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1. Breath-Hold Induced Cerebrovascular Reactivity Measurements Using Optimized Pseudocontinuous Arterial Spin Labeling

Author

Sergio M. Solis-Barquero, Rebeca Echeverria-Chasco, Marta Calvo-Imirizaldu, Elena Cacho-Asenjo, Antonio Martinez-Simon, Marta Vidorreta, Pablo D. Dominguez, Reyes García de Eulate, Miguel Fernandez-Martinez, and María A. Fernández-Seara

Subjects
arterial spin labeling, breath-hold, cerebrovascular reactivity, cerebral blood flow, hypercapnia, Physiology, QP1-981
Abstract

A pseudocontinuous arterial spin labeling (PCASL) sequence combined with background suppression and single-shot accelerated 3D RARE stack-of-spirals was used to evaluate cerebrovascular reactivity (CVR) induced by breath-holding (BH) in ten healthy volunteers. Four different models designed using the measured change in PETCO2 induced by BH were compared, for CVR quantification. The objective of this comparison was to understand which regressor offered a better physiological model to characterize the cerebral blood flow response under BH. The BH task started with free breathing of 42 s, followed by interleaved end-expiration BHs of 21 s, for ten cycles. The total scan time was 12 min and 20 s. The accelerated readout allowed the acquisition of PCASL data with better temporal resolution than previously used, without compromising the post-labeling delay. Elevated CBF was observed in most cerebral regions under hypercapnia, which was delayed with respect to the BH challenge. Significant statistical differences in CVR were obtained between the different models in GM (p < 0.0001), with ramp models yielding higher values than boxcar models and between the two tissues, GM and WM, with higher values in GM, in all the models (p < 0.0001). The adjustment of the ramp amplitude during each BH cycle did not improve the results compared with a ramp model with a constant amplitude equal to the mean PETCO2 change during the experiment.

Published
2021
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2. Contributors

Author

Hani Abujudeh, Andreas Adam, Hassan M. Ahmad, Sun Ho Ahn, Kamran Ahrar, Morvarid Alaghmand, Agaicha Alfidja, Ahmad I. Alomari, Gennaro Ambrosanio, Soon Ghee Ang, John Frederick Angle, Gary M. Ansel, Bassel Atassi, Julien Auriol, Juan Carlos Baez, Curtis W. Bakal, Jörn Oliver Balzer, Joel E. Barbato, Brad P. Barnett, Gamal Baroud, Carlo Bartolozzi, Jason R. Bauer, Richard Arthur Baum, Kevin Walter Bell, Jacqueline A. Bello, Jennifer L. Berkeley, Michael A. Bettmann, Mario Bezzi, José I. Bilbao, Deniz Bilecen, Christoph A. Binkert, Haraldur Bjarnason, James H. Black, Francine Blei, Brian M. Block, Marc Bohner, Amman Bolia, Irene Boos, Charles F. Botti, Louis Boyer, Elena Bozzi, Peter Reynolds Bream, Rachel F. Brem, Mark F. Brodie, Allan L. Brook, Benjamin S. Brooke, Duncan Mark Brooks, Daniel B. Brown, Karen T. Brown, James P. Burnes, Patricia E. Burrows, Justin John Campbell, Colin P. Cantwell, Thierry Carreres, John A. Carrino, Lucie Cassagnes, Pascal Chabrot, Abbas Afif Chamsuddin, Richard Chang, Lakhmir S. Chawla, Hank (Han) K. Chen, Yung-Hsin Chen, Rush Hamilton Chewning, Kenneth H. Cho, Albert K. Chun, Timothy W.I. Clark, Felipe B. Collares, Luca Cova, Laura Crocetti, Charles D. Crum, T. Andrew Currier, Ferenc Czeyda-Pommersheim, Michael D. Dake, Michael David Darcy, L. Mark Dean, Thierry De Baère, Sudhen B. Desai, Alvaro A. Diano, Robert G. Dixon, Pablo D. Dominguez, Robert F. Dondelinger, Gregory J. Dubel, Clifford J. Eskey, Jan A. Eubig, Salomão Faintuch, Ronald N. Fairman, Chieh-Min Fan, Fabrizio Fanelli, Mark A. Farber, Laura M. Fayad, Peter F. Ford, Brian Funaki, Andreas Gabelmann, Dmitri A. Gagarin, Philippe Gailloud, Suvranu Ganguli, Lorenzo García-García, Vanessa L. Gates, Tony Geoghegan, Debra A. Gervais, Jean-Francois H. Geschwind, Matthew B. Gillbert, Mark F. Given, Y. Pierre Gobin, S. Nahum Goldberg, Theodore S. Grawbow, Roy K. Greenberg, Brian Grieme, Klaus D. Hagspiel, Keith W. Hamilton, Klaus A. Hausegger, Markus H. Heim, Robert C. Heng, Joshua A. Hirsch, J. Todd Hobelmann, Andrew H. Holden, Ed Horn, Oluwatoyin R. Idowu, Tiziana Ierace, Elizabeth Ann Ignacio, Zubin Irani, Roberto Izzo, James E. Jackson, Augustinus L. Jacob, Priya Jaga, Francis Joffre, Matthew S. Johnson, Chauncey T. Jones, Sanjeeva P. Kalva, Anthony W. Kam, Sridhar Kamath, Krishna Kandarpa, Jeffrey M. Katz, John A. Kaufman, Alexis D. Kelekis, Frederick S. Keller, Robert K. Kerlan, David Kessel, Verena Khan, Kanika Khanna, Neil M. Khilnani, Hyun S. Kim, Hiro Kiyosue, Sebastian Kos, Gaurav Kumar, Maxim Kupershmidt, Vineel Kurli, Jeanne M. LaBerge, Pierre-Yves Laffy, Carlos Lanciego, Elvira V. Lang, Arcangelo L. Lavanga, Leo Patrick Lawler, Judy M. Lee, Michael J. Lee, Thomas Lemettre, Riccardo Lencioni, Yean L. Lim, Robert J. Lewandowski, John J. Lewin, Curtis Allen Lewis, Changqing Li, Eleni Liapi, Rafael H. Llinas, Reinhard Loose, Stuart M. Lyon, Patrick C. Malloy, Michael J. Manzano, Marie Agnes Marachet, Jean-Baptiste Martin, Antonio Martínez-Cuesta, M. Victoria Marx, John M. Mathis, Alan H. Matsumoto, Matthew A. Mauro, Gordon McLennan, Simon J. McPherson, Hugh McSwain, Steven Greene Meranze, Todd S. Miller, Robert J. Min, Sally E. Mitchell, Stephan Moll, Jeffrey I. Mondschein, Laurel E. Moore, Jose Pablo Morales, Robert A. Morgan, Hiromu Mori, Paul R. Morrison, Stefan Müller-Hülsbeck, Kieran P.J. Murphy, Timothy P. Murphy, Mario Muto, Aravinda Nanjundappa, Juan C. Narvaez, Rodrigo Gomes Do Nascimento, Albert A. Nemcek, Ali Noor, Luigi Novelli, Gianluigi Orgera, Philippe Otal, Randall P. Owen, Aalpen A. Patel, Sandra Pauls, Monica Smith Pearl, Giuseppe Pelle, Olivier Pellerin, Daniel Picus, Jeffrey S. Pollak, Rupert Horst Portugaller, Batya R. Radzik, Suman W. Rathbun, Anne Ravel, Charles E. Ray, Mahmood K. Razavi, Howard A. Riina, Anne Roberts, Alain Roche, Eric E. Roselli, Robert J. Rosen, Plinio Rossi, Hervé Rousseau, Stefan G. Ruehm, Diego San Millán Ruíz, John H. Rundback, Wael E.A. Saad, Tarun Sabharwal, Gloria Maria Martinez Salazar, John Vito Salerno, Riad Salem, Marc R. Sapoval, Shawn N. Sarin, Sanjiv Sharma, Ashot Shekoyan, Ji Hoon Shin, Naomi N. Silva, Stuart G. Silverman, Charan Kamal Singh, Constantinos T. Sofocleous, Luigi Solbiati, Stephen B. Solomon, Ho-Young Song, Kean H. Soon, Thomas A. Sos, Michael C. Soulen, James B. Spies, M.J. Bernadette Stallmeyer, Joseph M. Stavas, LeAnn Simmons Stokes, Ernst-Peter Strecker, Michael B. Streiff, Deepak Sudheendra, Walter A. Tan, Elizabeth R. Tang, Mahsa R. Tehrani, Mathew M. Thompson, Kenneth R. Thompson, Gina D. Tran, Scott O. Trerotola, David Trost, Nirman Tulsyan, Kemal Tuncali, Ulku Cenk Turba, Renan Uflacker, Eric van Sonnenberg, Prasanna Vasudevan, Anthony C. Venbrux, Tom Vesely, Bogdan Vierasu, Rachel L. Vile, Isabel Vivas, Dierk Vorwerk, David L. Waldman, Michael J. Wallace, Anthony F. Watkinson, Peter N. Waybill, Joshua L. Weintraub, Robert I. White, Mark H. Wholey, Bradford D. Winters, Robert Wityk, Edward Y. Woo, Bradford J. Wood, Gerald M. Wyse, Albert J. Yoo, Chang Jin Yoon, Rex C. Yung, Soraya Zaid, Steven M. Zangan, Grace M. Zawistowski, Fabio Zeccolini, Eberhard Zeitler, Dianbo Zhang, Gregg H. Zoarski, and Christoph L. Zollikofer

Published
2010

3. DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report

Author

Sonia Tejada, Ricardo Díez-Valle, Pablo D. Domínguez, Ana Patiño-García, Marisol González-Huarriz, Juan Fueyo, Cande Gomez-Manzano, Miguel Angel Idoate, Joanna Peterkin, and Marta M. Alonso

Subjects
diffuse intrinsic pontine gliomas, phase I clinical trial, oncolytic virus, delta-24-RGD, DNX-2401, intratumoral, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive glial brain tumors that primarily affect children, for which there is no curative treatment. Median overall survival is only one year. Currently, the scientific focus is on expanding the knowledge base of the molecular biology of DIPG, and identifying effective therapies. Oncolytic adenovirus DNX-2401 is a replication-competent, genetically modified virus capable of infecting and killing glioma cells, and stimulating an anti-tumor immune response. Clinical trials evaluating intratumoral DNX-2401 in adults with recurrent glioblastoma have demonstrated that the virus has a favorable safety profile and can prolong survival. Subsequently, these results have encouraged the transition of this biologically active therapy from adults into the pediatric population. To this aim, we have designed a clinical Phase I trial for newly diagnosed pediatric DIPG to investigate the feasibility, safety, and preliminary efficacy of delivering DNX-2401 into tumors within the pons following biopsy. This case report presents a pediatric patient enrolled in this ongoing Phase I trial for children and adolescents with newly diagnosed DIPG. The case involves an 8-year-old female patient with radiologically diagnosed DIPG who underwent stereotactic tumor biopsy immediately followed by intratumoral DNX-2401 in the same biopsy track. Because there were no safety concerns or new neurological deficits, the patient was discharged 3 days after the procedures. To our knowledge, this is the first report of intratumoral DNX-2401 for a patient with DIPG in a clinical trial. We plan to demonstrate that intratumoral delivery of an oncolytic virus following tumor biopsy for pediatric patients with DIPG is a novel and feasible approach and that DNX-2401 represents an innovative treatment for the disease.

Published
2018
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