repair of subsequent mutations increases the risk of carcinogenesis.

Structural changes in mixed Col I/Col V collagen gels probed by SHG microscopy: implications for probing stromal alterations in human breast cancer.

Second Harmonic Generation (SHG) microscopy has been previously used to describe the morphology of collagen in the extracellular matrix (ECM) in different stages of invasion in breast cancer. Here this concept is extended by using SHG to provide quantitative discrimination of self-assembled collagen gels, consisting of mixtures of type I (Col I) and type V (Col V) isoforms which serve as models of changes in the ECM during invasion in vivo. To investigate if SHG is sensitive to changes due to Col V incorporation into Col I fibrils, gels were prepared with 0-20% Col V with the balance consisting of Col I.

Alterations of the extracellular matrix in ovarian cancer studied by Second Harmonic Generation imaging microscopy.

Background: Remodeling of the extracellular matrix (ECM) has been implicated in ovarian cancer, and we hypothesize that these alterations may provide a better optical marker of early disease than currently available imaging/screening methods and that understanding their physical manifestations will provide insight into invasion.

Methods: For this investigation we use Second Harmonic Generation (SHG) imaging microcopy to study changes in the structure of the ovarian ECM in human normal and malignant ex vivo biopsies. This method directly visualizes the type I collagen in the ECM and provides quantitative metrics of the fibrillar assembly.

Retention of polarization signatures in SHG microscopy of scattering tissues through optical clearing.

Polarization responses in Second Harmonic Generation (SHG) imaging microscopy are a valuable method to quantify aspects of tissue structure, and may be a means to differentiate normal and diseased tissues. Due to multiple scattering, the polarization data is lost in turbid tissues. Here we investigate if this information can be retained through the use of optical clearing which greatly reduces the scattering coefficient and increases the corresponding mean free path.

Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon.

We have investigated the mechanisms and capabilities of optical clearing in conjunction with second harmonic generation (SHG) imaging in tendon and striated muscle. Our approach combines three-dimensional (3-D) SHG imaging of the axial attenuation and directional response with Monte Carlo simulation (based on measured bulk optical properties) of the creation intensity and propagation through the tissues. Through these experiments and simulations, we show that reduction of the primary filter following glycerol treatment dominates the axial attenuation response in both muscle and tendon.

Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation.

We report the integrated use of 3D second harmonic generation (SHG) imaging microscopy and Monte Carlo simulation as a combined metric to quantifiably differentiate normal and diseased tissues based on the physical properties of the respective extracellular matrix. To achieve this, we have identified a set of parameters comprised of the SHG creation attributes and the bulk optical parameters, which are used collectively via comparative analysis. Monte Carlo simulations of the SHG axial directional and attenuation responses allow their decomposition into the underlying factors that are not readily obtainable through experimental techniques.

Second harmonic generation imaging microscopy studies of osteogenesis imperfecta.

We have used quantitative second harmonic generation (SHG) imaging microscopy to investigate the collagen matrix organization in the oim mouse model for human osteogenesis imperfecta (OI). OI is a heritable disease in which the type I collagen fibrils are either abnormally organized or small, resulting in a clinical presentation of recurrent bone fractures and other pathologies related to collagen-comprised tissues. Exploiting the exquisite sensitivity of SHG to supramolecular assembly, we investigated whether this approach can be utilized to differentiate normal and oim tissues.

Coherent and incoherent SHG in fibrillar cellulose matrices.

Second Harmonic Generation (SHG) microscopy probes the organization of tissue or material structure through morphological and polarization analyses. In terms of diagnostic or analytical potential, it is important to understand the coherent and incoherent aspects of the emission in highly scattering environments. It is also of fundamental importance whether the SHG polarization signatures are retained in such turbid media.