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Victor X. D. Yang

Bio: Victor X. D. Yang is an academic researcher from Sunnybrook Health Sciences Centre. The author has contributed to research in topics: Optical coherence tomography & Speckle pattern. The author has an hindex of 43, co-authored 265 publications receiving 7478 citations. Previous affiliations of Victor X. D. Yang include IPG Photonics & Women's College, Kolkata.


Papers
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Journal ArticleDOI
TL;DR: This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.
Abstract: We report on imaging of microcirculation by calculating the speckle variance of optical coherence tomography (OCT) structural images acquired using a Fourier domain mode-locked swept-wavelength laser. The algorithm calculates interframe speckle variance in two-dimensional and three-dimensional OCT data sets and shows little dependence to the Doppler angle ranging from 75 degrees to 90 degrees . We demonstrate in vivo detection of blood flow in vessels as small as 25 microm in diameter in a dorsal skinfold window chamber model with direct comparison with intravital fluorescence confocal microscopy. This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.

677 citations

Journal ArticleDOI
TL;DR: A new family of light-sensitive drugs that are designed for efficient two-photon excitation are presented and selective closure of blood vessels is demonstrated in mice using one of their new drugs, the first demonstration of in vivo photodynamic therapy using a photosensitizer engineered for efficient three-dimensional targeting.
Abstract: The spatial control of optical absorption provided by two-photon excitation has led to tremendous advances in microscopy1 and microfabrication2. Medical applications of two-photon excitation in photodynamic therapy3,4 have been widely suggested5,6,7,8,9,10,11,12,13,14,15,16,17,18, but thus far have been rendered impractical by the low two-photon cross-sections of photosensitizer drugs (which are compounds taken up by living tissues that become toxic on absorption of light). The invention of efficient two-photon activated drugs will allow precise three-dimensional manipulation of treatment volumes, providing a level of targeting unattainable with current therapeutic techniques. Here we present a new family of photodynamic therapy drugs designed for efficient two-photon excitation and use one of them to demonstrate selective closure of blood vessels through two-photon excitation photodynamic therapy in vivo. These conjugated porphyrin dimers have two-photon cross-sections that are more than two orders of magnitude greater than those of standard clinical photosensitizers17. This is the first demonstration of in vivo photodynamic therapy using a photosensitizer engineered for efficient two-photon excitation. Two-photon excitation is attractive for photodynamic therapy as it potentially allows deeper penetration within biological tissue and targeting with better precision. However, two-photon cross-sections of light-sensitive drugs are typically small, which has until now limited their practical utility. Now Anderson and colleagues have come up with a new family of light-sensitive drugs that are designed for efficient two-photon excitation. They demonstrate selective closure of blood vessels in mice using one of their new drugs.

341 citations

Journal ArticleDOI
Michael D. Hill1, Mayank Goyal1, Bijoy K Menon1, Raul G. Nogueira2  +773 moreInstitutions (39)
TL;DR: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo, and this trial is registered with ClinicalTrials.gov, NCT02930018.

321 citations

Journal ArticleDOI
TL;DR: Improvements in real-time Doppler optical coherence tomography (DOCT), acquiring up to 32 frames per second at 250 x 512 pixels per image, are reported using signal processing techniques commonly employed in Dopplers ultrasound imaging.
Abstract: Improvements in real-time Doppler optical coherence tomography (DOCT), acquiring up to 32 frames per second at 250×512 pixels per image, are reported using signal processing techniques commonly employed in Doppler ultrasound imaging. The ability to measure a wide range of flow velocities, ranging from less than 20 µm/s to more than 10 cm/s, is demonstrated using an 1.3 µm DOCT system with flow phantoms in steady and pulsatile flow conditions. Based on full implementation of a coherent demodulator, four different modes of flow visualization are demonstrated: color Doppler, velocity variance, Doppler spectrum, and power Doppler. The performance of the former two, which are computationally suitable for real-time imaging, are analyzed in detail under various signal-to-noise and frame-rate conditions. The results serve as a guideline for choosing appropriate imaging parameters for detecting in vivo blood flow.

299 citations

Journal ArticleDOI
TL;DR: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome.
Abstract: BACKGROUND: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome. METHODS: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered. FINDINGS: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30-0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69-0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81-0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low. INTERPRETATION: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. FUNDING: Medtronic.

263 citations


Cited by
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Christopher M. Bishop1
01 Jan 2006
TL;DR: Probability distributions of linear models for regression and classification are given in this article, along with a discussion of combining models and combining models in the context of machine learning and classification.
Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

10,141 citations

Journal ArticleDOI
TL;DR: The photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells as discussed by the authors, which can prolong survival in patients with inoperable cancers and significantly improve quality of life.
Abstract: Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281. V C

3,770 citations

Journal Article
TL;DR: In this article, a fast Fourier transform method of topography and interferometry is proposed to discriminate between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour generation techniques.
Abstract: A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

3,742 citations

Journal ArticleDOI
TL;DR: The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies.
Abstract: 1.1 Photodynamic Therapy and Imaging The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). In order for the reader to fully appreciate the context of the discussions embodied in this article we begin with an overview of the PDT process, starting with a brief historical perspective followed by detailed discussions of specific applications of imaging in PDT. Each section starts with an overview of the specific topic and, where appropriate, ends with summary and future directions. The review closes with the authors’ perspective of the areas of future emphasis and promise. The basic premise of this review is that a combination of imaging and PDT will provide improved research and therapeutic strategies. PDT is a photochemistry-based approach that uses a light-activatable chemical, termed a photosensitizer (PS), and light of an appropriate wavelength, to impart cytotoxicity via the generation of reactive molecular species (Figure 1a). In clinical settings, the PS is typically administered intravenously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated (Figure 1b). The time delay, often referred to as drug-light interval, between PS administration and the start of illumination with currently used PSs varies from 5 minutes to 24 hours or more depending on the specific PS and the target disease. Strictly speaking, this should be referred to as the PS-light interval, as at the concentrations typically used the PS is not a drug, but the drug-light interval terminology seems to be used fairly frequently. Typically, the useful range of wavelengths for therapeutic activation of the PS is 600 to 800 nm, to avoid interference by endogenous chromophores within the body, and yet maintain the energetics necessary for the generation of cytotoxic species (as discussed below) such as singlet oxygen (1O2). However, it is important to note that photosensitizers can also serve as fluorescence imaging agents for which activation with light in the 400nm range is often used and has been extremely useful in diagnostic imaging applications as described extensively in Section 2 of this review. The obvious limitation of short wavelength excitation is the lack of tissue penetration so that the volumes that are probed under these conditions are relatively shallow. Open in a separate window Figure 1 (A) A schematic representation of PDT where PS is a photoactivatable multifunctional agent, which, upon light activation can serve as both an imaging agent and a therapeutic agent. (B) A schematic representation of the sequence of administration, localization and light activation of the PS for PDT or fluorescence imaging. Typically the PS is delivered systemically and allowed to circulate for an appropriate time interval (the “drug-light interval”), during which the PS accumulates preferentially in the target lesion(s) prior to light activation. In the idealized depiction here the PS is accumulation is shown to be entirely in the target tissue, however, even if this is not the case, light delivery confers a second layer of selectivity so that the cytotoxic effect will be generated only in regions where both drug and light are present. Upon localization of the PS, light activation will result in fluorescence emission which can be implemented for imaging applications, as well as generation cytotoxic species for therapy. In the former case light activation is achieved with a low fluence rate to generate fluorescence emission with little or no cytotoxic effect, while in the latter case a high fluence rate is used to generate a sufficient concentration of cytotoxic species to achieve biological effects.

1,922 citations

Journal Article
TL;DR: In this article, a class of π;-conjugated compounds that exhibit large δ (as high as 1, 250 × 10−50 cm4 s per photon) and enhanced two-photon sensitivity relative to ultraviolet initiators were developed and used to demonstrate a scheme for three-dimensional data storage which permits fluorescent and refractive read-out, and the fabrication of 3D micro-optical and micromechanical structures, including photonic-bandgap-type structures.
Abstract: Two-photon excitation provides a means of activating chemical or physical processes with high spatial resolution in three dimensions and has made possible the development of three-dimensional fluorescence imaging, optical data storage, and lithographic microfabrication. These applications take advantage of the fact that the two-photon absorption probability depends quadratically on intensity, so under tight-focusing conditions, the absorption is confined at the focus to a volume of order λ3 (where λ is the laser wavelength). Any subsequent process, such as fluorescence or a photoinduced chemical reaction, is also localized in this small volume. Although three-dimensional data storage and microfabrication have been illustrated using two-photon-initiated polymerization of resins incorporating conventional ultraviolet-absorbing initiators, such photopolymer systems exhibit low photosensitivity as the initiators have small two-photon absorption cross-sections (δ). Consequently, this approach requires high laser power, and its widespread use remains impractical. Here we report on a class of π;-conjugated compounds that exhibit large δ (as high as 1, 250 × 10−50 cm4 s per photon) and enhanced two-photon sensitivity relative to ultraviolet initiators. Two-photon excitable resins based on these new initiators have been developed and used to demonstrate a scheme for three-dimensional data storage which permits fluorescent and refractive read-out, and the fabrication of three-dimensional micro-optical and micromechanical structures, including photonic-bandgap-type structures.

1,833 citations