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Sergei A Vinogradov - One of the best experts on this subject based on the ideXlab platform.

  • merger of dynamic two photon and Phosphorescence Lifetime microscopy reveals dependence of lymphocyte motility on oxygen in solid and hematological tumors
    Journal for ImmunoTherapy of Cancer, 2019
    Co-Authors: Mateusz Rytelewski, Sergei A Vinogradov, Karine Haryutyunan, Felix Nwajei, Meenakshi Shanmugasundaram, Patrick Wspanialy, Chao Hsien Chen, Mirna El Khatib, Shane Plunkett, Marina Konopleva
    Abstract:

    Low availability of oxygen in tumors contributes to the hostility of the tumor microenvironment toward the immune system. However, the dynamic relationship between local oxygen levels and the immune surveillance of tumors by tumor infiltrating T-lymphocytes (TIL) remains unclear. This situation reflects a methodological difficulty in visualizing oxygen gradients in living tissue in a manner that is suitable for spatiotemporal quantification and contextual correlation with individual cell dynamics tracked by typical fluorescence reporter systems. Here, we devise a regimen for intravital oxygen and cell dynamics co-imaging, termed ‘Fast’ Scanning Two-photon Phosphorescence Lifetime Imaging Microscopy (FaST-PLIM). Using FaST-PLIM, we image the cellular motility of T-lymphocytes in relation to the microscopic distribution of oxygen in mouse models of hematological and solid tumors, namely in bone marrow with or without B-cell acute lymphocytic leukemia (ALL), and in lungs with sarcoma tumors. Both in bone marrow leukemia and solid tumor models, TILs encountered regions of varying oxygen concentrations, including regions of hypoxia (defined as pO2 below 5 mmHg), especially in advanced-stage ALL and within solid tumor cores. T cell motility was sustained and weakly correlated with local pO2 above 5 mmHg but it was very slow in pO2 below this level. In solid tumors, this relationship was reflected in slow migration of TIL in tumor cores compared to that in tumor margins. Remarkably, breathing 100% oxygen alleviated tumor core hypoxia and rapidly invigorated the motility of otherwise stalled tumor core TILs. This study demonstrates a versatile and highly contextual FaST-PLIM method for Phosphorescence Lifetime-based oxygen imaging in living animal tumor immunology models. The initial results of this method application to ALL and solid lung tumor models highlight the importance of oxygen supply for the maintenance of intratumoral T cell migration, define a 5 mmHg local oxygen concentration threshold for TIL motility, and demonstrate efficacy of supplementary oxygen breathing in TIL motility enhancement coincident with reduction of tumor hypoxia.

  • two photon Phosphorescence Lifetime microscopy of retinal capillary plexus oxygenation in mice
    Journal of Biomedical Optics, 2018
    Co-Authors: Ikbal şencan, David A Boas, Sergei A Vinogradov, Mahnaz Shahidi, Tatiana V Esipova, Mohammad A Yaseen, Buyin Fu, Sava Sakadžic
    Abstract:

    Impaired oxygen delivery and/or consumption in the retinal tissue underlies the pathophysiology of many retinal diseases. However, the essential tools for measuring oxygen concentration in retinal capillaries and studying oxygen transport to retinal tissue are still lacking. We show that two-photon Phosphorescence Lifetime microscopy can be used to map absolute partial pressures of oxygen (pO2) in the retinal capillary plexus. Measurements were performed at various retinal depths in anesthetized mice under systemic normoxic and hyperoxic conditions. We used a newly developed two-photon phosphorescent oxygen probe, based on a two-photon absorbing platinum tetraphthalimidoporphyrin, and commercially available optics without correction for optical aberrations of the eye. The transverse and axial distances within the tissue volume were calibrated using a model of the eye’s optical system. We believe this is the first demonstration of in vivo depth-resolved imaging of pO2 in retinal capillaries. Application of this method has the potential to advance our understanding of oxygen delivery on the microvascular scale and help elucidate mechanisms underlying various retinal diseases.

  • two photon Phosphorescence Lifetime microscopy 2plm for high resolution imaging of oxygen
    Proceedings of SPIE, 2011
    Co-Authors: Louise E Sinks, Sava Sakadžic, David A Boas, Emmanuel Roussakis, Gregory P Robbins, Daniel A Hammer, Anna Devor, Sergei A Vinogradov
    Abstract:

    We present a new method for imaging of oxygen in biological samples with micron-scale resolution and threedimensional capability. Our technique combines Phosphorescence quenching with multiphoton laser scanning microscopy. It is termed two-photon Phosphorescence Lifetime microscopy (2PLM). 2PLM is made possible due to specially designed dendritic probes, in which Phosphorescence of metalloporphyrins upon two-photon excitation is enhanced by intramolecular Forster-type energy transfer from two-photon antennae chromophores, located in the same probe molecule. Oxygen sensitivity of the probes is regulated by dendritic encapsulation of the core metalloporphyrin, while peripheral PEG groups on the dendrimer isolate the probes from contacts with biological macromolecules (e.g. proteins, nucleic acids etc) in the environment. Instrumentation and resolution of the method are discussed along with approaches to intracellular delivery of the probes. 2PLM was validated in pilot imaging experiments and used to obtain depth-resolved high-resolution oxygen maps in vivo in the brain.

  • influence of optical heterogeneities on reconstruction of spatial Phosphorescence Lifetime distributions
    Optics Letters, 2008
    Co-Authors: Sofia Apreleva, Sergei A Vinogradov
    Abstract:

    We have previously demonstrated that Phosphorescence Lifetime imaging (PLI) allows for unbiased determination of absolute oxygen levels in homogeneously absorbing/scattering media. We computationally show that tomographic PLI can perform equally well in heterogeneous environments relying only on surface measurements of Phosphorescence.

  • Phosphorescence Lifetime tomography in optically heterogeneous media
    IEEE Transactions on Biomedical Engineering, 2008
    Co-Authors: Sofia Apreleva, Sergei A Vinogradov
    Abstract:

    We have previously demonstrated that Phosphorescence Lifetime imaging (PLI) allows determination of oxygen in homogeneously absorbing/scattering media. Herein we show that PLI can perform equally well in heterogeneous environments relying only on measurements of Phosphorescence.

Isa Yildirim - One of the best experts on this subject based on the ideXlab platform.

  • a fast regularized least squares method for retinal vascular oxygen tension estimation using a Phosphorescence Lifetime imaging model
    Biomedical Engineering Online, 2013
    Co-Authors: Gokhan Gunay, Isa Yildirim
    Abstract:

    Background Monitoring retinal oxygenation is of primary importance in detecting the presence of some common eye diseases. To improve the estimation of oxygen tension in retinal vessels, regularized least-squares (RLS) method was shown to be very effective compared with the conventional least-squares (LS) estimation. In this study, we propose an accelerated RLS estimation method for the problem of assessing the oxygenation of retinal vessels from Phosphorescence Lifetime images.

  • A fast regularized least-squares method for retinal vascular oxygen tension estimation using a Phosphorescence Lifetime imaging model.
    Biomedical Engineering Online, 2013
    Co-Authors: Gokhan Gunay, Isa Yildirim
    Abstract:

    Background: Monitoring retinal oxygenation is of primary importance in detecting the presence of some common eye diseases. To improve the estimation of oxygen tension in retinal vessels, regularized least-squares (RLS) method was shown to be very effective compared with the conventional least-squares (LS) estimation. In this study, we propose an accelerated RLS estimation method for the problem of assessing the oxygenation of retinal vessels from Phosphorescence Lifetime images. Methods: In the previous work, gradient descent algorithms were used to find the minimum of the RLS cost function. This approach is computationally expensive, especially when the oxygen tension map is large. In this study, using a closed-form solution of the RLS estimation and some inherent properties of the problem at hand, the RLS process is reduced to the weighted averaging of the LS estimates. This decreases the computational complexity of the RLS estimation considerably without sacrificing its performance. Results: Performance analyses are conducted using both real and simulated data sets. In terms of computational complexity, the proposed RLS estimation method is significantly better than RLS methods that use gradient descent algorithms to find the minimum of the cost function. Additionally, there is no significant difference between the estimates acquired by the proposed and conventional RLS estimation methods. Conclusion: The proposed RLS estimation method for computing the retinal oxygen tension is computationally efficient, and produces estimates with negligible difference from those obtained by iterative RLS methods. Further, the results of this study can be applied to other Lifetime imaging problems that have similar properties.

  • Map estimation of oxygen tension in retinal vessels with Phosphorescence Lifetime imaging
    2012 9th IEEE International Symposium on Biomedical Imaging (ISBI), 2012
    Co-Authors: Isa Yildirim, Rashid Ansari
    Abstract:

    In Phosphorescence Lifetime imaging methods oxygen tension in retinal vessels has traditionally been indirectly determined from the estimates of intermediate variables whose noise-contaminated linear combinations are observed as Phosphorescence intensity images. The classical least squares (LS) and regularized least squares (RLS) methods were used to obtain estimates of the intermediate variables. The estimates of the intermediate variables are then used to compute oxygen tension. The estimates of intermediate variables, however, do not yield an optimum estimate of oxygen tension due to its nonlinear dependence on the ratio of intermediate variables. Moreover, prior knowledge about the variables is very limited so that the level of noise cannot be reliably estimated, thereby affecting the automated choice of the regularization parameter in the RLS method. In this study the problem of optimally estimating oxygen tension in retinal vessels using the maximum a posteriori (MAP) criterion is addressed. For this purpose the conditional distribution of oxygen tension is derived given the Phosphorescence Lifetime imaging observations and model. The performance of MAP is compared with that of LS and the RLS methods using simulated data and its improved performance in the presence of different levels of noise is demonstrated.

  • ISBI - Map estimation of oxygen tension in retinal vessels with Phosphorescence Lifetime imaging
    2012 9th IEEE International Symposium on Biomedical Imaging (ISBI), 2012
    Co-Authors: Isa Yildirim, Rashid Ansari
    Abstract:

    In Phosphorescence Lifetime imaging methods oxygen tension in retinal vessels has traditionally been indirectly determined from the estimates of intermediate variables whose noise-contaminated linear combinations are observed as Phosphorescence intensity images. The classical least squares (LS) and regularized least squares (RLS) methods were used to obtain estimates of the intermediate variables. The estimates of the intermediate variables are then used to compute oxygen tension. The estimates of intermediate variables, however, do not yield an optimum estimate of oxygen tension due to its nonlinear dependence on the ratio of intermediate variables. Moreover, prior knowledge about the variables is very limited so that the level of noise cannot be reliably estimated, thereby affecting the automated choice of the regularization parameter in the RLS method. In this study the problem of optimally estimating oxygen tension in retinal vessels using the maximum a posteriori (MAP) criterion is addressed. For this purpose the conditional distribution of oxygen tension is derived given the Phosphorescence Lifetime imaging observations and model. The performance of MAP is compared with that of LS and the RLS methods using simulated data and its improved performance in the presence of different levels of noise is demonstrated.

  • ISBI - Estimation of oxygen tension in retinal capillaries from Phosphorescence Lifetime images
    2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
    Co-Authors: Isa Yildirim, Justin Wanek, Rashid Ansari, I. Samil Yetik, Mahnaz Shahidi
    Abstract:

    Investigating the effect of retinal oxygenation abnormalities in the development of common eye diseases requires accurate assessment of oxygen tension in retinal vasculatures. Estimation of oxygen tension in retinal capillaries using Phosphorescence Lifetime imaging is addressed in this paper. Separation from tissue and oxygen tension estimation is a more challenging task for capillaries when compared with large retinal vessels due to the finer structure and noise predominance in capillaries. An automated segmentation procedure is applied using the EM algorithm and noise contamination is reduced using a regularization method unlike previous approaches to capillary analysis where segmentation was done manually and noise contamination was ignored. We demonstrate the effectiveness of the proposed method by applying it to the retinal image data acquired from rat eyes, and we show that the oxygen tension estimate of retinal capillaries falls in the physiologically expected range.

Mahnaz Shahidi - One of the best experts on this subject based on the ideXlab platform.

  • two photon Phosphorescence Lifetime microscopy of retinal capillary plexus oxygenation in mice
    Journal of Biomedical Optics, 2018
    Co-Authors: Ikbal şencan, David A Boas, Sergei A Vinogradov, Mahnaz Shahidi, Tatiana V Esipova, Mohammad A Yaseen, Buyin Fu, Sava Sakadžic
    Abstract:

    Impaired oxygen delivery and/or consumption in the retinal tissue underlies the pathophysiology of many retinal diseases. However, the essential tools for measuring oxygen concentration in retinal capillaries and studying oxygen transport to retinal tissue are still lacking. We show that two-photon Phosphorescence Lifetime microscopy can be used to map absolute partial pressures of oxygen (pO2) in the retinal capillary plexus. Measurements were performed at various retinal depths in anesthetized mice under systemic normoxic and hyperoxic conditions. We used a newly developed two-photon phosphorescent oxygen probe, based on a two-photon absorbing platinum tetraphthalimidoporphyrin, and commercially available optics without correction for optical aberrations of the eye. The transverse and axial distances within the tissue volume were calibrated using a model of the eye’s optical system. We believe this is the first demonstration of in vivo depth-resolved imaging of pO2 in retinal capillaries. Application of this method has the potential to advance our understanding of oxygen delivery on the microvascular scale and help elucidate mechanisms underlying various retinal diseases.

  • outer retinal oxygen consumption of rat by Phosphorescence Lifetime imaging
    Current Eye Research, 2012
    Co-Authors: Justin Wanek, Norman P. Blair, Mahnaz Shahidi
    Abstract:

    Purpose: Since the metabolic function of the retinal tissue is altered due to physiologic changes or disease, measurements of outer retinal oxygen consumption (QOR) may be beneficial in assessment of retinal status. The purpose of this study was to report measurements of QOR in rats using a Phosphorescence Lifetime imaging technique.Methods: Phosphorescence Lifetime imaging was performed and retinal PO2 maps were generated in 10 rats under a light-adapted condition. Depth-resolved retinal PO2 profiles were derived from the PO2 maps. From the profiles, the maximum outer retina PO2 (PmaxO2) was obtained and QOR was calculated using a one-dimensional oxygen diffusion model. Repeatability, inter-location variability, and inter-subject variability of PmaxO2 and QOR measurements were established.Results: Intraclass correlation coefficients of repeated measurements of PmaxO2 and QOR were 0.89 and 0.70, respectively (P < 0.001). Inter-location variability of PmaxO2 and QOR measurements at superior to inferior con...

  • Outer Retinal Oxygen Consumption of Rat by Phosphorescence Lifetime Imaging
    Current Eye Research, 2011
    Co-Authors: Justin Wanek, Norman P. Blair, Mahnaz Shahidi
    Abstract:

    Purpose: Since the metabolic function of the retinal tissue is altered due to physiologic changes or disease, measurements of outer retinal oxygen consumption (QOR) may be beneficial in assessment of retinal status. The purpose of this study was to report measurements of QOR in rats using a Phosphorescence Lifetime imaging technique.Methods: Phosphorescence Lifetime imaging was performed and retinal PO2 maps were generated in 10 rats under a light-adapted condition. Depth-resolved retinal PO2 profiles were derived from the PO2 maps. From the profiles, the maximum outer retina PO2 (PmaxO2) was obtained and QOR was calculated using a one-dimensional oxygen diffusion model. Repeatability, inter-location variability, and inter-subject variability of PmaxO2 and QOR measurements were established.Results: Intraclass correlation coefficients of repeated measurements of PmaxO2 and QOR were 0.89 and 0.70, respectively (P 

  • ISBI - Estimation of oxygen tension in retinal capillaries from Phosphorescence Lifetime images
    2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
    Co-Authors: Isa Yildirim, Justin Wanek, Rashid Ansari, I. Samil Yetik, Mahnaz Shahidi
    Abstract:

    Investigating the effect of retinal oxygenation abnormalities in the development of common eye diseases requires accurate assessment of oxygen tension in retinal vasculatures. Estimation of oxygen tension in retinal capillaries using Phosphorescence Lifetime imaging is addressed in this paper. Separation from tissue and oxygen tension estimation is a more challenging task for capillaries when compared with large retinal vessels due to the finer structure and noise predominance in capillaries. An automated segmentation procedure is applied using the EM algorithm and noise contamination is reduced using a regularization method unlike previous approaches to capillary analysis where segmentation was done manually and noise contamination was ignored. We demonstrate the effectiveness of the proposed method by applying it to the retinal image data acquired from rat eyes, and we show that the oxygen tension estimate of retinal capillaries falls in the physiologically expected range.

  • Estimation of oxygen tension in retinal capillaries from Phosphorescence Lifetime images
    2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
    Co-Authors: Isa Yildirim, Justin Wanek, Rashid Ansari, Samil I. Yetik, Mahnaz Shahidi
    Abstract:

    Investigating the effect of retinal oxygenation abnormalities in the development of common eye diseases requires accurate assessment of oxygen tension in retinal vasculatures. Estimation of oxygen tension in retinal capillaries using Phosphorescence Lifetime imaging is addressed in this paper. Separation from tissue and oxygen tension estimation is a more challenging task for capillaries when compared with large retinal vessels due to the finer structure and noise predominance in capillaries. An automated segmentation procedure is applied using the EM algorithm and noise contamination is reduced using a regularization method unlike previous approaches to capillary analysis where segmentation was done manually and noise contamination was ignored. We demonstrate the effectiveness of the proposed method by applying it to the retinal image data acquired from rat eyes, and we show that the oxygen tension estimate of retinal capillaries falls in the physiologically expected range.

Fernando B Dias - One of the best experts on this subject based on the ideXlab platform.

Rashid Ansari - One of the best experts on this subject based on the ideXlab platform.

  • Map estimation of oxygen tension in retinal vessels with Phosphorescence Lifetime imaging
    2012 9th IEEE International Symposium on Biomedical Imaging (ISBI), 2012
    Co-Authors: Isa Yildirim, Rashid Ansari
    Abstract:

    In Phosphorescence Lifetime imaging methods oxygen tension in retinal vessels has traditionally been indirectly determined from the estimates of intermediate variables whose noise-contaminated linear combinations are observed as Phosphorescence intensity images. The classical least squares (LS) and regularized least squares (RLS) methods were used to obtain estimates of the intermediate variables. The estimates of the intermediate variables are then used to compute oxygen tension. The estimates of intermediate variables, however, do not yield an optimum estimate of oxygen tension due to its nonlinear dependence on the ratio of intermediate variables. Moreover, prior knowledge about the variables is very limited so that the level of noise cannot be reliably estimated, thereby affecting the automated choice of the regularization parameter in the RLS method. In this study the problem of optimally estimating oxygen tension in retinal vessels using the maximum a posteriori (MAP) criterion is addressed. For this purpose the conditional distribution of oxygen tension is derived given the Phosphorescence Lifetime imaging observations and model. The performance of MAP is compared with that of LS and the RLS methods using simulated data and its improved performance in the presence of different levels of noise is demonstrated.

  • ISBI - Map estimation of oxygen tension in retinal vessels with Phosphorescence Lifetime imaging
    2012 9th IEEE International Symposium on Biomedical Imaging (ISBI), 2012
    Co-Authors: Isa Yildirim, Rashid Ansari
    Abstract:

    In Phosphorescence Lifetime imaging methods oxygen tension in retinal vessels has traditionally been indirectly determined from the estimates of intermediate variables whose noise-contaminated linear combinations are observed as Phosphorescence intensity images. The classical least squares (LS) and regularized least squares (RLS) methods were used to obtain estimates of the intermediate variables. The estimates of the intermediate variables are then used to compute oxygen tension. The estimates of intermediate variables, however, do not yield an optimum estimate of oxygen tension due to its nonlinear dependence on the ratio of intermediate variables. Moreover, prior knowledge about the variables is very limited so that the level of noise cannot be reliably estimated, thereby affecting the automated choice of the regularization parameter in the RLS method. In this study the problem of optimally estimating oxygen tension in retinal vessels using the maximum a posteriori (MAP) criterion is addressed. For this purpose the conditional distribution of oxygen tension is derived given the Phosphorescence Lifetime imaging observations and model. The performance of MAP is compared with that of LS and the RLS methods using simulated data and its improved performance in the presence of different levels of noise is demonstrated.

  • ISBI - Estimation of oxygen tension in retinal capillaries from Phosphorescence Lifetime images
    2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
    Co-Authors: Isa Yildirim, Justin Wanek, Rashid Ansari, I. Samil Yetik, Mahnaz Shahidi
    Abstract:

    Investigating the effect of retinal oxygenation abnormalities in the development of common eye diseases requires accurate assessment of oxygen tension in retinal vasculatures. Estimation of oxygen tension in retinal capillaries using Phosphorescence Lifetime imaging is addressed in this paper. Separation from tissue and oxygen tension estimation is a more challenging task for capillaries when compared with large retinal vessels due to the finer structure and noise predominance in capillaries. An automated segmentation procedure is applied using the EM algorithm and noise contamination is reduced using a regularization method unlike previous approaches to capillary analysis where segmentation was done manually and noise contamination was ignored. We demonstrate the effectiveness of the proposed method by applying it to the retinal image data acquired from rat eyes, and we show that the oxygen tension estimate of retinal capillaries falls in the physiologically expected range.

  • Estimation of oxygen tension in retinal capillaries from Phosphorescence Lifetime images
    2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
    Co-Authors: Isa Yildirim, Justin Wanek, Rashid Ansari, Samil I. Yetik, Mahnaz Shahidi
    Abstract:

    Investigating the effect of retinal oxygenation abnormalities in the development of common eye diseases requires accurate assessment of oxygen tension in retinal vasculatures. Estimation of oxygen tension in retinal capillaries using Phosphorescence Lifetime imaging is addressed in this paper. Separation from tissue and oxygen tension estimation is a more challenging task for capillaries when compared with large retinal vessels due to the finer structure and noise predominance in capillaries. An automated segmentation procedure is applied using the EM algorithm and noise contamination is reduced using a regularization method unlike previous approaches to capillary analysis where segmentation was done manually and noise contamination was ignored. We demonstrate the effectiveness of the proposed method by applying it to the retinal image data acquired from rat eyes, and we show that the oxygen tension estimate of retinal capillaries falls in the physiologically expected range.

  • Regularized Estimation of Retinal Vascular Oxygen Tension From Phosphorescence Images
    IEEE Transactions on Biomedical Engineering, 2009
    Co-Authors: Isa Yildirim, Justin Wanek, Rashid Ansari, I. Samil Yetik, Mahnaz Shahidi
    Abstract:

    The level of retinal oxygenation is potentially an important cue to the onset or presence of some common retinal diseases. An improved method for assessing oxygen tension in retinal blood vessels from Phosphorescence Lifetime imaging data is reported in this paper. The optimum estimate for Phosphorescence Lifetime and oxygen tension is obtained by regularizing the least-squares (LS) method. The estimation method is implemented with an iterative algorithm to minimize a regularized LS cost function. The effectiveness of the proposed method is demonstrated by applying it to simulated data as well as image data acquired from rat retinas. The method is shown to yield estimates that are robust to noise and whose variance is lower than that obtained with the classical LS method.