The Experts below are selected from a list of 7575 Experts worldwide ranked by ideXlab platform
Bruce J Tromberg - One of the best experts on this subject based on the ideXlab platform.
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frequent optical imaging during breast cancer neoadjuvant chemotherapy reveals dynamic Tumor Physiology in an individual patient
Academic Radiology, 2010Co-Authors: Albert E Cerussi, Vaya W Tanamai, Rita S Mehta, David Hsiang, John Butler, Bruce J TrombergAbstract:Rationale and Objectives Imaging Tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about Tumor response dynamics may be missed. In addition, current clinical standards are based on determining Tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier-to-access bedside approach that can be used for frequent, functional assessment of dynamic Tumor Physiology in individual patients. Materials and Methods Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in Tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial Tumor size 60 × 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period. Results A composite index, the Tissue Optical Index (TOI), showed a significant (∼50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic Tumor Physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery. Conclusion This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy.
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monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy a case study
Journal of Biomedical Optics, 2004Co-Authors: Dorota Jakubowski, Albert E Cerussi, David Hsiang, John Butler, Frederic Bevilacqua, Natasha Shah, Bruce J TrombergAbstract:Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninva- sive, near-infrared method based on diffuse optical spectroscopy (DOS) to quantitatively monitor Tumor response to neoadjuvant che- motherapy. DOS was used to monitor Tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin- cyclophosphamide therapy and at several time points over the course of three treatment cycles (68 days). Our results show strong Tumor to normal (T/N) tissue contrast in total hemoglobin concentration (T/N =2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation, StO2 (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline (T/N 50.9) while StO2 exceeded pretreatment levels (T/N =1.5). Approxi- mately half of the hemoglobin and water changes occurred within 5 days of treatment (26 and 37%, respectively). These data suggest that noninvasive, quantitative optical methods that characterize Tumor Physiology may be useful in assessing and optimizing individual re- sponse to neoadjuvant chemotherapy. © 2004 Society of Photo-Optical Instru-
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monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy a case study
Journal of Biomedical Optics, 2004Co-Authors: Dorota Jakubowski, Albert E Cerussi, David Hsiang, John Butler, Frederic Bevilacqua, Natasha Shah, Bruce J TrombergAbstract:Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninvasive, near-infrared method based on diffuse optical spectroscopy (DOS) to quantitatively monitor Tumor response to neoadjuvant chemotherapy. DOS was used to monitor Tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin-cyclophosphamide therapy and at several time points over the course of three treatment cycles (68 days). Our results show strong Tumor to normal (T/N) tissue contrast in total hemoglobin concentration (T/N=2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation, S(t)O(2) (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline (T/N =0.9) while S(t)O(2) exceeded pretreatment levels (T/N =1.5). Approximately half of the hemoglobin and water changes occurred within 5 days of treatment (26 and 37%, respectively). These data suggest that noninvasive, quantitative optical methods that characterize Tumor Physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy.
Murali C Krishna - One of the best experts on this subject based on the ideXlab platform.
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pulsed electron paramagnetic resonance imaging applications in the studies of Tumor Physiology
Antioxidants & Redox Signaling, 2018Co-Authors: Shun Kishimoto, Kenichiro Matsumoto, Keita Saito, Ayano Enomoto, Shingo Matsumoto, James B Mitchell, Nallathamby Devasahayam, Murali C KrishnaAbstract:Abstract Significance: Electron paramagnetic resonance imaging (EPRI) is capable of generating images of tissue oxygenation using exogenous paramagnetic probes such as trityl radicals or nitroxyl radicals. The spatial distribution of the paramagnetic probe can be generated using magnetic field gradients as in magnetic resonance imaging and, from its spectral features, spatial maps of oxygen can be obtained from live objects. In this review, two methods of signal acquisition and image formation/reconstruction are described. The probes used and its application to study Tumor Physiology and monitor treatment response with chemotherapy drugs in mouse models of human cancer are summarized. Recent Advances: By implementing phase encoding/Fourier reconstruction in EPRI in time domain mode, the frequency contribution to the spatial resolution was avoided and images with improved spatial resolution were obtained. The EPRI-generated pO2 maps in Tumor were useful to detect and evaluate the effects of various antitum...
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overhauser enhanced magnetic resonance imaging for Tumor oximetry coregistration of Tumor anatomy and tissue oxygen concentration
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Murali C Krishna, Nallathamby Devasahayam, Sean J English, Kenichi Yamada, John Yoo, Ramachandran Murugesan, John A Cook, Klaes Golman, Jan Henrik Ardenkjaerlarsen, S SubramanianAbstract:An efficient noninvasive method for in vivo imaging of Tumor oxygenation by using a low-field magnetic resonance scanner and a paramagnetic contrast agent is described. The methodology is based on Overhauser enhanced magnetic resonance imaging (OMRI), a functional imaging technique. OMRI experiments were performed on Tumor-bearing mice (squamous cell carcinoma) by i.v. administration of the contrast agent Oxo63 (a highly derivatized triarylmethyl radical) at nontoxic doses in the range of 2–7 mmol/kg either as a bolus or as a continuous infusion. Spatially resolved pO2 (oxygen concentration) images from OMRI experiments of Tumor-bearing mice exhibited heterogeneous oxygenation profiles and revealed regions of hypoxia in Tumors (<10 mmHg; 1 mmHg = 133 Pa). Oxygenation of Tumors was enhanced on carbogen (95% O2/5% CO2) inhalation. The pO2 measurements from OMRI were found to be in agreement with those obtained by independent polarographic measurements using a pO2 Eppendorf electrode. This work illustrates that anatomically coregistered pO2 maps of Tumors can be readily obtained by combining the good anatomical resolution of water proton-based MRI, and the superior pO2 sensitivity of EPR. OMRI affords the opportunity to perform noninvasive and repeated pO2 measurements of the same animal with useful spatial (≈1 mm) and temporal (2 min) resolution, making this method a powerful imaging modality for small animal research to understand Tumor Physiology and potentially for human applications.
Mark W. Dewhirst - One of the best experts on this subject based on the ideXlab platform.
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non invasive monitoring of intra Tumor drug concentration and therapeutic response using optical spectroscopy
Journal of Controlled Release, 2010Co-Authors: Gregory M Palmer, Benjamin L Viglianti, Richard J Boruta, Lan Lan, Ivan Spasojevic, Mark W. DewhirstAbstract:Optical spectroscopy was used to monitor changes in Tumor Physiology with therapy, and its influence on drug delivery and treatment efficacy for hyperthermia treatment combined with free doxorubicin or a low-temperature sensitive liposomal formulation. Monte Carlo-based modeling techniques were used to characterize the intrinsic absorption, scattering, and fluorescence properties of tissue. Fluorescence assessment of drug concentration was validated against HPLC and found to be significantly linearly correlated (r=0.88). Cluster analysis on the physiologic data obtained by optical spectroscopy revealed two physiologic phenotypes prior to treatment. One of these was relatively hypoxic, with relatively low total hemoglobin content. This hypoxic group was found to have a significantly shorter time to reach 3 times pre-treatment volume, indicating a more treatment resistant phenotype (p=0.003). Influence of Tumor Physiology was assessed in more detail for the liposomal doxorubicin+hyperthermia group, which demonstrated a highly significant correlation between pre-treatment hemoglobin saturation and Tumor growth delay, and also between post-hyperthermia total hemoglobin content and Tumor drug delivery. Finally, it was found that the doxorubicin concentration, measured in vivo using fluorescence techniques significantly predicted for chemoresponse (hazard ratio: 0.34, p=0.0007). The ability to characterize drug delivery and Tumor Physiology in vivo makes this a potentially useful tool for evaluating the efficacy of targeted delivery systems in preclinical studies, and may be translatable for monitoring and predicting individual treatment responses in the clinic.
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quantitative diffuse reflectance and fluorescence spectroscopy tool to monitor Tumor Physiology in vivo
Journal of Biomedical Optics, 2009Co-Authors: Gregory M Palmer, Mark W. Dewhirst, Ronald J Viola, Thies Schroeder, Pavel S Yarmolenko, Nirmala RamanujamAbstract:This study demonstrates the use of optical spectroscopy for monitoring Tumor oxygenation and metabolism in response to hyperoxic gas breathing. Hemoglobin saturation and redox ratio were quantified for a set of 14 and 9 mice, respectively, measured at baseline and during carbogen breathing (95% O2, 5% CO2). In particular, significant increases in hemoglobin saturation and fluorescence redox ratio were observed upon carbogen breathing. These data were compared with data obtained concurrently using an established invasive technique, the OxyLite partial oxygen pressure (pO2) system, which also showed a significant increase in pO2. It was found that the direction of changes were generally the same between all of the methods, but that the OxyLite system was much more variable in general, suggesting that optical techniques may provide a better assessment of global Tumor Physiology. Optical spectroscopy measurements are demonstrated to provide a reliable, reproducible indication of changes in Tumor Physiology in response to physiologic manipulation.
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longitudinal monitoring of 4t1 Tumor Physiology in vivo with doxorubicin treatment via diffuse optical spectroscopy
Biomedical optics, 2008Co-Authors: Karthik Vishwanath, Mark W. Dewhirst, Hong Yuan, Laura Moore, Janelle E Bender, Nimmi RamanujamAbstract:A diffuse optical spectrometer was used to monitor 4T1 breast carcinoma Tumors implanted in mice. Animals treated with doxorubicin showed relative increased oxygen saturation and decreased blood volume vs. controls, over a 10 day period.
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Tumor Physiology and cell kinetics.
Seminars in veterinary medicine and surgery (small animal), 1995Co-Authors: Mark W. Dewhirst, Susan M. Larue, Leo E. GerweckAbstract:The abnormal physiological state of Tumors has traditionally been thought to be a source of treatment resistance and altered metastatic phenotype. However, the recent recognition that this altered physiological state is unique to solid cancers gives some hope that Tumor selective therapeutic strategies could be developed that will specifically target these cells. Investigations into the development of drugs that specifically target acidotic and hypoxic cells could represent a significantly selective adjuvant therapy to be used in combination with more traditional forms of treatment. Newer forms of targeted therapy will rely on delivery of directed antibodies, growth factor receptor ligands, or gene therapy, delivered via immune cells or viruses. Unfortunately, physiological barriers exist in Tumors that will impede the success of such strategies no matter how specific they are. Methods to ameliorate high interstitial pressures and defects in adhesion molecule function are needed to circumvent these barriers. Current methods of evaluating Tumor cell kinetics provide data quickly, so this information could impact treatment decisions. Kinetic parameters are proving to be useful tools in selecting patient subpopulations that may respond better to altered treatment regimens. Studies in spontaneous rodent and xenografted human Tumors have shown that the number of clonogens per Tumor and their intrinsic sensitivity to radiation are major determinants of radiation Tumor control dose.
Chee M Ng - One of the best experts on this subject based on the ideXlab platform.
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gpu accelerated compartmental modeling analysis of dce mri data from glioblastoma patients treated with bevacizumab
PLOS ONE, 2015Co-Authors: Ziyin Huang, Gregory Z Ferl, Chee M NgAbstract:The compartment model analysis using medical imaging data is the well-established but extremely time consuming technique for quantifying the changes in microvascular Physiology of targeted organs in clinical patients after antivascular therapies. In this paper, we present a first graphics processing unit-accelerated method for compartmental modeling of medical imaging data. Using this approach, we performed the analysis of dynamic contrast-enhanced magnetic resonance imaging data from bevacizumab-treated glioblastoma patients in less than one minute per slice without losing accuracy. This approach reduced the computation time by more than 120-fold comparing to a central processing unit-based method that performed the analogous analysis steps in serial and more than 17-fold comparing to the algorithm that optimized for central processing unit computation. The method developed in this study could be of significant utility in reducing the computational times required to assess Tumor Physiology from dynamic contrast-enhanced magnetic resonance imaging data in preclinical and clinical development of antivascular therapies and related fields.
Robert J Griffin - One of the best experts on this subject based on the ideXlab platform.
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blood outgrowth endothelial cells increase Tumor growth rates and modify Tumor Physiology relevance for therapeutic targeting
Cancers, 2013Co-Authors: Jonathan Pagan, Azemat Jamshidiparsian, Beata Przybyla, Kalpna Gupta, Robert J GriffinAbstract:Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist Tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on Tumor growth and Physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into Tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung Tumors (i.e., less than 150 mm3) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger Tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF Tumors of animals injected with BOECs compared to control Tumors. In addition, FSaII murine fibrosarcoma Tumors were found to grow faster upon injection of BOECs. When FSaII Tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the Tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII Tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to Tumor vessel growth, Tumor progression and/or repair of Tumor damage and may improve the oxygenation and subsequent radiation response of Tumors. We surmise that these cells are preferentially stimulated to divide in the Tumor microenvironment, thereby inducing the significant increase in Tumor growth observed and that the use of injected BOECs could be a viable approach to modulate the Tumor microenvironment for therapeutic gain. Conversely, agents or approaches to block their recruitment and integration of BOECs into primary or metastatic lesions may be an effective way to restrain cancer progression before or after other treatments are applied.
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mild temperature hyperthermia and radiation therapy role of tumour vascular thermotolerance and relevant physiological factors
International Journal of Hyperthermia, 2010Co-Authors: Robert J Griffin, Ruud P M Dings, Azemat Jamshidiparsian, Chang W SongAbstract:Here we review the significance of changes in vascular thermotolerance on Tumor Physiology and the effects of multiple mild temperature hyperthermia (MTH) treatments on Tumor oxygenation and corresponding radiation response. New information suggests that although hyperthermia is a powerful modifier of Tumor blood flow and oxygenation, sequencing and frequency are central parameters in the success of MTH enhancement of radiation therapy. We hypothesize that heat treatments every 2–3 days combined with traditional or accelerated radiation fractionation may be maximally effective in exploiting the improved perfusion and oxygenation induced by typical thermal doses given in the clinic.
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scheduling of radiation with angiogenesis inhibitors anginex and avastin improves therapeutic outcome via vessel normalization
Clinical Cancer Research, 2007Co-Authors: Ruud P M Dings, Melissa Loren, Hanke Heun, Elizabeth A Mcniel, Arjan W Griffioen, Kevin H Mayo, Robert J GriffinAbstract:Purpose: To test whether a direct antiangiogenic peptide (anginex) and a vascular endothelial growth factor antibody (bevacizumab, Avastin) can transiently normalize vasculature within Tumors to improve oxygen delivery, alleviate hypoxia, and increase the effect of radiation therapy. Experimental Design: Tumor oxygenation levels, microvessel density and pericyte coverage were monitored in three different solid Tumor models (xenograft human ovarian carcinoma MA148, murine melanoma B16F10, and murine breast carcinoma SCK) in mice. Multiple treatment schedules were tested in these models to assess the influence on the effect of radiation therapy. Results: In all three Tumor models, we found that Tumor oxygenation levels, monitored daily in real time, were increased during the first 4 days of treatment with both anginex and bevacizumab. From treatment day 5 onward, Tumor oxygenation in treated mice decreased significantly to below that in control mice. This “Tumor oxygenation window” occurred in all three Tumor models varying in origin and growth rate. Moreover, during the treatment period, Tumor microvessel density decreased and pericyte coverage of vessels increased, supporting the idea of vessel normalization. We also found that the transient modulation of Tumor Physiology caused by either antiangiogenic therapy improved the effect of radiation treatment. Tumor growth delay was enhanced when single dose or fractionated radiotherapy was initiated within the Tumor oxygenation window as compared with other treatment schedules. Conclusions: The results are of immediate translational importance because the clinical benefits of bevacizumab therapy might be increased by more precise treatment scheduling to ensure radiation is given during periods of peak radiosensitivity. The oxygen elevation in Tumors by non–growth factor–mediated peptide anginex suggests that vessel normalization might be a general phenomenon of agents directed at disrupting the Tumor vasculature by a variety of mechanisms.
