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8. High Speed, High Density Intraoperative 3D Optical Topographical Imaging with Efficient Registration to MRI and CT for Craniospinal Surgical Navigation

Author

Jakubovic, Raphael, Guha, Daipayan, Gupta, Shaurya, Lu, Michael, Jivraj, Jamil, Standish, Beau A., Leung, Michael K., Mariampillai, Adrian, Lee, Kenneth, Siegler, Peter, Skowron, Patryk, Farooq, Hamza, Nguyen, Nhu, Alarcon, Joseph, Deorajh, Ryan, Ramjist, Joel, Ford, Michael, Howard, Peter, Phan, Nicolas, Costa, Leo da, Heyn, Chris, Tan, Gamaliel, George, Rajeesh, Cadotte, David W., Mainprize, Todd, Yee, Albert, and Yang, Victor X. D.

Published
2018
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20. Quantification of computational geometric congruence in surface-based registration for spinal intra-operative three-dimensional navigation.

Author

Guha, Daipayan, Jakubovic, Raphael, Leung, Michael K., Ginsberg, Howard J., Fehlings, Michael G., Mainprize, Todd G., Yee, Albert, and Yang, Victor X. D.

Subjects
CERVICAL vertebrae, LUMBAR vertebrae, GEOMETRIC congruences, PHYSICAL sciences, SYMMETRY
Abstract

Background Context: Computer-assisted navigation (CAN) may guide spinal instrumentation, and requires alignment of patient anatomy to imaging. Iterative closest-point (ICP) algorithms register anatomical and imaging surface datasets, which may fail in the presence of geometric symmetry (congruence), leading to failed registration or inaccurate navigation. Here we computationally quantify geometric congruence in posterior spinal exposures, and identify predictors of potential navigation inaccuracy. Methods: Midline posterior exposures were performed from C1-S1 in four human cadavers. An optically-based CAN generated surface maps of the posterior elements at each level. Maps were reconstructed to include bilateral hemilamina, or unilateral hemilamina with/without the base of the spinous process. Maps were fitted to symmetrical geometries (cylindrical/spherical/planar) using computational modelling, and the degree of model fit quantified based on the ratio of model inliers to total points. Geometric congruence was subsequently assessed clinically in 11 patients undergoing midline exposures in the cervical/thoracic/lumbar spine for posterior instrumented fusion. Results: In cadaveric testing, increased cylindrical/spherical/planar symmetry was seen in the high-cervical and subaxial cervical spine relative to the thoracolumbar spine (p<0.001). Extension of unilateral exposures to include the ipsilateral base of the spinous process decreased symmetry independent of spinal level (p<0.001). In clinical testing, increased cylindrical/spherical/planar symmetry was seen in the subaxial cervical relative to the thoracolumbar spine (p<0.001), and in the thoracic relative to the lumbar spine (p<0.001). Symmetry in unilateral exposures was decreased by 20% with inclusion of the ipsilateral base of the spinous process. Conclusions: Geometric congruence is most evident at C1 and the subaxial cervical spine, warranting greater vigilance in navigation accuracy verification. At all levels, inclusion of the base of the spinous process in unilateral registration decreases the likelihood of geometric symmetry and navigation error. This work is important to allow the extension of line-of-sight based registration techniques to minimally-invasive unilateral approaches. [ABSTRACT FROM AUTHOR]

Published
2019
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25. Stereotactic radiosurgery for resected brain metastasis: Cavity dynamics and factors affecting its evolution.

Author

Alghamdi, Majed, Hasan, Yaser, Ruschin, Mark, Atenafu, Eshetu G., Myrehaug, Sten, Chia-Lin Tseng, Spears, Julian, Mainprize, Todd, Sahgal, Arjun, and Soliman, Hany

Subjects
STEREOTACTIC radiosurgery, BRAIN metastasis, POSTOPERATIVE care, MULTIVARIATE analysis, UNIVARIATE analysis
Abstract

Objective: To determine changes in post-surgical cavity volume for metastases based on time from surgery, pre-operative tumor dimensions and other predictors, in patients planned for postoperative stereotactic radiosurgery (SRS). Methods: Patients with resected brain metastases from a primary solid tumor, treated with postoperative surgical cavity SRS from 2008 to 2014 were identified from an institutional prospective database. The segmented three-dimensional (3D) volume of the pre-operative tumor and postoperative surgical cavity were determined based on MRI and percent volume change was calculated. Patients were grouped according to early (<21 days), intermediate (22-42 days), and late (>42 days) intervals based on the number of days between the date of surgery and the treatment planning MRI. Potential predictive factors including tumor size, location, age, dural involvement, and degree of surgical resection were also analyzed. Results: Sixty-one cavities in 59 patients were evaluated. Overall, a significant volume reduction (4cm3, p=0.03) was observed comparing tumor and cavity volumes. For larger tumors, an average volume reduction of 11.6% (p=0.01) was observed compared to an increase of 34.4% in smaller tumors (p=0.69). For both large and small tumors, cavities were larger in the early interval especially for smaller tumors. During the intermediate interval, a significant volume reduction was observed for larger tumors (28%, p=0.0007). Tumor size, dural involvement, age and time from surgery were significant predictors for volume change on univariate analysis. On multivariate analysis, tumor size, dural involvement and time from surgery were significant. Conclusion: Tumor size (>3cm), dural involvement and longer time from surgery were significant predictors of cavity volume reduction. Caution must be taken when treating cavities in the early (<21 days) interval after surgery as it may lead to irradiating more normal tissue especially in small tumors. [ABSTRACT FROM AUTHOR]

Published
2018

26. Optimal Therapies for Newly Diagnosed Elderly Patients with Glioblastoma.

Author

Ironside, Sarah, Das, Sunit, Sahgal, Arjun, Moroney, Claire, Mainprize, Todd, Perry, James, and Perry, James R

Abstract

Opinion Statement: Newly diagnosed elderly patients (age > 65-70 years) with glioblastoma should be treated with a patient-centred approach by a multi-disciplinary team. Chronological age alone should not be considered as a contraindication to treatment with maximal safe surgical resection. A 3-week course of adjuvant radiation and chemotherapy is appropriate in selected elderly patients with favourable Karnofsky performance status (KPS) who cannot tolerate a longer 6-week course of fractionated radiotherapy. The presence or absence of 06-methylguanine-DNA methyltransferase (MGMT) promoter methylation can be used to guide clinical decision-making as both prognostic and predictive biomarkers. This review provides an update and summary of the available evidence for treating newly diagnosed elderly patients with glioblastoma. [ABSTRACT FROM AUTHOR]

Published
2017
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28. NIH workshop report on the trans-agency blood-brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface.

Author

Ochocinska, Margaret J., Zlokovic, Berislav V., Searson, Peter C., Crowder, A. Tamara, Kraig, Richard P., Ljubimova, Julia Y., Mainprize, Todd G., Banks, William A., Warren, Ronald Q., Kindzelski, Andrei, Timmer, William, and Liu, Christina H.

Subjects
BLOOD-brain barrier
Abstract

A trans-agency workshop on the blood-brain interface (BBI), sponsored by the National Heart, Lung and Blood Institute, the National Cancer Institute and the Combat Casualty Care Research Program at the Department of Defense, was conducted in Bethesda MD on June 7-8, 2016. The workshop was structured into four sessions: (1) blood sciences; (2) exosome therapeutics; (3) next generation in vitro blood-brain barrier (BBB) models; and (4) BBB delivery and targeting. The first day of the workshop focused on the physiology of the blood and neuro-vascular unit, blood or biofluid-based molecular markers, extracellular vesicles associated with brain injury, and how these entities can be employed to better evaluate injury states and/or deliver therapeutics. The second day of the workshop focused on technical advances in in vitro models, BBB manipulations and nanoparticle-based drug carrier designs, with the goal of improving drug delivery to the central nervous system. The presentations and discussions underscored the role of the BBI in brain injury, as well as the role of the BBB as both a limiting factor and a potential conduit for drug delivery to the brain. At the conclusion of the meeting, the participants discussed challenges and opportunities confronting BBI translational researchers. In particular, the participants recommended using BBI translational research to stimulate advances in diagnostics, as well as targeted delivery approaches for detection and therapy of both brain injury and disease. [ABSTRACT FROM AUTHOR]

Published
2017
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34. 5th International Symposium on Focused Ultrasound: North Bethesda, MD, USA. 28 August- 1 September 2016

Author

Zaaroor, Menashe, Sinai, Alon, Goldsher, Dorit, Eran, Ayelet, Nassar, Maria, Schlesinger, Ilana, Parker, Jonathon, Ravikumar, Vinod, Ghanouni, Pejman, Stein, Sherman, Halpern, Casey, Krishna, Vibhor, Hargrove, Amelia, Agrawal, Punit, Changizi, Barbara, Bourekas, Eric, Knopp, Michael, Rezai, Ali, Mead, Brian, Kim, Namho, Mastorakos, Panagiotis, Suk, Jung Soo, Miller, Wilson, Klibanov, Alexander, Hanes, Justin, Price, Richard, Wang, Shutao, Olumolade, Oluyemi, Kugelman, Tara, Jackson-Lewis, Vernice, Karakatsani, Maria Eleni (Marilena), Han, Yang, Przedborski, Serge, Konofagou, Elisa, Hynynen, Kullervo, Aubert, Isabelle, Leinenga, Gerhard, Nisbet, Rebecca, Hatch, Robert, Van der Jeugd, Anneke, Evans, Harrison, Götz, Jürgen, Van der Jeugd, Ann, Fishman, Paul, Yarowsky, Paul, Frenkel, Victor, Wei-Bin, Shen, Nguyen, Ben, Sanchez, Carlos Sierra, Acosta, Camilo, Chen, Cherry, Wu, Shih-Ying, Aryal, Muna, Papademetriou, Iason T., Zhang, Yong-Zhi, Power, Chanikarn, McDannold, Nathan, Porter, Tyrone, Kovacs, Zsofia, Kim, Saejeong, Jikaria, Neekita, Qureshi, Farhan, Bresler, Michele, Frank, Joseph, Odéen, Henrik, Chiou, George, Snell, John, Todd, Nick, Madore, Bruno, Parker, Dennis, Pauly, Kim Butts, Marx, Mike, Jonathan, Sumeeth, Grissom, William, Arvanitis, Costas, Clement, Gregory, de Bever, Joshua, Payne, Allison, Christensen, Douglas, Maimbourg, Guillaume, Santin, Mathieu David, Houdouin, Alexandre, Lehericy, Stéphane, Tanter, Mickael, Aubry, Jean Francois, Federau, Christian, Werner, Beat, Paeng, Dong-Guk, Xu, Zhiyuan, Quigg, Anders, Eames, Matt, Jin, Changzhu, Everstine, Ashli, Sheehan, Jason, Lopes, M. Beatriz, Kassell, Neal, Drake, James, Price, Karl, Lustgarten, Lior, Sin, Vivian, Mougenot, Charles, Donner, Elizabeth, Tam, Emily, Hodaie, Mojgan, Waspe, Adam, Looi, Thomas, Pichardo, Samuel, Lee, Wonhye, Chung, Yong An, Jung, Yujin, Song, In-Uk, Yoo, Seung-Schik, Kim, Hyun-Chul, Lee, Jong-Hwan, Caskey, Charles, Zinke, Wolf, Cosman, Josh, Shuman, Jillian, Schall, Jeffrey, Aurup, Christian, Chen, Hong, Kamimura, Hermes, Carneiro, Antonio, Sun, Tao, Nazai, Navid, Patz, Sam, Livingstone, Margaret, Mainprize, Todd, Huang, Yuexi, Alkins, Ryan, Chapman, Martin, Perry, James, Lipsman, Nir, Bethune, Allison, Sahgal, Arjun, Trudeau, Maureen, Liu, Hao-Li, Hsu, Po-Hung, Wei, Kuo-Chen, Sutton, Jonathan, Alexander, Phillip, Miller, Eric, Kobus, Thiele, Carpentier, Alexandre, Canney, Michael, Vignot, Alexandre, Beccaria, Kevin, Leclercq, Delphine, Lafon, Cyril, Chapelon, Jean Yves, Hoang-Xuan, Khe, Delattre, Jean-Yves, Idbaih, Ahmed, Moore, David, Xu, Alexis, Schmitt, Paul, Foley, Jessica, Sukovich, Jonathan, Cain, Charles, Pandey, Aditya, Chaudhary, Neeraj, Camelo-Piragua, Sandra, Allen, Steven, Cannata, Jon, Teofilovic, Dejan, Bertolina, Jim, Hall, Timothy, Xu, Zhen, Grondin, Julien, Ferrera, Vincent, ter Haar, Gail, Mouratidis, Petros, Repasky, Elizabeth, Timbie, Kelsie, Badr, Lena, Campbell, Benjamin, McMichael, John, Buckner, Andrew, Prince, Jessica, Stevens, Aaron, Bullock, Timothy, Skalina, Karin, Guha, Chandan, Orsi, Franco, Bonomo, Guido, Vigna, Paolo Della, Mauri, Giovanni, Varano, Gianluca, Schade, George, Wang, Yak-Nam, Pillarisetty, Venu, Hwang, Joo Ha, Khokhlova, Vera, Bailey, Michael, Khokhlova, Tatiana, Sinilshchikov, Ilya, Yuldashev, Petr, Andriyakhina, Yulia, Kreider, Wayne, Maxwell, Adam, Sapozhnikov, Oleg, Partanen, Ari, Lundt, Jonathan, Preusser, Tobias, Haase, Sabrina, Bezzi, Mario, Jenne, Jürgen, Langø, Thomas, Midiri, Massimo, Mueller, Michael, Sat, Giora, Tanner, Christine, Zangos, Stephan, Guenther, Matthias, Melzer, Andreas, Menciassi, Arianna, Tognarelli, Selene, Cafarelli, Andrea, Diodato, Alessandro, Ciuti, Gastone, Rothluebbers, Sven, Schwaab, Julia, Strehlow, Jan, Mihcin, Senay, Tretbar, Steffen, Payen, Thomas, Palermo, Carmine, Sastra, Steve, Olive, Kenneth, Adams, Matthew, Salgaonkar, Vasant, Scott, Serena, Sommer, Graham, Diederich, Chris, Vidal-Jove, Joan, Perich, Eloi, Ruiz, Antonio, Velat, Manuela, Melodelima, David, Dupre, Aurelien, Vincenot, Jeremy, Yao, Chen, Perol, David, Rivoire, Michel, Tucci, Samantha, Mahakian, Lisa, Fite, Brett, Ingham, Elizabeth, Tam, Sarah, Hwang, Chang-il, Tuveson, David, Ferrara, Katherine, Scionti, Stephen, Chen, Lili, Cvetkovic, Dusica, Chen, Xiaoming, Gupta, Roohi, Wang, Bin, Ma, Charlie, Bader, Kenneth, Haworth, Kevin, Holland, Christy, Sanghvi, Narendra, Carlson, Roy, Chen, Wohsing, Chaussy, Christian, Thueroff, Stefan, Cesana, Claudio, Bellorofonte, Carlo, Wang, Qingguo, Wang, Han, Wang, Shengping, Zhang, Junhai, Bazzocchi, Alberto, Napoli, Alessandro, Staruch, Robert, Bing, Chenchen, Shaikh, Sumbul, Nofiele, Joris, Szczepanski, Debra, Staruch, Michelle Wodzak, Williams, Noelle, Laetsch, Theodore, Chopra, Rajiv, Rosenberg, Jarrett, Bitton, Rachelle, LeBlang, Suzanne, Meyer, Joshua, Hurwitz, Mark, Yarmolenko, Pavel, Celik, Haydar, Eranki, Avinash, Beskin, Viktoriya, Santos, Domiciano, Patel, Janish, Oetgen, Matthew, Kim, AeRang, Kim, Peter, Sharma, Karun, Chisholm, Alexander, Aleman, Dionne, Scipione, Roberto, Temple, Michael, Amaral, Joao Guilherme, Endre, Ruby, Lamberti-Pasculli, Maria, de Ruiter, Joost, Campbell, Fiona, Stimec, Jennifer, Gupta, Samit, Singh, Manoj, Hopyan, Sevan, Czarnota, Gregory, Brenin, David, Rochman, Carrie, Kovatcheva, Roussanka, Vlahov, Jordan, Zaletel, Katja, Stoinov, Julian, Bucknor, Matthew, Rieke, Viola, Shim, Jenny, Koral, Korgun, Lang, Brian, Wong, Carlos, Lam, Heather, Shinkov, Alexander, Hu, Jim, Zhang, Xi, Macoskey, Jonathan, Ives, Kimberly, Owens, Gabe, Gurm, Hitinder, Shi, Jiaqi, Pizzuto, Matthew, Dillon, Christopher, Christofferson, Ivy, Hilas, Elaine, Shea, Jill, Greillier, Paul, Ankou, Bénédicte, Bessière, Francis, Zorgani, Ali, Pioche, Mathieu, Kwiecinski, Wojciech, Magat, Julie, Melot-Dusseau, Sandrine, Lacoste, Romain, Quesson, Bruno, Pernot, Mathieu, Catheline, Stefan, Chevalier, Philippe, Marquet, Fabrice, Bour, Pierre, Vaillant, Fanny, Amraoui, Sana, Dubois, Rémi, Ritter, Philippe, Haïssaguerre, Michel, Hocini, Mélèze, Bernus, Olivier, Tebebi, Pamela, Burks, Scott, Milo, Blerta, Gertner, Michael, Zhang, Jimin, Wong, Andrew, Liu, Yu, Kheirolomoom, Azadeh, Seo, Jai, Watson, Katherine, Zhang, Hua, Foiret, Josquin, Borowsky, Alexander, Xu, Doudou, Thanou, Maya, Centelles, Miguell, Wright, Mike, Amrahli, Maral, So, Po-Wah, Gedroyc, Wladyslaw, Kneepkens, Esther, Heijman, Edwin, Keupp, Jochen, Weiss, Steffen, Nicolay, Klaas, Grüll, Holger, Nagle, Matthew, Nikolaeva, Anastasia V., Terzi, Marina E., Tsysar, Sergey A., Cunitz, Bryan, Mourad, Pierre, Downs, Matthew, Yang, Georgiana, Wang, Qi, Chen, Johnny, Farry, Justin, Dixon, Adam, Du, Zhongmin, Dhanaliwala, Ali, Hossack, John, Ranjan, Ashish, Maples, Danny, Wardlow, Rachel, Malayer, Jerry, Ramachandran, Akhilesh, Namba, Hirofumi, Kawasaki, Motohiro, Izumi, Masashi, Kiyasu, Katsuhito, Takemasa, Ryuichi, Ikeuchi, Masahiko, Ushida, Takahiro, Crake, Calum, Kothapalli, Satya V. V. N., Leighton, Wan, Wang, Zhaorui, Gach, H. Michael, Straube, William, Altman, Michael, Kim, Young-sun, Lim, Hyo Keun, Rhim, Hyunchul, van Breugel, Johanna, Braat, Manon, Moonen, Chrit, van den Bosch, Maurice, Ries, Mario, Marrocchio, Cristina, Dababou, Susan, Lee, Jae Young, Chung, Hyun Hoon, Kang, Soo Yeon, Kang, Kook Jin, Son, Keon Ho, Zhang, Dandan, Plata, Juan, Jones, Peter, Pascal-Tenorio, Aurea, Bouley, Donna, Bond, Aaron, Dallapiazza, Robert, Huss, Diane, Warren, Amy, Sperling, Scott, Gwinn, Ryder, Shah, Binit, Elias, W. Jeff, Curley, Colleen, Zhang, Ying, Negron, Karina, Abounader, Roger, Samiotaki, Gesthimani, Tu, Tsang-Wei, Papadakis, Georgios, Hammoud, Dima, Silvestrini, Matthew, Wolfram, Frank, Güllmar, Daniel, Reichenbach, Juergen, Hofmann, Denis, Böttcher, Joachim, Schubert, Harald, Lesser, Thomas G., Almquist, Scott, Camarena, Francisco, Jiménez-Gambín, Sergio, Jiménez, Noé, Chang, Jin Woo, Chaplin, Vandiver, Griesenauer, Rebekah, Miga, Michael, Ellens, Nicholas, Airan, Raag, Quinones-Hinojosa, Alfredo, Farahani, Keyvan, Feng, Xue, Fielden, Samuel, Zhao, Li, Wintermark, Max, Meyer, Craig, Guo, Sijia, Lu, Xin, Zhuo, Jiachen, Xu, Su, Gullapalli, Rao, Gandhi, Dheeraj, Brokman, Omer, Baek, Hongchae, Kim, Hyungmin, Leung, Steven, Webb, Taylor, Vykhodtseva, Natalia, Nguyen, Thai-Son, Park, Chang Kyu, Park, Sang Man, Jung, Na Young, Kim, Min Soo, Chang, Won Seok, Jung, Hyun Ho, Plaksin, Michael, Weissler, Yoni, Shoham, Shy, Kimmel, Eitan, Rosnitskiy, Pavel B., Krupa, Steve, Hazan, Eilon, Naor, Omer, Levy, Yoav, Maimon, Noam, Brosh, Inbar, Kahn, Itamar, Cahill, Jessica, Colas, Elodie Constanciel, Wydra, Adrian, Maev, Roman, Aly, Amirah, Sesenoglu-Laird, Ozge, Padegimas, Linas, Cooper, Mark, Waszczak, Barbara, Tehrani, Seruz, Slingluff, Craig, Larner, James, Andarawewa, Kumari, Ozhinsky, Eugene, Shah, Rutwik, Krug, Roland, Deckers, Roel, Linn, Sabine, Suelmann, Britt, Witkamp, Arjen, Vaessen, Paul, van Diest, Paul, Bartels, Lambertus W., Bos, Clemens, Borys, Nicolas, Storm, Gert, Van der Wall, Elsken, Farr, Navid, Alnazeer, Moez, Katti, Prateek, Wood, Bradford, Farrer, Alexis, Ferrer, Cyril, de Senneville, Baudouin Denis, van Stralen, Marijn, Liu, Jingfei, Leach, J. Kent, Zidowitz, Stephan, Lee, Hsin-Lun, Hsu, Fang-Chi, Kuo, Chia-Chun, Jeng, Shiu-Chen, Chen, Tung-Ho, Yang, Nai-Yi, Chiou, Jeng-Fong, Kao, Yi-tzu, Pan, Chia-Hsin, Wu, Jing-Fu, Tsai, Yi-Chieh, Johnson, Sara, Li, Dawei, He, Ye, Karakitsios, Ioannis, Schwenke, Michael, Demedts, Daniel, Xiao, Xu, Cavin, Ian, Minalga, Emilee, Merrill, Robb, Hadley, Rock, Ramaekers, Pascal, de Greef, Martijn, Shahriari, Kian, Parvizi, Mohammad Hossein, Asadnia, Kiana, Chamanara, Marzieh, Kamrava, Seyed Kamran, Chabok, Hamid Reza, Stein, Ruben, Muller, Sébastien, Tan, Jeremy, Zachiu, Cornel, Erasmus, Hans-Peter, Van Arsdell, Glen, Benson, Lee, Jang, Kee W., Angstadt, Mary, Lewis, Bobbi, McLean, Hailey, Hoogenboom, Martijn, Eikelenboom, Dylan, den Brok, Martijn, Wesseling, Pieter, Heerschap, Arend, Fütterer, Jurgen, Adema, Gosse, Wang, Kevin, Zhong, Pei, Joy, Joyce, McLeod, Helen, Kim, Harry, Lewis, Matthew, Ozilgen, Arda, Zahos, Peter, Coughlin, Dezba, Tang, Xinyan, Lotz, Jeff, Jedruszczuk, Kathleen, Gulati, Amitabh, Solomon, Stephen, Kaye, Elena, Mugler, John, Barbato, Gaetano, Scoarughi, Gian Luca, Corso, Cristiano, Gorgone, Alessandro, Migliore, Ilaria Giuseppina, Larrabee, Zachary, Hananel, Arik, Aubry, Jean-Francois, Negussie, Ayele, Wilson, Emmanuel, Seifabadi, Reza, Moon, Hyungwon, Kang, Jeeun, Sim, Changbeom, Chang, Jin Ho, Kim, Hyuncheol, Lee, Hak Jong, Sasaki, Noboru, Takiguchi, Mitsuyoshi, Sebeke, Lukas, Luo, Xi, de Jager, Bram, Heemels, Maurice, Abraham, Christopher, Curiel, Laura, Berriet, Rémi, Janát-Amsbury, Margit, Corea, Joseph, Ye, Patrick Peiyong, Arias, Ana Clauda, Lustig, Micheal, and Svedin, Bryant

Published
2016
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36. Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization.

Author

Naoki Yokota, Nicola Jane, Mainprize, Todd G., Taylor, Michael D., Kohata, Tomohiko, Loreto, Michael, Shigeo Ueda, Michael, Dura, Wieslaw, Grajkowska, Wiesia, Kuo, John S., and Rutka, James T.

Subjects
*MEDULLOBLASTOMA, *GENETIC regulation, *GENE expression, *NUCLEIC acid hybridization, *CEREBELLUM, *CYTOPLASMIC granules
Abstract

To increase our understanding of the molecular pathogenesis of medulloblastoma (MB), we utilized the technique of suppression subtractive hybridization (SSH) to identify genes that are dysregulated in MB when compared to cerebellum. SSH-enriched cDNA libraries from both human and Ptch+/- heterozygous murine MBs were generated by subtracting common cDNAs from corresponding non-neoplastic cerebellum. For the human classic MB library, total human cerebellar RNA was used as control tissue; for the Ptch+/- heterozygous MB, non-neoplastic cerebellum from an unaffected Ptch+/- littermate was used as the control. Through differential screening of these libraries, over 100 upregulated tumor cDNA fragments were isolated, sequenced and identified with the NCBI BLAST program. From these, we selected genes involved in cellular proliferation, antiapoptosis, and cerebellar differentiation for further analysis. Upregulated genes identified in the human MB library included Unc33-like protein (ULIP), SOX4, Neuronatin (NNAT), the mammalian homologue of Drosophila BarH-like 1(BARHL1), the nuclear matix protein NRP/B (ENC1), and the homeobox OTX2 gene. Genes found to be upregulated in the murine MB library included cyclin D2 (Ccnd2), thymopoietin (Tmpo), Musashi-1 (Msh1), protein phosphatase 2A inhibitor-2 (I-2pp2a), and Unc5h4(D). Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the mRNA expression levels for these genes were markedly higher in human MBs than in cerebellum. Western blot analysis was used to further confirm the overexpression of a subset of these genes at the protein level. Notch pathway overactivity was demonstrated in the TE671 MB cell line expressing high levels of MSH1 through HES1-Luciferase transfections. This study has revealed a panel of developmentally regulated genes that may be involved in the pathogenesis of MB.Oncogene (2004) 23, 3444-3453. doi:10.1038/sj.onc.1207475 Published online 5 April 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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37. Mutations in SUFU predispose to medulloblastoma.

Author

Taylor, Michael D., Liu, Ling, Raffel, Corey, Hui, Chi-chung, Mainprize, Todd G., Zhang, Xiaoyun, Agatep, Ron, Chiappa, Sharon, Gao, Luzhang, Lowrance, Anja, Hao, Aihau, Goldstein, Alisa M., Stavrou, Theodora, Scherer, Stephen W., Dura, Wieslaw T., Wainwright, Brandon, Squire, Jeremy A., Rutka, James T., and Hogg, David

Subjects
MEDULLOBLASTOMA, HEDGEHOG signaling proteins, MICROBIAL mutation, RECOMBINANT proteins
Abstract

The sonic hedgehog (SHH) signaling pathway directs the embryonic development of diverse organisms and is disrupted in a variety of malignancies. Pathway activation is triggered by binding of hedgehog proteins to the multipass Patched-1 (PTCH) receptor, which in the absence of hedgehog suppresses the activity of the seven-pass membrane protein Smoothened (SMOH). De-repression of SMOH culminates in the activation of one or more of the GLI transcription factors that regulate the transcription of downstream targets. Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal-cell carcinomas, medulIoblastomas and other cancers (a pattern consistent with nevoid basal-cell carcinoma syndrome, NBCCS). In keeping with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene occur in sporadic basal-cell carcinomas and medulloblastomas. We report here that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele. Several of these mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism. [ABSTRACT FROM AUTHOR]

Published
2002
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38. Medulloblastoma in a Child with Rubenstein-Taybi Syndrome: Case Report and Review of the Literature.

Author

Taylor, Michael D., Mainprize, Todd G., Rutka, James T., Becker, Lawrence, Bayani, Jane, and Drake, James M.

Subjects
*MEDULLOBLASTOMA, *PEDIATRICS, *CHILDREN, *CHROMOSOMES, *BASAL cell nevus syndrome, *GENES
Abstract

Although medulloblastoma is usually sporadic, there are a number of uncommon predisposing germline mutation syndromes, including: Gorlin’s Syndrome, Turcot’s Syndrome and Li-Fraumeni Syndrome. Patients with Rubenstein-Taybi Syndrome secondary to mutation/deletion of the CBP gene on chromosome 16 are predisposed to a variety of developmental anomalies as well as cancer. We report a child with Rubenstein-Taybi syndrome who developed a cerebellar medulloblastoma and review the literature on Rubenstein-Taybi Syndrome and pediatric medulloblastoma. As the product of the CBP gene functions in a variety of signaling pathways, we discuss the molecular implications of findings a medulloblastoma in a child with Rubenstein-Taybi Syndrome.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2001
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39. First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound.

Author

Abrahao, Agessandro, Meng, Ying, Llinas, Maheleth, Huang, Yuexi, Hamani, Clement, Mainprize, Todd, Aubert, Isabelle, Heyn, Chinthaka, Black, Sandra E., Hynynen, Kullervo, Lipsman, Nir, and Zinman, Lorne

Subjects
AMYOTROPHIC lateral sclerosis, BLOOD-brain barrier, CENTRAL nervous system, MOTOR cortex, TARGETED drug delivery, MICROBUBBLE diagnosis, HIGH-intensity focused ultrasound
Abstract

MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS. MR-focused ultrasound can be used to transiently open the blood-brain barrier (BBB). Here, the authors report the results of a first-in-human trial on four patients with amyotrophic lateral sclerosis (ALS), showing that the procedure reversibly permeabilised the BBB in the motor cortex without complications, and suggest that the procedure could in the future be used to increase drug delivery in ALS patients. [ABSTRACT FROM AUTHOR]

Published
2019
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40. Optical Topographic Imaging for Spinal Intraoperative Three-Dimensional Navigation in Mini-Open Approaches: A Prospective Cohort Study of Initial Preclinical and Clinical Feasibility.

Author

Guha, Daipayan, Jakubovic, Raphael, Alotaibi, Naif M., Klostranec, Jesse M., Saini, Sidharth, Deorajh, Ryan, Gupta, Shaurya, Fehlings, Michael G., Mainprize, Todd G., Yee, Albert, and Yang, Victor X.D.

Subjects
*OPTICAL images, *MINIMALLY invasive procedures, *LONGITUDINAL method, *COHORT analysis, *ANATOMICAL planes
Abstract

Computer-assisted three-dimensional navigation often guides spinal instrumentation. Optical topographic imaging (OTI) offers comparable accuracy and significantly faster registration relative to current navigation systems in open posterior thoracolumbar exposures. We validate the usefulness and accuracy of OTI in minimally invasive spinal approaches. Mini-open midline posterior exposures were performed in 4 human cadavers. Square exposures of 25, 30, 35, and 40 mm were registered to preoperative computed tomography imaging. Screw tracts were fashioned using a tracked awl and probe with instrumentation placed. Navigation data were compared with screw positions on postoperative computed tomography imaging, and absolute translational and angular deviations were computed. In vivo validation was performed in 8 patients, with mini-open thoracolumbar exposures and percutaneous placement of navigated instrumentation. Navigated instrumentation was performed in the previously described manner. For 37 cadaveric screws, absolute translational errors were (1.79 ± 1.43 mm) and (1.81 ± 1.51 mm) in the axial and sagittal planes, respectively. Absolute angular deviations were (3.81 ± 2.91°) and (3.45 ± 2.82°), respectively (mean ± standard deviation). The number of surface points registered by the navigation system, but not exposure size, correlated positively with the likelihood of successful registration (odds ratio, 1.02; 95% confidence interval, 1.009–1.024; P < 0.001). Fifty-five in vivo thoracolumbar pedicle screws were analyzed. Overall (mean ± standard deviation) axial and sagittal translational errors were (1.79 ± 1.41 mm) and (2.68 ± 2.26 mm), respectively. Axial and sagittal angular errors were (3.63° ± 2.92°) and (4.65° ± 3.36°), respectively. There were no radiographic breaches >2 mm or any neurovascular complications. OTI is a novel navigation technique previously validated for open posterior exposures and in this study has comparable accuracy for mini-open minimally invasive surgery exposures. The likelihood of successful registration is affected more by the geometry of the exposure than by its size. [ABSTRACT FROM AUTHOR]

Published
2019
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41. 235 Radiation Necrosis Following Five Daily Fractions of Stereotactic Radiotherapy for Surgical Cavities and Intact Brain Metastases.

Author

Faruqi, Salman, Soliman, Hany, Myrehaug, Sten, Zeng, K. Liang, Husain, Zain, Atenafu, Eshetu, Tseng, Chia-Lin, Das, Sunit, Perry, James, Maralani, Pejman, Heyn, Chris, Mainprize, Todd, Ruschin, Mark, and Sahgal, Arjun

Subjects
*STEREOTACTIC radiotherapy, *BRAIN metastasis, *STEREOTACTIC radiosurgery, *NECROSIS, *RADIATION, *FRACTIONS
Published
2019
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