1,720,991 research outputs found
Development of a High Resolution Microvascular Imaging Toolkit for Optical Coherence Tomography
No full textThis thesis presents the development of new optical coherence tomography imaging systems and techniques to improve in vivo 3D microvascular imaging. Specifically these systems and techniques were proposed to address three main problems with 3D Doppler optical coherence tomography imaging: (a) Motion artefacts, (b) angle dependence of the signal, and (c) relatively high minimum detectable velocity of conventional color Doppler algorithms (~500 μm/s). In order to overcome these limitations a multi-pronged strategy was employed: (1) Construction of a retrospectively gated OCT system for the mitigation of periodic motion artefacts. Proof of principle in vivo B-mode imaging of Xenopus Laevis (embryo of African clawed frog) cardiovascular function up to 1000 frames per second (fps) from data acquired at 12 fps. Additionally, 4D imaging of the Xenopus Laevis heart at 45 volumes per second was demonstrated. (2) Construction of a Fourier domain mode locked laser for high speed swept source optical coherence tomography imaging. This laser was capable of reaching sweep rates of 67 kHz and was optimized to function in the SNR limited phase noise regimes upto approximately 55 dB structural SNR. (3) Development of a novel speckle variance image processing algorithm for velocity and angle independent 3D microvascular imaging. The velocity and angle independence of the technique was validated through phantom studies.
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In vivo demonstration of the speckle variance algorithm was performed by imaging the capillary network in the dorsal skin-fold window chamber model, with the results being validated using fluorescence confocal microscopy. In the final part of this thesis, these newly developed technologies were applied to the assessment of anti-vascular and anti-angiogenic therapies in preclinical models, specifically, photodynamic therapy and targeted degradation of HIF-α.Ph
Two-photon Microscopy and Polarimetry for Assessment of Myocardial Tissue Organization
Get PDFOptical methods can provide useful tissue characterization tools. For this project, two-photon microscopy and polarized light examinations (polarimetry) were used to assess the organizational state of myocardium in healthy, infarcted, and stem-cell regenerated states. Two-photon microscopy visualizes collagen through second-harmonic generation and myocytes through two-photon excitation autofluorescence, providing information on the composition and structure/organization of the tissue. Polarimetry measurements yield a value of linear retardance that can serve as an indicator of tissue anisotropy, and with a dual-projection method, information about the anisotropy axis orientation can also be extracted. Two-photon microscopy results reveal that stem-cell treated tissue retains more myocytes and structure than infarcted myocardium, while polarimetry findings suggest that the injury caused by temporary ligation of a coronary artery is less severe
and more diffuse that than caused by a permanent ligation. Both these methods show
potential for tissue characterization.MAS
Depolarization of backscattered light from turbid media: influence of scatterer size and applications in tumour assessment
No full textPolarization remains an under-utilized optical property in biophotonics, however, recent progress in polarized light science has enabled a growing number of promising demonstrations in tumour detection/assessment applications. An interesting polarimetric property, known as depolarization, has been a subject of interest in polarimetry due to its differential response between cancerous and non-cancerous tissues; however, our understanding of this depolarization-based contrast remains limited. Interestingly, depolarization is known to be sensitive to the ‘scatterer size’ property in media which quantifies the optically apparent size of scattering particles/interfaces. Additionally, scatterer size is thought to change during cancer progression due to morphological alterations, but there is conflicting evidence on whether it increases or decreases. Thus, in order to advance the use of depolarization for tumour detection/assessment applications, its behaviour in heterogeneous media and its relationship with scatterer size require further investigation.
The work in this dissertation investigates how scatterer size modulates the depolarization of backscattered linearly and circularly polarized light from microsphere suspensions and biological tissues. Insights into these relationships enable (1) useful exploitations of depolarization for tumour assessment, and (2) more informed interpretations of polarimetric images. Scatterer size is found to modulate linear and circular depolarization by influencing single-scattering directionality (i.e., phase functions) which then influences multiple scattering pathways of backscattered light – these pathways are shown to modulate depolarization rates. Through these studies, certain depolarization signatures are found to be associated with small Rayleigh-regime scatterers and large non-Rayleigh regime scatterers. Interestingly, tumour tissues are found to exhibit Rayleigh-associated depolarization signatures, which lends insight into depolarization-based contrast between tumour and non-tumour tissue.Ph.D
Polarimetry for Breast Cancer Imaging
No full textMedical imaging is vital to the successful management of breast cancer. This thesis investigated polarimetry for breast cancer imaging. Polarimetry is the use of polarized light to study properties of matter. The main contributions of this thesis can be divided into those which expand the capabilities of experimental polarimetry, and those which explore polarimetry as a method for breast cancer imaging.
Towards an improved polarimetry platform, work was done to test the importance of appropriately selecting which types of polarized light to use for polarimetry measurements. Specifically, an optimum set of input polarization states was experimentally validated for use with a dual photoelastic modulator (PEM) polarimeter. Further, two new polarimetry imaging systems were developed. The first was designed to enable faster polarimetry imaging. A rapid imaging system based on PEMs and a charge-coupled device (CCD) camera was built, calibrated, and used to image biological phantoms. The second imaging system was designed to enable accessible multiscale polarimetry imaging. A removable polarimetry module was designed and built for use with a commercial microscope.
Polarimetry was investigated as an imaging method for two important aspects of breast cancer, specifically, breast cancer margins, and collagen organization. The breast cancer margin work was done in the context of providing image-guidance for mass spectrometry. Mass spectrometry is a technique for sensitively acquiring tissue chemical signatures, but is hindered by long imaging times. Polarimetry was found to rapidly differentiate human breast cancer from healthy tissue in a mouse model of breast cancer. It could also identify necrosis in breast cancer lymph node metastases. These findings are promising for polarimetry-guided mass spectrometry. Finally, polarimetry was investigated for imaging collagen organization in a mouse model of breast cancer. A direct comparison with second harmonic generation (SHG) imaging found that polarimetry detects organizational contrast different from that arising exclusively from collagen.
Polarimetry shows potential for breast cancer imaging, whether on its own or paired with other techniques such as mass spectrometry. The hope is that the findings of this thesis will help guide the continued development of polarimetry, both for breast cancer, and biomedicine in general.Ph.D
Development and Use of Polarized Light Methods to Assess Structure and Composition of Biological Tissue
No full textThe use of polarized light for characterization of biological tissues has received increased attention in recent years due to the wealth of information available in the interactions of polarized light with tissue and the noninvasive nature of optical radiation. While the depolarizing effects of multiple scattering complicate the use of polarimetry in tissue, many biological constituents affect the polarization of light such as collagen, muscle fibers, and glucose. Thus, if the effects of scattering can be accounted for⎯or utilized in the analysis⎯polarized light can potentially be used as a probe of tissue status.
This thesis presents advancements in the techniques for the simulation of polarized light in tissue-simulating media, and explores two biomedical applications. Previous Monte Carlo models for simulation of polarized light propagation in tissue-simulating media do not include the effects of birefringence and optical activity, two polarizing effects of useful diagnostic potential. To overcome this limitation, our model was extended to include both these effects simultaneously, and then experimentally validated using a novel polarization phantom system. The use of polarized light for characterization of the myocardium, and specifically towards monitoring stem cell regenerative treatments of myocardial infarction, was investigated experimentally as a novel application for polarimetry. The potential for this technique is based on the changes in myocardial structure that occur with infarction and subsequent regeneration, and the associated changes in tissue birefringence. The use of polarized light for noninvasive tissue analyte monitoring, particularly glucose, was also investigated based on the optical activity exhibited by many tissue analytes due to their chiral structure. In this study, a novel combined optical polarization and intensity approach was developed and tested on Monte Carlo simulated data. The studies presented in thesis introduce new methods for polarization simulation and analysis in biological tissue and demonstrate potential for polarimetry in monitoring myocardial regeneration and noninvasive measurements of tissue analytes.Ph
High-resolution deep-tissue optical imaging using anti-Stokes phosphors
No full textWe report on the high-resolution deep-tissue imaging using novel water-dispersible upconversion nanoparticles (UCNPs) β-NaYF4:Yb 3+:Tm3+. Luminescence from the UCNP embedded into tissue-mimicking phantoms at the depth of 4 mm epi-illuminated with 975-nm laser radiation was detected. Fiber-optic detection shows 2-times better resolution compared with that obtained using CCD-based imaging modality. The conversion efficiency of upconversion particles and their cytotoxicity to HeLa cells were also investigated and reported.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Quantification of Microvascular Response to Ionizing Radiation with Speckle Variance Optical Coherence Tomography
Get PDFCancer cells require access to blood vessels for oxygen and nutrients to enable growth and metastasis, making the tumour vasculature an attractive potential target for cancer therapies. Recent evidence suggests that the tumour vasculature plays a significant role in tumour response to high dose radiation therapy; however this effect is not well characterized due to limitations in quantitative imaging of the microvasculature.
Speckle variance optical coherence tomography is an emerging imaging modality capable of 3D, non-invasive imaging of in vivo microvasculature. This thesis outlines the work done to test the hypothesis that svOCT imaging can be used to quantitatively monitor the vascular effects of high dose radiotherapy in a preclinical model. This was achieved through the development of a quantification pipeline for longitudinal 3-D svOCT images of microvascular radioresponse.MAS
Polarized Light Microscopy of Human Breast Cancer
Get PDFIt has been shown that the stroma surrounding the tumour can play an important role in cancer behaviour and response to therapy.
Polarimetry may be a suitable technique for this application because collagen, a fibrous component of stroma, is anisotropic and interacts strongly with polarized light. Polarimetry is also attractive because it is rapid, widefield, and non-ionizing.
We proposed a novel and relatively simple methodology of polarized light microscopy to image thin, unstained histology slides using only crossed linear polarizers. The brightness of birefringent structures under crossed polarizers is dependent on the relative orientation of the structures and the polarizers. By imaging slides at various orientations, we can obtain retardance and fast axis orientation images, important measures of tissue biophysics. From images acquired, morphological features describing the density and alignment of the stroma within the tumour microenvironment are extracted to be used in a future breast cancer prognostication tool.M.Sc
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