5 results
4081 Quantifying pH buffering capacity and kinetics of tumor and healthy tissue to understand and exploit differences in biology
- A. Colleen Crouch, Emily A. Thompson, Mark D. Pagel, Erik N.K. Cressman
-
- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 15
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/GOALS: The purpose of this work is to investigate natural buffering capacity of liver tissue and tumors, to understand and exploit differences for therapy. Using this work, we will determine the concentrations of reagents (acids or bases) used in ablation treatment to optimize treatment by increasing tumor toxicity and minimizing healthy tissue toxicity. METHODS/STUDY POPULATION: For this preliminary study, two methods will be used: benchtop pH experiments ex vivo and non-invasive imaging using acidoCEST MRI in vivo. For ex vivo, two types of tissues will be tested: non-cancerous liver and tumor tissue from HepG2 inoculated mice (n = 10). After mice are euthanized, pH will be measured in tissue homogenates at baseline and then the homogenates will be placed in either acidic (acetic acid) or basic (sodium hydroxide) solutions with varied concentrations (0.5–10M) and time recorded until pH returns to baseline. For in vivo imaging, Mia PaCA-2 flank model mice (n = 10) will be imaged with acidoCEST MRI to quantify pH at baseline. Mice will then be injected intratumorally with (up to 100 μL of) acid or base at increasing concentrations and imaged to quantify pH changes in the tumor. RESULTS/ANTICIPATED RESULTS: For this study, buffering capacity is defined as the concentration threshold for which tissue can buffer pH back to within normal range. Non-cancerous tissue is likely to buffer a wider range of concentrations compared to tumor tissue. From the benchtop experiment, comparison of time-to-buffer will be made for each concentration of acid/base for the two tissue types. AcidoCEST MRI will provide in vivo buffering capacity and potentially demonstrate tumor heterogeneity of buffering capacity. For both experiments, a pH vs. concentration curve for the two tissue types will allow for comparison of ex vivo to in vivo experiments, which will differentiate contributions of local tissue buffering capacity from the full body’s natural bicarbonate buffer system that depends on respiration and blood flow. DISCUSSION/SIGNIFICANCE OF IMPACT: The pH of the body must be maintained within a narrow range. With cancer, impairment in regulation of tumor metabolism causes acidosis, lowering extracellular pH in tumors. It remains unclear if pH plays a role in local recurrence or tumor toxicity. This work will determine if acidoCEST MRI can measure deliberate alteration of pH and how this change affects biology.
Contributors
-
- By Waiel Almoustadi, Brian J. Anderson, David B. Auyong, Michael Avidan, Michael J. Avram, Roland J. Bainton, Jeffrey R. Balser, Juliana Barr, W. Scott Beattie, Manfred Blobner, T. Andrew Bowdle, Walter A. Boyle, Eugene B. Campbell, Laura F. Cavallone, Mario Cibelli, C. Michael Crowder, Ola Dale, M. Frances Davies, Mark Dershwitz, George Despotis, Clifford S. Deutschman, Brian S. Donahue, Marcel E. Durieux, Thomas J. Ebert, Talmage D. Egan, Helge Eilers, E. Wesley Ely, Charles W. Emala, Alex S. Evers, Heidrun Fink, Pierre Foëx, Stuart A. Forman, Helen F. Galley, Josephine M. Garcia-Ferrer, Robert W. Gereau, Tony Gin, David Glick, B. Joseph Guglielmo, Dhanesh K. Gupta, Howard B. Gutstein, Robert G. Hahn, Greg B. Hammer, Brian P. Head, Helen Higham, Laureen Hill, Kirk Hogan, Charles W. Hogue, Christopher G. Hughes, Eric Jacobsohn, Roger A. Johns, Dean R. Jones, Max Kelz, Evan D. Kharasch, Ellen W. King, W. Andrew Kofke, Tom C. Krejcie, Richard M. Langford, H. T. Lee, Isobel Lever, Jerrold H. Levy, J. Lance Lichtor, Larry Lindenbaum, Hung Pin Liu, Geoff Lockwood, Alex Macario, Conan MacDougall, M. B. MacIver, Aman Mahajan, Nándor Marczin, J. A. Jeevendra Martyn, George A. Mashour, Mervyn Maze, Thomas McDowell, Stuart McGrane, Berend Mets, Patrick Meybohm, Charles F. Minto, Jonathan Moss, Mohamed Naguib, Istvan Nagy, Nick Oliver, Paul S. Pagel, Pratik P. Pandharipande, Piyush Patel, Andrew J. Patterson, Robert A. Pearce, Ronald G. Pearl, Misha Perouansky, Kristof Racz, Chinniampalayam Rajamohan, Nilesh Randive, Imre Redai, Stephen Robinson, Richard W. Rosenquist, Carl E. Rosow, Uwe Rudolph, Francis V. Salinas, Robert D. Sanders, Sunita Sastry, Michael Schäfer, Jens Scholz, Thomas W. Schnider, Mark A. Schumacher, John W. Sear, Frédérique S. Servin, Jeffrey H. Silverstein, Tom De Smet, Martin Smith, Joe Henry Steinbach, Markus Steinfath, David F. Stowe, Gary R. Strichartz, Michel M. R. F. Struys, Isao Tsuneyoshi, Robert A. Veselis, Arthur Wallace, Robert P. Walt, David C. Warltier, Nigel R. Webster, Jeanine Wiener-Kronish, Troy Wildes, Paul Wischmeyer, Ling-Gang Wu, Stephen Yang
- Edited by Alex S. Evers, Washington University School of Medicine, St Louis, Mervyn Maze, University of California, San Francisco, Evan D. Kharasch, Washington University School of Medicine, St Louis
-
- Book:
- Anesthetic Pharmacology
- Published online:
- 11 April 2011
- Print publication:
- 10 March 2011, pp viii-xiv
-
- Chapter
- Export citation
4 - Noninvasive Imaging of Gene Expression with Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy
- Sanjiv Sam Gambhir, Stanford University School of Medicine, California, Shahriar S. Yaghoubi, Stanford University School of Medicine, California
-
- Book:
- Molecular Imaging with Reporter Genes
- Published online:
- 07 September 2010
- Print publication:
- 31 May 2010, pp 88-110
-
- Chapter
- Export citation
-
Summary
INTRODUCTION
Magnetic resonance imaging (MRI) has developed from an intriguing research project initially conceived in 1973 to an essential diagnostic method in the armamentarium of clinical radiologists. An estimated 26.6 million MRI procedures were performed in 2006 in the United States that generated approximately $20 billion in service revenue. The demand for clinical MRI diagnoses is expected to increase by 30% by 2020. This projected growth is due in part to the rising prevalence of age-related pathologies of soft tissues that can be conveniently monitored with MRI, such as the anatomy of pathologies in the cardiopulmonary system (e.g., regions of myocardial infarcts), neurological system (e.g., regions of cerebral infarcts, morphological changes during multiple sclerosis), and musculoskeletal system (e.g., tears in ligaments, tendons, and cartilage). MRI offers advantages relative to optical imaging methods limited to making diagnoses only near tissue surfaces, and relative to PET, SPECT, CT, and X-ray imaging methods that use potentially harmful ionizing radiation. Unlike these other imaging modalities, MRI also provides excellent spatial resolution at or smaller than 1 mm3 for clinical diagnostics and approaching 0.1 mm3 for small-animal research studies. MRI can also assess physiological function, such as the function of the cardiopulmonary system (e.g., MR angiography of vasculature), neurological system (e.g., fMRI of brain activity), renal system (e.g., perfusion imaging of kidney function), musculoskeletal system (e.g., MR elastography of connective tissues), and cancer lesions (e.g., dynamic contrast enhancement MRI of angiogenic tumors).
Rogues' Gallery of Contributing Authors
-
- By Ramon Abola, Rishimani Adsumelli, Syed Azim, Tazeen Beg, Helene Benveniste, Louis Chun, Ramtin Cohanim, Dominick Coleman, Joseph Conrad, Tommy Corrado, Jason Daras, Michelle DiGuglielmo, Vedan Djesevic, Andrew Drollinger, Kathleen Dubrow, Brian Durkin, Ralph Epstein, Christopher J. Gallagher, Xiaojun Guo, Sofie Hussain, Ron Jasiewicz, Anna Kogan, Ursula Landman, Rany Makaryus, Daryn Moller, Tate Montgomery, Matthew Neal, Khoa Nguyen, Marco Palmieri, Shaji Poovathor, Eric Posner, Deborah Richman, Andrew Rozbruch, Misako Sakamaki, Joy Schabel, Bharathi Scott, Peggy Seidman, Shiena Sharma, Vishal Sharma, Ellen Steinberg, Neera Tewari, Jane Yi, Jonida Zeqo, Peter Chung, John Denny, Steven H. Ginsberg, Jeremy Grayson, Jonathan Kraidin, Stephen Lemke, Tejal Patel, Salvatore Zisa, Charles Cowles, Marc Rozner, Shawn Banks, Deborah Brauer, Lebron Cooper, V. Samepathi David, Steve Gayer, Steven Gil, Eric A. Harris, Murlikrishna Kannan, Michael C. Lewis, David A. Lindley, Carlos M. Mijares, Sana Nini, Shafeena Nurani, Sujatha Pentakota, Edgar Pierre, Amy Klash Pulido, Michael Rossi, Miguel Santos, Nancy Setzer-Saade, Adam Sewell, Omair H. Toor, Ashish Udeshi, Patricia Wawroski, Lauren C. Berkow, Dan Berkowitz, Ramola Bhambhani, Kerry K. Blaha, Veronica Busso, Adam J. Carinci, Paul J. Christo, R. Blaine Easley, Ralph J. Fuchs, Samuel M. Galvagno, Nishant Gandhi, Andrew Goins, Robert S. Greenberg, Sayeh Hamzehzadeh, Theresa L. Hartsell, Eugenie Heitmiller, Jeremy M. Huff, Brijen L. Joshi, Sapna Kudchadkar, Jennifer K. Lee, Ira Lehrer, Peter Lin, Justin Lockman, Christine L. Mai, Christina Miller, Nanhi Mitter, Gillian Newman, Daniel Nyhan, Lale Odekon, Rabi Panigrahi, Melissa Pant, Alexander Papangelou, Mark Rossberg, Adam Schiavi, Steven J. Schwartz, Deborah A. Schwengel, Brandon M. Togioka, Tina Tran, Emmett Whitaker, Bradford D. Winters, Christopher Wu, Elena J. Holak, Paul S. Pagel
- Edited by Christopher J. Gallagher, State University of New York, Stony Brook, Michael C. Lewis, University of Miami School of Medicine, Deborah A. Schwengel
-
- Book:
- Core Clinical Competencies in Anesthesiology
- Published online:
- 06 July 2010
- Print publication:
- 12 April 2010, pp xi-xii
-
- Chapter
- Export citation
The potential for genetic adaptations to language
- Mark Pagel, Quentin D. Atkinson
-
- Journal:
- Behavioral and Brain Sciences / Volume 31 / Issue 5 / October 2008
- Published online by Cambridge University Press:
- 01 October 2008, pp. 529-530
-
- Article
- Export citation
-
We suggest there is somewhat more potential than Christiansen & Chater (C&C) allow for genetic adaptations specific to language. Our uniquely cooperative social system requires sophisticated language skills. Learning and performance of some culturally transmitted elements in animals is genetically based, and we give examples of features of human language that evolve slowly enough that genetic adaptations to them may arise.