36 results on '"Ramirez, Marc S."'
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2. Supplementary Video from Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors
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Bankson, James A., primary, Walker, Christopher M., primary, Ramirez, Marc S., primary, Stefan, Wolfgang, primary, Fuentes, David, primary, Merritt, Matthew E., primary, Lee, Jaehyuk, primary, Sandulache, Vlad C., primary, Chen, Yunyun, primary, Phan, Liem, primary, Chou, Ping-Chieh, primary, Rao, Arvind, primary, Yeung, Sai-Ching J., primary, Lee, Mong-Hong, primary, Schellingerhout, Dawid, primary, Conrad, Charles A., primary, Malloy, Craig, primary, Sherry, A. Dean, primary, Lai, Stephen Y., primary, and Hazle, John D., primary
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- 2023
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3. Supplemental Figures 1-6 from Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models
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Benito, Juliana, primary, Ramirez, Marc S., primary, Millward, Niki Zacharias, primary, Velez, Juliana, primary, Harutyunyan, Karine G., primary, Lu, Hongbo, primary, Shi, Yue-xi, primary, Matre, Polina, primary, Jacamo, Rodrigo, primary, Ma, Helen, primary, Konoplev, Sergej, primary, McQueen, Teresa, primary, Volgin, Andrei, primary, Protopopova, Marina, primary, Mu, Hong, primary, Lee, Jaehyuk, primary, Bhattacharya, Pratip K., primary, Marszalek, Joseph R., primary, Davis, R. Eric, primary, Bankson, James A., primary, Cortes, Jorge E., primary, Hart, Charles P., primary, Andreeff, Michael, primary, and Konopleva, Marina, primary
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- 2023
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4. Supplementary Table from Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors
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Bankson, James A., primary, Walker, Christopher M., primary, Ramirez, Marc S., primary, Stefan, Wolfgang, primary, Fuentes, David, primary, Merritt, Matthew E., primary, Lee, Jaehyuk, primary, Sandulache, Vlad C., primary, Chen, Yunyun, primary, Phan, Liem, primary, Chou, Ping-Chieh, primary, Rao, Arvind, primary, Yeung, Sai-Ching J., primary, Lee, Mong-Hong, primary, Schellingerhout, Dawid, primary, Conrad, Charles A., primary, Malloy, Craig, primary, Sherry, A. Dean, primary, Lai, Stephen Y., primary, and Hazle, John D., primary
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- 2023
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5. Data from Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors
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Bankson, James A., primary, Walker, Christopher M., primary, Ramirez, Marc S., primary, Stefan, Wolfgang, primary, Fuentes, David, primary, Merritt, Matthew E., primary, Lee, Jaehyuk, primary, Sandulache, Vlad C., primary, Chen, Yunyun, primary, Phan, Liem, primary, Chou, Ping-Chieh, primary, Rao, Arvind, primary, Yeung, Sai-Ching J., primary, Lee, Mong-Hong, primary, Schellingerhout, Dawid, primary, Conrad, Charles A., primary, Malloy, Craig, primary, Sherry, A. Dean, primary, Lai, Stephen Y., primary, and Hazle, John D., primary
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- 2023
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6. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo
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Venkatanarayan, Avinashnarayan, Raulji, Payal, Norton, William, Chakravarti, Deepavali, Coarfa, Cristian, Su, Xiaohua, Sandur, Santosh K., Ramirez, Marc S., Lee, Jaehuk, Kingsley, Charles V., Sananikone, Eliot F., Rajapakshe, Kimal, Naff, Katherine, Parker-Thornburg, Jan, Bankson, James A., Tsai, Kenneth Y., Gunaratne, Preethi H., and Flores, Elsa R.
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Metabolism -- Health aspects ,Tumor proteins -- Physiological aspects ,Polypeptides -- Usage -- Health aspects ,Cancer -- Care and treatment ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
p53 is often mutated or lost in cancer; here inactivation of [DELTA]Np63 and [DELTA]Np73 in the absence of p53 is shown to result in metabolic reprogramming and tumour regression via activation of IAPP (islet amyloid polypeptide or amylin), and IAPP-based anti-diabetes therapeutic strategies show potential for the treatment of p53-deficient and mutant tumours. A novel approach to targeting p53 cancers The tumour suppressor p53 is often mutated or lost in cancer. There is evidence from mouse models that reactivation of p53 activity in tumours can result in regression, but direct reactivation of normal p53 activity has not developed into an effective strategy for treating human cancer. In this paper Elsa Flores and colleagues show in mice that inactivation of the p53 family proteins p63 and p73, in the absence of p53, results in metabolic reprogramming and tumour regression through the activation of IAPP (islet amyloid polypeptide, also known as amylin). The anti-diabetic drug pramlintide, an amylin analogue, caused tumour regression in mice with p53-deficient thymic lymphomas, suggesting a novel strategy that might be used to target p53-deficient cancers. TP53 is commonly altered in human cancer, and Tp53 reactivation suppresses tumours in vivo in mice.sup.1,2 (TP53 and Tp53 are also known as p53). This strategy has proven difficult to implement therapeutically, and here we examine an alternative strategy by manipulating the p53 family members, Tp63 and Tp73 (also known as p63 and p73, respectively). The acidic transactivation-domain-bearing (TA) isoforms of p63 and p73 structurally and functionally resemble p53, whereas the [DELTA]N isoforms (lacking the acidic transactivation domain) of p63 and p73 are frequently overexpressed in cancer and act primarily in a dominant-negative fashion against p53, TAp63 and TAp73 to inhibit their tumour-suppressive functions.sup.3,4,5,6,7,8. The p53 family interacts extensively in cellular processes that promote tumour suppression, such as apoptosis and autophagy.sup.9,10,11,12,13,14, thus a clear understanding of this interplay in cancer is needed to treat tumours with alterations in the p53 pathway. Here we show that deletion of the [DELTA]N isoforms of p63 or p73 leads to metabolic reprogramming and regression of p53-deficient tumours through upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid peptide co-secreted with insulin by the [beta] cells of the pancreas. We found that IAPP is causally involved in this tumour regression and that amylin functions through the calcitonin receptor (CalcR) and receptor activity modifying protein 3 (RAMP3) to inhibit glycolysis and induce reactive oxygen species and apoptosis. Pramlintide, a synthetic analogue of amylin that is currently used to treat type 1 and type 2 diabetes, caused rapid tumour regression in p53-deficient thymic lymphomas, representing a novel strategy to target p53-deficient cancers., Author(s): Avinashnarayan Venkatanarayan [sup.1] [sup.2] [sup.3] [sup.4] , Payal Raulji [sup.1] [sup.2] , William Norton [sup.5] , Deepavali Chakravarti [sup.1] [sup.2] [sup.3] [sup.4] , Cristian Coarfa [sup.6] , Xiaohua Su [...]
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- 2015
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7. Feasibility of multianimal hyperpolarized 13C MRS
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Ramirez, Marc S., Lee, Jaehyuk, Walker, Christopher M., Chen, Yunyun, Kingsley, Charles V., De La Cerda, Jorge, Maldonado, Kiersten L., Lai, Stephen Y., and Bankson, James A.
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- 2015
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8. Radial spectroscopic MRI of hyperpolarized [1-13C] pyruvate at 7 tesla
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Ramirez, Marc S., Lee, Jaehyuk, Walker, Christopher M., Sandulache, Vlad C., Hennel, Franciszek, Lai, Stephen Y., and Bankson, James A.
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- 2014
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9. Multiple-Mouse MRI with Multiple Arrays of Receive Coils
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Ramirez, Marc S., Esparza-Coss, Emilio, and Bankson, James A.
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- 2010
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10. A Practical Method for 2D Multiple-Animal MRI
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Ramirez, Marc S. and Bankson, James A.
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- 2007
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11. High-throughput hyperpolarized 13C metabolic investigations using a multi-channel acquisition system
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Lee, Jaehyuk, Ramirez, Marc S., Walker, Christopher M., Chen, Yunyun, Yi, Stacey, Sandulache, Vlad C., Lai, Stephen Y., and Bankson, James A.
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- 2015
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12. Allele-specific reprogramming of cancer metabolism by the long non-coding RNA CCAT2
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Mohamed bin Zayed Species Conservation Fund, University of Texas, Fundações de Amparo à Pesquisa (Brasil), Leukemia & Lymphoma Society (US), National Institutes of Health (US), Redis, Roxana S., Vela, Luz E., Lu, Weiqin, Ferreira de Oliveira, Juliana, Rodriguez-Aguayo, Cristian, Adamoski, Douglas, Pasculli, Barbara, Taguchi, Ayumu, Chen, Yunyun, Fernández, Agustín F., Valledor, Luis, Van Roosbroeck, Katrien, Chang, Samuel, Shah, Maitri, Kinnebrew, Garrett, Han, Leng, Atlasi, Yaser, Cheung, Lawrence H., Huang, Gilbert Y., Monroig, Paloma, Ramirez, Marc S., Catela, Ivkovic, Tina, Van, Long, Ling, Hui, Gafà, Roberta, Kapitanovic, Sanja, Lanza, Giovanni, Bankson, James A., Huang, Peng, Lai, Stephen Y., Bast, Robert C., Rosenblum, Michael G., Radovich, Milan, Ivan, Mircea, Bartholomeusz, Geoffrey, Liang, Hang, Fraga, Mario F., Widger, William R., Hanash, Samir, Berindan-Neagoe, Ioana, Lopez-Berestein, Gabriel, Ambrosio, Andre L. B., Gomes Dias, Sandra M., Calin, George A., Mohamed bin Zayed Species Conservation Fund, University of Texas, Fundações de Amparo à Pesquisa (Brasil), Leukemia & Lymphoma Society (US), National Institutes of Health (US), Redis, Roxana S., Vela, Luz E., Lu, Weiqin, Ferreira de Oliveira, Juliana, Rodriguez-Aguayo, Cristian, Adamoski, Douglas, Pasculli, Barbara, Taguchi, Ayumu, Chen, Yunyun, Fernández, Agustín F., Valledor, Luis, Van Roosbroeck, Katrien, Chang, Samuel, Shah, Maitri, Kinnebrew, Garrett, Han, Leng, Atlasi, Yaser, Cheung, Lawrence H., Huang, Gilbert Y., Monroig, Paloma, Ramirez, Marc S., Catela, Ivkovic, Tina, Van, Long, Ling, Hui, Gafà, Roberta, Kapitanovic, Sanja, Lanza, Giovanni, Bankson, James A., Huang, Peng, Lai, Stephen Y., Bast, Robert C., Rosenblum, Michael G., Radovich, Milan, Ivan, Mircea, Bartholomeusz, Geoffrey, Liang, Hang, Fraga, Mario F., Widger, William R., Hanash, Samir, Berindan-Neagoe, Ioana, Lopez-Berestein, Gabriel, Ambrosio, Andre L. B., Gomes Dias, Sandra M., and Calin, George A.
- Abstract
Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine-tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele-specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA.
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- 2016
13. Radial Spectroscopic MRI of Hyperpolarized [1-13C]Pyruvate at 7 T
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Ramirez, Marc S., Lee, Jaehyuk, Walker, Christopher M., Sandulache, Vlad C., Hennel, Franciszek, Lai, Stephen Y., and Bankson, James A.
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Carbon Isotopes ,Electron Spin Resonance Spectroscopy ,Mice, Nude ,Reproducibility of Results ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Article ,Mice ,Pyruvic Acid ,Biomarkers, Tumor ,Animals ,Feasibility Studies ,Tissue Distribution ,Thyroid Neoplasms ,Radiopharmaceuticals ,Algorithms - Abstract
The transient and nonrenewable signal from hyperpolarized metabolites necessitates extensive sequence optimization for encoding spatial, spectral, and dynamic information. In this work, we evaluate the utility of radial single-timepoint and cumulative spectroscopic MRI of hyperpolarized [1-(13) C] pyruvate and its metabolic products at 7 Tesla (T).Simulations of radial echo planar spectroscopic imaging (EPSI) and multiband frequency encoding (MBFE) acquisitions were performed to confirm feasibility and evaluate performance for HP (13) C imaging. Corresponding sequences were implemented on a 7T small-animal MRI system, tested in phantom, and demonstrated in a murine model of anaplastic thyroid cancer.MBFE provides excellent spectral separation but is susceptible to blurring and T2 * signal loss inherent to using low readout gradients. The higher readout gradients and more flexible spectral encoding for EPSI result in good spatial resolution and spectral separation. Radial acquisition throughout HP signal evolution offers the flexibility for reconstructing spatial maps of mean metabolite distribution and global dynamic time courses of multiple metabolites.Radial EPSI and MBFE acquisitions are well-suited for hyperpolarized (13) C MRI over short and long durations. Advantages to this approach include robustness to nonstationary magnetization, insensitivity to precise acquisition timing, and versatility for reconstructing dynamically acquired spectroscopic data.
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- 2013
14. Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models
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Benito, Juliana, primary, Ramirez, Marc S., additional, Millward, Niki Zacharias, additional, Velez, Juliana, additional, Harutyunyan, Karine G., additional, Lu, Hongbo, additional, Shi, Yue-xi, additional, Matre, Polina, additional, Jacamo, Rodrigo, additional, Ma, Helen, additional, Konoplev, Sergej, additional, McQueen, Teresa, additional, Volgin, Andrei, additional, Protopopova, Marina, additional, Mu, Hong, additional, Lee, Jaehyuk, additional, Bhattacharya, Pratip K., additional, Marszalek, Joseph R., additional, Davis, R. Eric, additional, Bankson, James A., additional, Cortes, Jorge E., additional, Hart, Charles P., additional, Andreeff, Michael, additional, and Konopleva, Marina, additional
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- 2016
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15. Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2
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Redis, Roxana S., primary, Vela, Luz E., additional, Lu, Weiqin, additional, Ferreira de Oliveira, Juliana, additional, Ivan, Cristina, additional, Rodriguez-Aguayo, Cristian, additional, Adamoski, Douglas, additional, Pasculli, Barbara, additional, Taguchi, Ayumu, additional, Chen, Yunyun, additional, Fernandez, Agustin F., additional, Valledor, Luis, additional, Van Roosbroeck, Katrien, additional, Chang, Samuel, additional, Shah, Maitri, additional, Kinnebrew, Garrett, additional, Han, Leng, additional, Atlasi, Yaser, additional, Cheung, Lawrence H., additional, Huang, Gilbert Y., additional, Monroig, Paloma, additional, Ramirez, Marc S., additional, Catela Ivkovic, Tina, additional, Van, Long, additional, Ling, Hui, additional, Gafà, Roberta, additional, Kapitanovic, Sanja, additional, Lanza, Giovanni, additional, Bankson, James A., additional, Huang, Peng, additional, Lai, Stephen Y., additional, Bast, Robert C., additional, Rosenblum, Michael G., additional, Radovich, Milan, additional, Ivan, Mircea, additional, Bartholomeusz, Geoffrey, additional, Liang, Han, additional, Fraga, Mario F., additional, Widger, William R., additional, Hanash, Samir, additional, Berindan-Neagoe, Ioana, additional, Lopez-Berestein, Gabriel, additional, Ambrosio, Andre L.B., additional, Gomes Dias, Sandra M., additional, and Calin, George A., additional
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- 2016
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- View/download PDF
16. Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors
- Author
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Bankson, James A., primary, Walker, Christopher M., additional, Ramirez, Marc S., additional, Stefan, Wolfgang, additional, Fuentes, David, additional, Merritt, Matthew E., additional, Lee, Jaehyuk, additional, Sandulache, Vlad C., additional, Chen, Yunyun, additional, Phan, Liem, additional, Chou, Ping-Chieh, additional, Rao, Arvind, additional, Yeung, Sai-Ching J., additional, Lee, Mong-Hong, additional, Schellingerhout, Dawid, additional, Conrad, Charles A., additional, Malloy, Craig, additional, Sherry, A. Dean, additional, Lai, Stephen Y., additional, and Hazle, John D., additional
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- 2015
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17. High-throughput hyperpolarized 13 C metabolic investigations using a multi-channel acquisition system
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Lee, Jaehyuk, primary, Ramirez, Marc S., additional, Walker, Christopher M., additional, Chen, Yunyun, additional, Yi, Stacey, additional, Sandulache, Vlad C., additional, Lai, Stephen Y., additional, and Bankson, James A., additional
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- 2015
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18. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo
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Venkatanarayan, Avinashnarayan, primary, Raulji, Payal, additional, Norton, William, additional, Chakravarti, Deepavali, additional, Coarfa, Cristian, additional, Su, Xiaohua, additional, Sandur, Santosh K., additional, Ramirez, Marc S., additional, Lee, Jaehuk, additional, Kingsley, Charles V., additional, Sananikone, Eliot F., additional, Rajapakshe, Kimal, additional, Naff, Katherine, additional, Parker-Thornburg, Jan, additional, Bankson, James A., additional, Tsai, Kenneth Y., additional, Gunaratne, Preethi H., additional, and Flores, Elsa R., additional
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- 2014
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19. Feasibility of multianimal hyperpolarized 13 C MRS
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Ramirez, Marc S., primary, Lee, Jaehyuk, additional, Walker, Christopher M., additional, Chen, Yunyun, additional, Kingsley, Charles V., additional, De La Cerda, Jorge, additional, Maldonado, Kiersten L., additional, Lai, Stephen Y., additional, and Bankson, James A., additional
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- 2014
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20. Evaluation of Hyperpolarized [1-13C]-Pyruvate by Magnetic Resonance to Detect Ionizing Radiation Effects in Real Time
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Sandulache, Vlad C., primary, Chen, Yunyun, additional, Lee, Jaehyuk, additional, Rubinstein, Ashley, additional, Ramirez, Marc S., additional, Skinner, Heath D., additional, Walker, Christopher M., additional, Williams, Michelle D., additional, Tailor, Ramesh, additional, Court, Laurence E., additional, Bankson, James A., additional, and Lai, Stephen Y., additional
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- 2014
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21. Radial spectroscopic MRI of hyperpolarized [1-13C] pyruvate at 7 tesla
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Ramirez, Marc S., primary, Lee, Jaehyuk, additional, Walker, Christopher M., additional, Sandulache, Vlad C., additional, Hennel, Franciszek, additional, Lai, Stephen Y., additional, and Bankson, James A., additional
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- 2013
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22. A Catalyzing Phantom for Reproducible Dynamic Conversion of Hyperpolarized [1-13C]-Pyruvate
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Walker, Christopher M., primary, Lee, Jaehyuk, additional, Ramirez, Marc S., additional, Schellingerhout, Dawid, additional, Millward, Steven, additional, and Bankson, James A., additional
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- 2013
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23. A throughput-optimized array system for multiple-mouse MRI
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Ramirez, Marc S., primary, Lai, Stephen Y., additional, and Bankson, James A., additional
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- 2012
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24. Monitoring Histone Deacetylase Inhibition In Vivo: Noninvasive Magnetic Resonance Spectroscopy Method
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Sankaranarayanapillai, Madhuri, primary, Tong, William P., additional, Yuan, Qing, additional, Bankson, James A., additional, Dafni, Hagit, additional, Bornmann, William G., additional, Soghomonyan, Suren, additional, Pal, Ashutosh, additional, Ramirez, Marc S., additional, Webb, Douglas, additional, Kaluarachchi, Kumaralal, additional, Gelovani, Juri G., additional, and Ronen, Sabrina M., additional
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- 2008
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25. Wireless self-gated multiple-mouse cardiac cine MRI
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Esparza-Coss, Emilio, primary, Ramirez, Marc S., additional, and Bankson, James A., additional
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- 2008
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26. Feasibility of multiple‐mouse dynamic contrast‐enhanced MRI
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Ramirez, Marc S., primary, Ragan, Dustin K., additional, Kundra, Vikas, additional, and Bankson, James A., additional
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- 2007
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27. Feasibility of multianimal hyperpolarized 13C MRS.
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Ramirez, Marc S., Lee, Jaehyuk, Walker, Christopher M., Chen, Yunyun, Kingsley, Charles V., Cerda, Jorge, Maldonado, Kiersten L., Lai, Stephen Y., and Bankson, James A.
- Abstract
Purpose There is great potential for real-time investigation of metabolism with MRS and hyperpolarized (HP)
13 C agents. Unfortunately, HP technology has high associated costs and efficiency limitations that may constrain in vivo studies involving many animals. To improve the throughput of preclinical investigations, we evaluate the feasibility of performing HP MRS on multiple animals simultaneously. Methods Simulations helped assess the viability of a dual-coil strategy for spatially localized multivolume MRS. A dual-mouse system was assembled and characterized with bench- and scanner-based experiments. Enzyme phantoms mixed with HP [1-13 C] pyruvate emulated real-time metabolism and offered a controlled mechanism for evaluating system performance. Finally, a normal mouse and a mouse bearing a subcutaneous xenograft of colon cancer were simultaneously scanned in vivo using an agent containing HP [1-13 C] pyruvate. Results Geometric separation/rotation, active decoupling, and use of low input impedance preamplifiers permitted an encode-by-channel approach for spatially localized MRS. A precalibrated shim allowed straightforward metabolite differentiation in enzyme phantom and in vivo experiments at 7 Tesla, with performance similar to conventional acquisitions. Conclusion The initial feasibility of multi-animal HP13 C MRS was established. Throughput scales with the number of simultaneously scanned animals, demonstrating the potential for significant improvements in study efficiency. Magn Reson Med 73:1726-1732, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2015
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28. Radial spectroscopic MRI of hyperpolarized [1-13C] pyruvate at 7 tesla.
- Author
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Ramirez, Marc S., Lee, Jaehyuk, Walker, Christopher M., Sandulache, Vlad C., Hennel, Franciszek, Lai, Stephen Y., and Bankson, James A.
- Abstract
Purpose The transient and nonrenewable signal from hyperpolarized metabolites necessitates extensive sequence optimization for encoding spatial, spectral, and dynamic information. In this work, we evaluate the utility of radial single-timepoint and cumulative spectroscopic MRI of hyperpolarized [1-
13 C] pyruvate and its metabolic products at 7 Tesla (T). Methods Simulations of radial echo planar spectroscopic imaging (EPSI) and multiband frequency encoding (MBFE) acquisitions were performed to confirm feasibility and evaluate performance for HP13 C imaging. Corresponding sequences were implemented on a 7T small-animal MRI system, tested in phantom, and demonstrated in a murine model of anaplastic thyroid cancer. Results MBFE provides excellent spectral separation but is susceptible to blurring and T2 * signal loss inherent to using low readout gradients. The higher readout gradients and more flexible spectral encoding for EPSI result in good spatial resolution and spectral separation. Radial acquisition throughout HP signal evolution offers the flexibility for reconstructing spatial maps of mean metabolite distribution and global dynamic time courses of multiple metabolites. Conclusion Radial EPSI and MBFE acquisitions are well-suited for hyperpolarized13 C MRI over short and long durations. Advantages to this approach include robustness to nonstationary magnetization, insensitivity to precise acquisition timing, and versatility for reconstructing dynamically acquired spectroscopic data. Magn Reson Med 72:986-995, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2014
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29. Evaluation of Hyperpolarized [1-13C]-Pyruvate by Magnetic Resonance to Detect Ionizing Radiation Effects in Real Time.
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Sandulache, Vlad C., Chen, Yunyun, Lee, Jaehyuk, Rubinstein, Ashley, Ramirez, Marc S., Skinner, Heath D., Walker, Christopher M., Williams, Michelle D., Tailor, Ramesh, Court, Laurence E., Bankson, James A., and Lai, Stephen Y.
- Subjects
PHYSIOLOGICAL effects of ionizing radiation ,PYRUVATES ,MAGNETIC resonance ,REACTIVE oxygen species ,HEAD & neck cancer treatment ,NECK tumors ,MEDICAL protocols - Abstract
Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-
13 C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping. [ABSTRACT FROM AUTHOR]- Published
- 2014
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30. A Catalyzing Phantom for Reproducible Dynamic Conversion of Hyperpolarized [1-13C]-Pyruvate.
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Walker, Christopher M., Lee, Jaehyuk, Ramirez, Marc S., Schellingerhout, Dawid, Millward, Steven, and Bankson, James A.
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SPECTROSCOPIC imaging ,METABOLITES ,BIOMARKERS ,ENZYME kinetics ,CHEMICAL reactions ,MAGNETIC resonance imaging - Abstract
In vivo real time spectroscopic imaging of hyperpolarized
13 C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-13 C]-pyruvate to [1-13 C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers. [ABSTRACT FROM AUTHOR]- Published
- 2013
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31. A throughput-optimized array system for multiple-mouse MRI.
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Ramirez, Marc S., Lai, Stephen Y., and Bankson, James A.
- Abstract
MRI is a versatile tool for the systematic assessment of anatomical and functional changes in small-animal models of human disease. Its noninvasive nature makes it an ideal candidate for longitudinal evaluations of disease progression, but relatively long scan times limit the number of observations that can be made in a given interval of time, imposing restrictions on experimental design and potentially compromising statistical power. Methods that reduce the overall time required to scan multiple cohorts of animals in distinct experimental groups are therefore highly desirable. Multiple-mouse MRI, in which several animals are simultaneously scanned in a common MRI system, has been successfully used to improve study throughput. However, to best utilize the next generation of small-animal MRI systems that will be equipped with an increased number of receive channels, a paradigm shift from the simultaneous scanning of as many animals as possible to the scanning of a more manageable number, at a faster rate, must be considered. This work explores the tradeoffs between the number of animals to scan at once and the number of array elements dedicated to each animal, to maximize throughput in systems with 16 receive channels. An array system consisting of 15 receive and five transmit coils allows acceleration by a combination of multi-animal and parallel imaging techniques. The array system was designed and fabricated for use on a 7.0-T/30-cm Bruker Biospec MRI system, and tested for high-throughput imaging performance in phantoms and live mice. Results indicate that up to a nine-fold throughput improvement of a single sequence is possible compared with an unaccelerated single-animal acquisition. True data throughput of a contrast-enhanced anatomical study is estimated to be improved by just over six-fold. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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32. Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors.
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Bankson, James A., Walker, Christopher M., Ramirez, Marc S., Stefan, Wolfgang, Fuentes, David, Merritt, Matthew E., Jaehyuk Lee, Sandulache, Vlad C., Yunyun Chen, Liem Phan, Ping-Chieh Chou, Rao, Arvind, Yeung, Sai-Ching J., Mong-Hong Lee, Schellingerhout, Dawid, Conrad, Charles A., Malloy, Craig, Sherry, A. Dean, Lai, Stephen Y., and Hazle, John D.
- Subjects
- *
HYPERPOLARIZATION (Cytology) , *PYRUVATES , *METABOLITES , *PERFUSION , *PHARMACOKINETICS - Abstract
Hyperpolarized 1-13C-pyruvate has shown tremendous promise as an agent for imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging hyperpolarized substrates by magnetic resonance is unlike traditional MRI because signals are highly transient and their spatial distribution varies continuously over their observable lifetime. Therefore, new imaging approaches are needed to ensure optimal measurement under these circumstances. Constrained reconstruction algorithms can integrate prior information, including biophysical models of the substrate/target interaction, to reduce the amount of data that is required for image analysis and reconstruction. In this study, we show that metabolic MRI with hyperpolarized pyruvate is biased by tumor perfusion, and present a new pharmacokinetic model for hyperpolarized substrates that accounts for these effects. The suitability of this model is confirmed by statistical comparison to alternates using data from 55 dynamic spectroscopic measurements in normal animals and murine models of anaplastic thyroid cancer, glioblastoma, and triple-negative breast cancer. The kinetic model was then integrated into a constrained reconstruction algorithm and feasibility was tested using significantly under-sampled imaging data from tumor-bearing animals. Compared to naïve image reconstruction, this approach requires far fewer signal-depleting excitations and focuses analysis and reconstruction on new information that is uniquely available from hyperpolarized pyruvate and its metabolites, thus improving the reproducibility and accuracy of metabolic imaging measurements. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
33. Feasibility of multianimal hyperpolarized (13) C MRS.
- Author
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Ramirez MS, Lee J, Walker CM, Chen Y, Kingsley CV, De La Cerda J, Maldonado KL, Lai SY, and Bankson JA
- Subjects
- Animals, Carbon-13 Magnetic Resonance Spectroscopy economics, Cost-Benefit Analysis, Equipment Design, Feasibility Studies, Heterografts, Lactic Acid metabolism, Mice, Mice, Nude, Neoplasm Transplantation, Phantoms, Imaging, Pyruvic Acid metabolism, Carbon-13 Magnetic Resonance Spectroscopy instrumentation, Carbon-13 Magnetic Resonance Spectroscopy methods, Colonic Neoplasms physiopathology, Energy Metabolism physiology
- Abstract
Purpose: There is great potential for real-time investigation of metabolism with MRS and hyperpolarized (HP) (13) C agents. Unfortunately, HP technology has high associated costs and efficiency limitations that may constrain in vivo studies involving many animals. To improve the throughput of preclinical investigations, we evaluate the feasibility of performing HP MRS on multiple animals simultaneously., Methods: Simulations helped assess the viability of a dual-coil strategy for spatially localized multivolume MRS. A dual-mouse system was assembled and characterized with bench- and scanner-based experiments. Enzyme phantoms mixed with HP [1-(13) C] pyruvate emulated real-time metabolism and offered a controlled mechanism for evaluating system performance. Finally, a normal mouse and a mouse bearing a subcutaneous xenograft of colon cancer were simultaneously scanned in vivo using an agent containing HP [1-(13) C] pyruvate., Results: Geometric separation/rotation, active decoupling, and use of low input impedance preamplifiers permitted an encode-by-channel approach for spatially localized MRS. A precalibrated shim allowed straightforward metabolite differentiation in enzyme phantom and in vivo experiments at 7 Tesla, with performance similar to conventional acquisitions., Conclusion: The initial feasibility of multi-animal HP (13) C MRS was established. Throughput scales with the number of simultaneously scanned animals, demonstrating the potential for significant improvements in study efficiency., (© 2014 Wiley Periodicals, Inc.)
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- 2015
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34. Radial spectroscopic MRI of hyperpolarized [1-(13) C] pyruvate at 7 tesla.
- Author
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Ramirez MS, Lee J, Walker CM, Sandulache VC, Hennel F, Lai SY, and Bankson JA
- Subjects
- Algorithms, Animals, Carbon Isotopes pharmacokinetics, Feasibility Studies, Mice, Mice, Nude, Radiopharmaceuticals pharmacokinetics, Reproducibility of Results, Sensitivity and Specificity, Tissue Distribution, Biomarkers, Tumor metabolism, Electron Spin Resonance Spectroscopy methods, Magnetic Resonance Imaging methods, Pyruvic Acid pharmacokinetics, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology
- Abstract
Purpose: The transient and nonrenewable signal from hyperpolarized metabolites necessitates extensive sequence optimization for encoding spatial, spectral, and dynamic information. In this work, we evaluate the utility of radial single-timepoint and cumulative spectroscopic MRI of hyperpolarized [1-(13) C] pyruvate and its metabolic products at 7 Tesla (T)., Methods: Simulations of radial echo planar spectroscopic imaging (EPSI) and multiband frequency encoding (MBFE) acquisitions were performed to confirm feasibility and evaluate performance for HP (13) C imaging. Corresponding sequences were implemented on a 7T small-animal MRI system, tested in phantom, and demonstrated in a murine model of anaplastic thyroid cancer., Results: MBFE provides excellent spectral separation but is susceptible to blurring and T2 * signal loss inherent to using low readout gradients. The higher readout gradients and more flexible spectral encoding for EPSI result in good spatial resolution and spectral separation. Radial acquisition throughout HP signal evolution offers the flexibility for reconstructing spatial maps of mean metabolite distribution and global dynamic time courses of multiple metabolites., Conclusion: Radial EPSI and MBFE acquisitions are well-suited for hyperpolarized (13) C MRI over short and long durations. Advantages to this approach include robustness to nonstationary magnetization, insensitivity to precise acquisition timing, and versatility for reconstructing dynamically acquired spectroscopic data., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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35. Evaluation of hyperpolarized [1-¹³C]-pyruvate by magnetic resonance to detect ionizing radiation effects in real time.
- Author
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Sandulache VC, Chen Y, Lee J, Rubinstein A, Ramirez MS, Skinner HD, Walker CM, Williams MD, Tailor R, Court LE, Bankson JA, and Lai SY
- Subjects
- Animals, Cell Line, Tumor, Dose-Response Relationship, Radiation, Flow Cytometry, Fluoresceins, Heterografts metabolism, Heterografts radiation effects, Humans, Magnetic Resonance Spectroscopy, Mice, Mice, Nude, Oxidation-Reduction radiation effects, Radiation, Ionizing, Thyroid Carcinoma, Anaplastic, Carbon Isotopes chemistry, Pyruvic Acid chemistry, Reactive Oxygen Species metabolism, Thyroid Neoplasms radiotherapy
- Abstract
Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.
- Published
- 2014
- Full Text
- View/download PDF
36. A catalyzing phantom for reproducible dynamic conversion of hyperpolarized [1-¹³C]-pyruvate.
- Author
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Walker CM, Lee J, Ramirez MS, Schellingerhout D, Millward S, and Bankson JA
- Subjects
- Animals, Carbon Isotopes, Humans, Lactic Acid chemistry, Magnetic Resonance Spectroscopy instrumentation, Phantoms, Imaging, Pyruvic Acid chemistry
- Abstract
In vivo real time spectroscopic imaging of hyperpolarized ¹³C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-¹³C]-pyruvate to [1-¹³C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers.
- Published
- 2013
- Full Text
- View/download PDF
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