The unique 3D imaging scale of OCT enables high-resolution tracking of large-size particle over a millimeter-level field of view. However, limited volumetric imaging speed hinders the assessment of fast movement, where a significant sacrifice in spatial sampling or transverse scanning distance is often needed. To address this technical hurdle in the application of studying the transport of preimplantation embryos in the mouse oviduct (fallopian tube) in vivo, we developed a new velocimetry method that relies on the particle streak formed in a single OCT volume containing double B-scans at each B-scan location, providing 3D structure information with particle velocity.

Motile cilia lining the lumen of the Fallopian tube (oviduct) are known to play an essential role in reproduction; however, how their specific roles are not understood. Here, we present a novel dynamic OCT method for imaging of waves propagating along the epithelial surfaces created by the beating cilia (metachronal waves). The method is based on spatiotemporal mapping of the phase of ciliary beat calculated based on intensity fluctuations in OCT images. This method was applied in vivo to visualize and quantify cilia metachronal waves within the mouse fallopian tube in vivo, volumetrically, through the tissue layers.

We demonstrate longitudinal drug response imaging of tumor spheroids by integrating a spheroid cultivation chamber and the dynamic optical coherence tomography (DOCT) system. The cultivation chamber supports the spheroids with 5 % of CO2 and a temperature of 37 0C. In contrast to our previous cross-sectional time-course imaging method, this newly integrated system enabled longitudinal time-course imaging of a single sample, and hence enabled measuring large number of time-points of the same spheroid. It successfully revealed the temporal property of human breast cancer (MCF-7 cell-line) spheroid’s response to paclitaxel (PTX) and doxorubicin (DOX) with high-temporal-resolution.

We present longitudinal functional activity imaging of liver functional zones in the presence of metabolic inhibitor drug with dynamic optical coherence tomography (DOCT). We studied a normal liver and a liver injected with metformin. In the normal liver, we found a correlation between the vascular structures observed in the DOCT and OCT projections. Over time, these vascular structures gradually decreased in the DOCT, while similar structures appeared in the OCT at a later time point. In the metformin-injected liver, we observed hexagonal liver lobule structures in the OCT. At late time point, several vessel-like structures with increased scattering appeared in the OCT, which were not initially present in the DOCT.

It is well known that many cancers have their first manifestations at the nanoscale. There is a clinical need for technologies which are sensitive to sub-surface tissue structural changes at the nanoscale, since the most troubling developments in cells and the extracellular matrix occur at this level. In the present study we investigate the usefulness of the nsOCT technique in the assessment and discrimination between healthy skin and cancer margin tissue by comparing information obtained from OCT imaging with high-resolution confocal microscopy image and the gold standard of histological examination of resected surgical specimens.

Prostate cancer is the most prevalent cancer among Canadian men and is often treated with radiation therapy. Historically, cancer has been studied using 2D cell culture methods, but recently 3D cell culture methods like tumor spheroids have been become popular to better replicate the physiological environment of the body. We developed ultrahigh resolution line-field OCT (LF-OCT) technology and a dynamic OCT (dOCT) method to image tumor spheroids and identify areas of necrosis, for comparison with computer simulation. The LF-OCT system has sufficient spatial resolution to identify individual cells and capture the cellular level of activity while the dOCT algorithm can resolve the dynamic activity accurately. The study will be extended to investigate the spatial and temporal development of necrosis in PC3 prostate tumor spheroids after irradiation. These results will be used to inform and extend the model to an in vivo environment.

Visualization of nanoscale structural changes in biological samples for early detection of different pathologies poses a significant challenge to both researchers and healthcare professionals. The spectral encoding of spatial frequency (SESF) approach permits label free visualization of the sub-wavelength structure in 2D imaging with super-resolution. We present an adaptation of the SESF approach for depth resolved visualization of the sub-wavelength structure with nano-sensitivity to structural alterations using optical coherence tomography (OCT). We will describe the principles of the SESF approach, adaptation to OCT, and demonstrate different applications which show advantages of these novel techniques in comparison with existing optical imaging.

Altered retinal neurovascular coupling may contribute to the development and progression of diabetic retinopathy (DR) but remains highly challenging to measure. Here, we present a novel modality of functional OCT angiography (fOCTA) that allows a 3D imaging of retinal functional hyperemia across the entire vascular tree with single-capillary resolution. The high-resolution fOCTA revealed that the retinal capillaries exhibited apparent hyperemic response in normal mice and significant functional hyperemia loss at an early stage of DR and visible restoration after aminoguanidine treatment. The proposed retinal fOCTA would provide new insights into the pathophysiology, screening, and treatment of early DR.

We present mesoscale imaging of nanoparticle-labeled cells in 3D culture with photothermal optical coherence tomography (PT-OCT). Cells labeled with gold nanorods (AuNRs) are encapsulated in agarose-based gel for PT-OCT with 660-nm laser. We show a binary PT contrast for single cell detection without causing cell death. We also demonstrate 3D mapping of AuNR-labeled cells within optically scattering media by imaging through a layer of polystyrene beads mimicking highly scattering tissue and through a layer of cells without AuNRs. This method has an imaging scale that complements the other major cell imaging techniques for studying live cells in 3D culture.

Cellular traction forces are crucial in cell functions like migration, communication, mechanotransduction, adhesion, and shape regulation. Traction force microscopy uses the displacements of fluorescent beads embedded on the surface of a soft substrate of known mechanical properties to quantify the forces induced by cell contraction. However, current methods based on image correlation are time-consuming and suffer from poor repeatability. Here, we propose to use the Demons algorithm as a faster and more accurate approach to measure the displacement of beads. We demonstrate using simulations of mechanically constrained gels confirm that this approach outperforms the gold standard, as it is ten times faster, more robust to noise and defocusing, and capable of producing physiologically relevant displacement fields. Live cell traction force experiments validate the reproducibility of the technique.

Diffuse correlation spectroscopy (DCS) is an optical technique that allows for non-invasive measurements of tissue perfusion, and is often used for neuromonitoring applications. However, a major challenge of DCS is low SNR for deep tissue measurements. Recent works have demonstrated the potential for SPAD arrays to provide significant SNR increases by averaging autocorrelation signals from individual speckles. Such methods may still be suboptimal for efficient signal extraction, as the individual signals may each be low fidelity. In this work, we explore alternative methods of integrating parallelized DCS signals in low photon regimes for accurate blood flow estimation.

Diffuse correlation spectroscopy (DCS) is an optical technique which is used to estimate blood flow in tissue through the analysis of the temporal fluctuations in light intensity. Recently, the development of interferometric techniques (iDCS/iDWS), have allowed for drastic improvement in measurement SNR. In this work, we build upon the iDCS technique by combining it with another advanced DCS modality, time-domain DCS (TD-DCS). This combination allows for the application of pathlength specific coherent gain, which has the potential to further improve the performance of DCS in the non-invasive measurement of deep tissue blood flow.

Diffuse correlation spectroscopy is a widely used optical technique for recovery of blood flow. Its applications have included monitoring of ischemia, blood flow in tumors, and cerebral blood flow. Recently, several variants on this technology have been developed with potential to enhance sensitivity to deep tissues, increase signal-to-noise ratio, and lower costs. Here, we employ diffuse correlation spectroscopy, speckle contrast optical spectroscopy, and interferometric diffusing wave spectroscopy concurrently to measure in vivo and in vitro flow. The results elucidate the advantages and disadvantages of each modality and will aid researchers in selecting a blood flow monitoring method for specific applications.

Optical methods can provide noninvasive approach for continuous cerebral blood flow (CBF) monitoring in humans in vivo. Diffuse correlation spectroscopy (DCS) is an established modality for qualitative CBF monitoring. DCS decodes the CBF from an analysis of the temporal correlations of the light scattered by the tissue. This, however, requires ultra-fast, generating vast amount of data to be processed. Instead of rapidly sensing temporal correlations, we can decode sample dynamics by quantifying speckle contrast, which is inversely proportional to the blood flow. Here, we analyze such an approach in the continuous-wave parallel interferometric near-infrared spectroscopy (CW-πNIRS)

Accurate assessment of cerebral microvascular flow is crucial for understanding brain functioning and neurovascular diseases. Dynamic Light Scattering Optical Coherence Tomography (DLS-OCT) has been used to obtain blood velocity measurements in a large number of microvascular segments, including arterioles, capillaries, and venules in anesthetized mice. However, anesthesia induces large changes in the microvascular blood flow. Imaging awake animals by DLS-OCT is preferable, but very challenging due to motion artifacts. Here, we present the first DLS-OCT measurements of cortical microvascular blood flow in awake mice, made possible by an innovative algorithm based on Vertical Displacement at Inflection (IVD) in velocity distribution.

Oscillometric techniques are the established standard for non-invasively determining blood pressure. Several algorithms exist for translating oscillometric cardiac waveforms to blood pressure values. These algorithms utilize features of the oscillometric blood pressure waveform to extract systolic and diastolic pressures. Though validated empirically, these features remain contested and are somewhat detached from physiology. The accuracy of current algorithms therefore varies on a patient-to-patient basis and especially declines in non-normotensive patients. We propose an alternative technique based on the assertion that, during cuff deflation following arm occlusion, reperfusion begins when cuff pressure equals systolic pressure. This reperfusion process manifests in relative oxyhemoglobin changes (∆HbO). We measure these changes via near-infrared spectroscopy (NIRS) and show that they produce a more accurate estimate of systolic pressure than existing oscillometric methods.

This paper highlights the importance of objective evaluation of perspiration and the limitations of current methods in studying sweat gland function and assessing antiperspirant efficacy. To overcome these limitations, the authors introduce infrared thermography (IRT) as a non-contact imaging modality. They demonstrate the feasibility of IRT through two approaches: high-resolution thermal imaging of sweat pores and pore activation, and quantitative mapping of sweat retention in clothing. IRT offers a non-invasive and versatile tool for studying the effectiveness of antiperspirants and understanding sweat pore behavior. It has the potential to enhance our knowledge of antiperspirant performance and aid in the development of improved formulations. With its detailed insights into sweat pore dynamics, IRT can advance research in the field of human perspiration and serve as a valuable tool for evaluating antiperspirant products.

The Siegert relationship is an important tool in biomedical optics to infer statistics of temporal field fluctuations from observations of intensity fluctuations. The Siegert relationship derivation assumes dynamic Gaussian fields with zero mean. To accommodate a non-ergodic or static field, a modification of the Siegert relationship is often invoked. We show that conventional forms of the modified Siegert relationship, which assume that the coherence factor of dynamic fields also determines mutual coherence between dynamic and static fields, are incorrect in general. We propose a more general form of the modified Siegert relationship and validate it experimentally.

The goal of this study was to investigate how nano-channels created by laser irradiation can affect the diffusion properties of cartilage. Nano-channels were created using a 400 µm fiber optic and a 1550 nm laser. Optical polarization images confirmed the creation of nano-channels. Samples were placed in a homemade diffusion chamber, containing CuSO4 solution and distilled water in the donor and recipient chambers, respectively. T1 weighted MR images were taken over several time points and processed to analyze the rate of diffusion through each sample. Peak diffusion occurred at 24 hours for treated samples and 48 hours for native samples. At 24-hours, diffusion rate was approximately 50% higher in treated samples. At 72-hours, diffusion rate was 9% higher in treated samples. Our results highlight that laser treatment could improve treatment of diseases and injuries of cartilage. Optical confocal imaging is underway to investigate the microscopic morphology of the treated samples.

The progress in laser-based technologies helps to implement compact and reliable semiconductor light sources emitting in near-infrared (NIR) spectrum range significantly gaining PBM effect deeper in the brain. Here we focus on applications of the NIR laser of 1267 nm, proving its efficiency in transforming 3O2 to its active form of 1O2 in anoxygenic organic solution. Later it was demonstrated that a shift in redox potential triggered by NIR laser in different cell types including primary neurons and astrocytes where activation of ATP synthesis was detected. And finally a 4-week course of photosenitiser-free NIR laser treatment (LT), non-invasively suppresses the glioblastoma (GBM) growth in rats and significantly increases animal survival rate. The animals with GBM LT suppressed the GBM progression through activation of apoptosis of the GBM cells and inhibition of their proliferation. Therefore, the PS-free-LT may become a promising alternative therapeutic approach in developing a breakthrough technology for the non-invasive treatment of GBM.

The 3D architecture of native human skin is a crucial requirement in investigating the skin in health and pathologies, wound healing, and assessment of skin cosmetic and care product safety and personalized skin disease treatments. In this research, we used human skin cell lines to build fullthickness skin equivalents (FSE). Engineering artificial 3D tissue models is a known challenge in molecular biology and regenerative medicine not only due to difficulties in fabricating high-resolution scaffolds but in nondamaging monitoring of artificial tissue growth in dynamics. Here we architected 3D laser-printed scaffolds for the comfortable growth and maturation of the FSEs and also developed and validated custom-built combined fluorescence spectrometry (FS) and optical coherence tomography (OCT) imaging system for indestructible assessing metabolism and morphology of developing 3D human FSEs. This system demonstrated high sensitivity in detecting fluorescence from nicotinamide adenine dinucleotide (NADH) and riboflavin 5’-adenosine diphosphate (FAD) in solutions and cell suspensions, and high-resolution imaging of FSE morphology. Thus, our developed FSE on 3D laser-printed scaffolds and dual-mode optical system can be used in the future for nondamaging assessment of metabolism, maturation, and viability of 3D tissue models in growth dynamics.

Where OCT imaging provides high-resolution structural images in depth, dynamic OCT approaches can provide functional information. OCT signal can be divided in three categories: Static scatterers (structural OCT), flowing scatterers and scatterers entering and exiting the imaged volume. By using the signal acquired at the same position at different times, the static and flowing signals can be differentiated. Dynamic OCT has shown promising results notably in angiography [1,2] and cell activity imaging in organoids [3,4]. Using a Point-Scan Spectral Domain OCT to achieve a resolution close to cell size, a preliminary comparison of different dynamic OCT processing has been conducted to prepare further work in biological tissues.

The accuracy of optical coherence tomography angiography (OCTA) based blood flow velocimetry is affected by Axial Velocity Gradient (AVG) when the scanning beam is not perpendicular to the blood flow. We have developed two methods to eliminate the effect of AVG on amplitude decorrelation, where the AVG term is cancelled according to the established analytical model of dynamic light scattering (DLS) using two OCTA signals acquired with different spatial resolutions. We verified both solutions with flow phantom experiments. The effectiveness and limitations of both methods are discussed.