Browsing by Author "Zhang, Xiaofeng"

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    Cherenkov emissions for studying tumor changes during radiation therapy: An exploratory study in domesticated dogs with naturally-occurring cancer.
    (PloS one, 2020-01) Rickard, Ashlyn G; Yoshikawa, Hiroto; Palmer, Gregory M; Liu, Harrison Q; Dewhirst, Mark W; Nolan, Michael W; Zhang, Xiaofeng

    Purpose

    Real-time monitoring of physiological changes of tumor tissue during radiation therapy (RT) could improve therapeutic efficacy and predict therapeutic outcomes. Cherenkov radiation is a normal byproduct of radiation deposited in tissue. Previous studies in rat tumors have confirmed a correlation between Cherenkov emission spectra and optical measurements of blood-oxygen saturation based on the tissue absorption coefficients. The purpose of this study is to determine if it is feasible to image Cherenkov emissions during radiation therapy in larger human-sized tumors of pet dogs with cancer. We also wished to validate the prior work in rats, to determine if Cherenkov emissions have the potential to act an indicator of blood-oxygen saturation or water-content changes in the tumor tissue-both of which have been correlated with patient prognosis.

    Methods

    A DoseOptics camera, built to image the low-intensity emission of Cherenkov radiation, was used to measure Cherenkov intensities in a cohort of cancer-bearing pet dogs during clinical irradiation. Tumor type and location varied, as did the radiation fractionation scheme and beam arrangement, each planned according to institutional standard-of-care. Unmodulated radiation was delivered using multiple 6 MV X-ray beams from a clinical linear accelerator. Each dog was treated with a minimum of 16 Gy total, in ≥3 fractions. Each fraction was split into at least three subfractions per gantry angle. During each subfraction, Cherenkov emissions were imaged.

    Results

    We documented significant intra-subfraction differences between the Cherenkov intensities for normal tissue, whole-tumor tissue, tissue at the edge of the tumor and tissue at the center of the tumor (p<0.05). Additionally, intra-subfraction changes suggest that Cherenkov emissions may have captured fluctuating absorption properties within the tumor.

    Conclusion

    Here we demonstrate that it is possible to obtain Cherenkov emissions from canine cancers within a fraction of radiotherapy. The entire optical spectrum was obtained which includes the window for imaging changes in water and hemoglobin saturation. This lends credence to the goal of using this method during radiotherapy in human patients and client-owned pets.
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    Construction of the Jacobian matrix for fluorescence diffuse optical tomography using a perturbation Monte Carlo method.
    (Proc SPIE Int Soc Opt Eng, 2012-02-13) Zhang, Xiaofeng
    Image formation in fluorescence diffuse optical tomography is critically dependent on construction of the Jacobian matrix. For clinical and preclinical applications, because of the highly heterogeneous characteristics of the medium, Monte Carlo methods are frequently adopted to construct the Jacobian. Conventional adjoint Monte Carlo method typically compute the Jacobian by multiplying the photon density fields radiated from the source at the excitation wavelength and from the detector at the emission wavelength. Nonetheless, this approach assumes that the source and the detector in Green's function are reciprocal, which is invalid in general. This assumption is particularly questionable in small animal imaging, where the mean free path length of photons is typically only one order of magnitude smaller than the representative dimension of the medium. We propose a new method that does not rely on the reciprocity of the source and the detector by tracing photon propagation entirely from the source to the detector. This method relies on the perturbation Monte Carlo theory to account for the differences in optical properties of the medium at the excitation and the emission wavelengths. Compared to the adjoint methods, the proposed method is more valid in reflecting the physical process of photon transport in diffusive media and is more efficient in constructing the Jacobian matrix for densely sampled configurations.
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    Detectability of absorption and reduced scattering coefficients in frequency-domain measurements using a realistic head phantom.
    (Sensors (Basel), 2012-12-24) Zhang, Xiaofeng; Webb, Andrew
    Detection limits of the changes in absorption and reduced scattering coefficients were investigated using a frequency-domain near-infrared system in a realistic head phantom. The results were quantified in terms of the maximum detectable depth for different activation volumes in the range of 0.8-20 microliters. The non-linear relation between the maximum detectable depth and the magnitude of changes in the absorption coefficient conform well with the Born approximation to the diffusion equation. The minimal detectable changes in the reduced scattering coefficient measured in terms of the phase signal were found to be approximately twice as large as that of the absorption coefficient using the AC signal for the same volume and at the same depth. The phase delay, which can be used to quantify the fast neuronal optical response in the human brain, showed a linear dependence on the reciprocal of the reduced scattering coefficient, as predicted by the Rytov approximation.
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    Enhancing Radiation Therapy Through Cherenkov Light-Activated Phototherapy.
    (International journal of radiation oncology, biology, physics, 2018-03) Yoon, Suk W; Tsvankin, Vadim; Shrock, Zachary; Meng, Boyu; Zhang, Xiaofeng; Dewhirst, Mark; Fecci, Peter; Adamson, Justus; Oldham, Mark
    This work investigates a new approach to enhance radiotherapy through a photo therapeutic agent activated by Cherenkov light produced from the megavoltage photon beam. The process is termed Radiotherapy Enhanced with Cherenkov photo-Activation (RECA). RECA is compatible with various photo-therapeutics, but here we focus on use with psoralen, an ultraviolet activated therapeutic with extensive history of application in superficial and extracorporeal settings. RECA has potential to extend the scope of psoralen treatments beyond superficial to deep seated lesions.In vitro studies in B16 melanoma and 4T1 murine breast cancer cells were performed to investigate the potential of RT plus RECA versus RT alone for increasing cytotoxicity (local control) and increasing surface expression of major histocompatibility complex I (MHC I). The latter represents potential for immune response amplification (increased antigen presentation), which has been observed in other psoralen therapies. Cytotoxicity assays included luminescence and clonogenics. The MHC I assays were performed using flow cytometry. In addition, Cherenkov light intensity measurements were performed to investigate the possibility of increasing the Cherenkov light intensity per unit dose from clinical megavoltage beams, to maximize psoralen activation.Luminescence assays showed that RECA treatment (2 Gy at 6 MV) increased cytotoxicity by up to 20% and 9.5% for 4T1 and B16 cells, respectively, compared with radiation and psoralen alone (ie, Cherenkov light was blocked). Similarly, flow cytometry revealed median MHC I expression was significantly higher in RECA-treated cells, compared with those receiving radiation and psoralen alone (approximately 450% and 250% at 3 Gy and 6 Gy, respectively, P << .0001). Clonogenic assays of B16 cells at doses of 6 Gy and 12 Gy showed decreases in tumor cell viability of 7% (P = .017) and 36% (P = .006), respectively, when Cherenkov was present.This work demonstrates for the first time the potential for photo-activation of psoralen directly in situ, from Cherenkov light generated by a clinical megavoltage treatment beam.
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    Instrumentation in Diffuse Optical Imaging.
    (Photonics, 2014-03-20) Zhang, Xiaofeng
    Diffuse optical imaging is highly versatile and has a very broad range of applications in biology and medicine. It covers diffuse optical tomography, fluorescence diffuse optical tomography, bioluminescence, and a number of other new imaging methods. These methods of diffuse optical imaging have diversified instrument configurations but share the same core physical principle - light propagation in highly diffusive media, i.e., the biological tissue. In this review, the author summarizes the latest development in instrumentation and methodology available to diffuse optical imaging in terms of system architecture, light source, photo-detection, spectral separation, signal modulation, and lastly imaging contrast.
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    Noninvasive measurement of tissue blood oxygenation with Cerenkov imaging during therapeutic radiation delivery
    (Optics Letters, 2017-08-15) Zhang, Xiaofeng; Lam, Sai Kit; Palmer, Gregory; Das, Shiva; Oldham, Mark; Dewhirst, Mark
    © 2017 Optical Society of America. Tumor tissue oxygenation significantly affects the outcome of radiotherapy. Real-time monitoring of tumor hypoxia is highly desirable for effective radiotherapy, and is the basis for improved treatment because hypoxic tumor cells are more resistant to radiation damage than fully oxygenated cells. We propose to use Cerenkov imaging to monitor tumor hypoxia by means of tissue blood oxygenation without the need for any exogenous contrast agent. Using a rodent hypoxia model, we demonstrate that Cerenkov imaging can be used as a noninvasive and noncontact method to measure tissue blood oxygenation level during radiation delivery. The data from Cerenkov imaging were validated using near infrared spectrometry methods. The results demonstrate the feasibility of using Cerenkov imaging to monitor tumor hypoxia during therapeutic radiation delivery.
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    Super-resolution method for arbitrary retrospective sampling in fluorescence tomography with raster scanning photodetectors.
    (Proc SPIE Int Soc Opt Eng, 2013-03-22) Zhang, Xiaofeng
    Dense spatial sampling is required in high-resolution optical imaging and many other biomedical optical imaging methods, such as diffuse optical imaging. Arrayed photodetectors, in particular charge coupled device cameras are commonly used mainly because of their high pixel count. Nonetheless, discrete-element photodetectors, such as photomultiplier tubes, are often desirable in many performance-demanding imaging applications. However, utilization of the discrete-element photodetectors typically requires raster scan to achieve arbitrary retrospective sampling with high density. Care must be taken in using the relatively large sensitive areas of discrete-element photodetectors to densely sample the image plane. In addition, off-line data analysis and image reconstruction often require full-field sampling. Pixel-by-pixel scanning is not only slow but also unnecessary in diffusion-limited imaging. We propose a super-resolution method that can recover the finer features of an image sampled with a coarse-scale sensor. This generalpurpose method was established on the spatial transfer function of the photodetector-lens system, and achieved super-resolution by inversion of this linear transfer function. Regularized optimization algorithms were used to achieve optimized deconvolution. Compared to the uncorrected blurred image, the proposed super-resolution method significantly improved image quality in terms of resolution and quantitation. Using this reconstruction method, the acquisition speed with a scanning photodetector can be dramatically improved without significantly sacrificing sampling density or flexibility.
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    Time-Resolved Synchronous Fluorescence for Biomedical Diagnosis.
    (Sensors (Basel), 2015-08-31) Zhang, Xiaofeng; Fales, Andrew; Vo-Dinh, Tuan
    This article presents our most recent advances in synchronous fluorescence (SF) methodology for biomedical diagnostics. The SF method is characterized by simultaneously scanning both the excitation and emission wavelengths while keeping a constant wavelength interval between them. Compared to conventional fluorescence spectroscopy, the SF method simplifies the emission spectrum while enabling greater selectivity, and has been successfully used to detect subtle differences in the fluorescence emission signatures of biochemical species in cells and tissues. The SF method can be used in imaging to analyze dysplastic cells in vitro and tissue in vivo. Based on the SF method, here we demonstrate the feasibility of a time-resolved synchronous fluorescence (TRSF) method, which incorporates the intrinsic fluorescent decay characteristics of the fluorophores. Our prototype TRSF system has clearly shown its advantage in spectro-temporal separation of the fluorophores that were otherwise difficult to spectrally separate in SF spectroscopy. We envision that our previously-tested SF imaging and the newly-developed TRSF methods will combine their proven diagnostic potentials in cancer diagnosis to further improve the efficacy of SF-based biomedical diagnostics.