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Start Over Author "Kovacs, Zsofia I." Publication Type Academic Journals
10 results on '"Kovacs, Zsofia I."'

5. Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat.

Author

Tu, Tsang-Wei, Kovacs, Zsofia I., Sundby, Maggie, Witko, Jaclyn A., Papadakis, Georgios Z., Reid, William C., Hammoud, Dima A., and Frank, Joseph A.

Subjects
DIFFUSION tensor imaging, MAGNETIZATION transfer, MICROBUBBLES, CENTRAL nervous system, BRAIN
Abstract

Blood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2∗w, gadolinium (Gd) enhanced T1w] is used to monitor the effects of pFUS+MB on BBBO and/or assess whether sonication results in parenchymal damage. This study employed multimodal MRI techniques and 18F-Fludeoxyglucose (FDG) PET to evaluate the effects of single and multiple weekly pFUS+MB sessions on morphology and glucose utilization levels in the rat cortex and hippocampus. pFUS was performed with 0.548 MHz transducer with a slow infusion over 1 min of OptisonTM (5–8 × 107 MB) in nine focal points in cortex and four in hippocampus. During pFUS+MB treatment, Gd-T1w was performed at 3 T to confirm BBBO, along with subsequent T2w, T2∗w, DTI and glucose CEST (glucoCEST)-weighted imaging by high field 9.4 T and compared with FDG-PET and immunohistochemistry. Animals receiving a single pFUS+MB exhibited minimal hypointense voxels on T2∗w. Brains receiving multiple pFUS+MB treatments demonstrated persistent T2w and T2∗ abnormalities associated with changes in DTI and glucoCEST when compared to contralateral parenchyma. Decreased glucoCEST contrast was substantiated by FDG-PET in cortex following multiple sonications. Immunohistochemistry showed significantly dilated vessels and decreased neuronal glucose transporter (GLUT3) expression in sonicated cortex and hippocampus without changes in neuronal counts. These results suggest the importance to standardize MRI protocols in concert with advanced imaging techniques when evaluating long term effects of pFUS+MB BBBO in clinical trials for neurological diseases. [ABSTRACT FROM AUTHOR]

Published
2020
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6. Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells.

Author

Jr.Bryant, L. Henry, Kim, Saejeong J., Hobson, Matthew, Milo, Blerta, Kovacs, Zsofia I., Jikaria, Neekita, Lewis, Bobbi K., Aronova, Maria A., Sousa, Alioscka A., Zhang, Guofeng, Leapman, Richard D., and Frank, Joseph A.

Subjects
HEPARIN, STEM cells, POLYSACCHARIDES, CELLS, NANOTECHNOLOGY
Abstract

Stem cell-based therapies have become a major focus in regenerative medicine and to treat diseases. A straightforward approach combining three drugs, heparin (H), protamine (P) with ferumoxytol (F) in the form of nanocomplexes (NCs) effectively labeled stem cells for cellular MRI. We report on the physicochemical characteristics for optimizing the H, P, and F components in different ratios, and mixing sequences, producing NCs that varied in hydrodynamic size. NC size depended on the order in which drugs were mixed in media. Electron microscopy of HPF or FHP showed that F was located on the surface of spheroidal shaped HP complexes. Human stem cells incubated with FHP NCs resulted in a significantly greater iron concentration per cell compared to that found in HPF NCs with the same concentration of F. These results indicate that FHP could be useful for labeling stem cells in translational studies in the clinic. [ABSTRACT FROM AUTHOR]

Published
2017
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7. International Society for Therapeutic Ultrasound Conference 2016: Tel Aviv, Israel. 14-18 March, 2016

Author

Fowlkes, Brian, Ghanouni, Pejman, Sanghvi, Narendra, Coussios, Constantin, Lyon, Paul C., Gray, Michael, Mannaris, Christophoros, Victor, Marie de Saint, Stride, Eleanor, Cleveland, Robin, Carlisle, Robert, Wu, Feng, Middleton, Mark, Gleeson, Fergus, Aubry, Jean-Franҫois, Pauly, Kim Butts, Moonen, Chrit, Vortman, Jacob, Sharabi, Shirley, Daniels, Dianne, Last, David, Guez, David, Levy, Yoav, Volovick, Alexander, Grinfeld, Javier, Rachmilevich, Itay, Amar, Talia, Zibly, Zion, Mardor, Yael, Harnof, Sagi, Plaksin, Michael, Weissler, Yoni, Shoham, Shy, Kimmel, Eitan, Naor, Omer, Farah, Nairouz, Paeng, Dong-Guk, Xu, Zhiyuan, Snell, John, Quigg, Anders H., Eames, Matthew, Jin, Changzhu, Everstine, Ashli C., Sheehan, Jason P., Lopes, Beatriz S., Kassell, Neal, Looi, Thomas, Khokhlova, Vera, Mougenot, Charles, Hynynen, Kullervo, Drake, James, Slayton, Michael, Amodei, Richard C., Compton, Keegan, McNelly, Ashley, Latt, Daniel, Kearney, John, Melodelima, David, Dupre, Aurelien, Chen, Yao, Perol, David, Vincenot, Jeremy, Chapelon, Jean-Yves, Rivoire, Michel, Guo, Wei, Ren, Guoxin, Shen, Guofeng, Neidrauer, Michael, Zubkov, Leonid, Weingarten, Michael S., Margolis, David J., Lewin, Peter A., McDannold, Nathan, Sutton, Jonathan, Vykhodtseva, Natalia, Livingstone, Margaret, Kobus, Thiele, Zhang, Yong-Zhi, Schwartz, Michael, Huang, Yuexi, Lipsman, Nir, Jain, Jennifer, Chapman, Martin, Sankar, Tejas, Lozano, Andres, Yeung, Robert, Damianou, Christakis, Papadopoulos, Nikolaos, Brokman, Omer, Zadicario, Eyal, Brenner, Ori, Castel, David, Wu, Shih-Ying, Grondin, Julien, Zheng, Wenlan, Heidmann, Marc, Karakatsani, Maria Eleni, Sánchez, Carlos J. Sierra, Ferrera, Vincent, Konofagou, Elisa E., Yiannakou, Marinos, Cho, HongSeok, Lee, Hwayoun, Han, Mun, Choi, Jong-Ryul, Lee, Taekwan, Ahn, Sanghyun, Chang, Yongmin, Park, Juyoung, Ellens, Nicholas, Partanen, Ari, Farahani, Keyvan, Airan, Raag, Carpentier, Alexandre, Canney, Michael, Vignot, Alexandre, Lafon, Cyril, Delattre, Jean-yves, Idbaih, Ahmed, Odéen, Henrik, Bolster, Bradley, Jeong, Eun Kee, Parker, Dennis L., Gaur, Pooja, Feng, Xue, Fielden, Samuel, Meyer, Craig, Werner, Beat, Grissom, William, Marx, Michael, Weber, Hans, Taviani, Valentina, Hargreaves, Brian, Tanaka, Jun, Kikuchi, Kentaro, Ishijima, Ayumu, Azuma, Takashi, Minamihata, Kosuke, Yamaguchi, Satoshi, Nagamune, Teruyuki, Sakuma, Ichiro, Takagi, Shu, Santin, Mathieu D., Marsac, Laurent, Maimbourg, Guillaume, Monfort, Morgane, Larrat, Benoit, François, Chantal, Lehéricy, Stéphane, Tanter, Mickael, Samiotaki, Gesthimani, Wang, Shutao, Acosta, Camilo, Feinberg, Eliza R., Kovacs, Zsofia I., Tu, Tsang-Wei, Papadakis, Georgios Z., Reid, William C., Hammoud, Dima A., Frank, Joseph A., Kovacs, Zsofia i., Kim, Saejeong, Jikaria, Neekita, Bresler, Michele, Qureshi, Farhan, Xia, Jingjing, Tsui, Po-Shiang, Liu, Hao-Li, Plata, Juan C., Sveinsson, Bragi, Salgaonkar, Vasant A., Adams, Matthew, Diederich, Chris, Ozhinsky, Eugene, Bucknor, Matthew D., Rieke, Viola, Mikhail, Andrew, Severance, Lauren, Negussie, Ayele H., Wood, Bradford, de Greef, Martijn, Schubert, Gerald, Ries, Mario, Poorman, Megan E., Dockery, Mary, Chaplin, Vandiver, Dudzinski, Stephanie O., Spears, Ryan, Caskey, Charles, Giorgio, Todd, Costa, Marcia M., Papaevangelou, Efthymia, Shah, Anant, Rivens, Ian, Box, Carol, Bamber, Jeff, ter Haar, Gail, Burks, Scott R., Nagle, Matthew, Nguyen, Ben, Milo, Blerta, Le, Nhan M., Song, Shaozhen, Zhou, Kanheng, Nabi, Ghulam, Huang, Zhihong, Ben-Ezra, Shmuel, Rosen, Shani, Mihcin, Senay, Strehlow, Jan, Karakitsios, Ioannis, Le, Nhan, Schwenke, Michael, Demedts, Daniel, Prentice, Paul, Haase, Sabrina, Preusser, Tobias, Melzer, Andreas, Mestas, Jean-Louis, Chettab, Kamel, Gomez, Gustavo Stadthagen, Dumontet, Charles, Werle, Bettina, Marquet, Fabrice, Bour, Pierre, Vaillant, Fanny, Amraoui, Sana, Dubois, Rémi, Ritter, Philippe, Haïssaguerre, Michel, Hocini, Mélèze, Bernus, Olivier, Quesson, Bruno, Livneh, Amit, Adam, Dan, Robin, Justine, Arnal, Bastien, Fink, Mathias, Pernot, Mathieu, Khokhlova, Tatiana D., Schade, George R., Wang, Yak-Nam, Kreider, Wayne, Simon, Julianna, Starr, Frank, Karzova, Maria, Maxwell, Adam, Bailey, Michael R., Lundt, Jonathan E., Allen, Steven P., Sukovich, Jonathan R., Hall, Timothy, Xu, Zhen, May, Philip, Lin, Daniel W., Constans, Charlotte, Deffieux, Thomas, Aubry, Jean-Francois, Park, Eun-Joo, Ahn, Yun Deok, Kang, Soo Yeon, Park, Dong-Hyuk, Lee, Jae Young, Vidal-Jove, J., Perich, E., Ruiz, A., Jaen, A., Eres, N., del Castillo, M. Alvarez, Myers, Rachel, Kwan, James, Coviello, Christian, Rowe, Cliff, Crake, Calum, Finn, Sean, Jackson, Edward, Pouliopoulos, Antonios, Li, Caiqin, Tinguely, Marc, Tang, Meng-Xing, Garbin, Valeria, Choi, James J., Folkes, Lisa, Stratford, Michael, Nwokeoha, Sandra, Li, Tong, Farr, Navid, D’Andrea, Samantha, Gravelle, Kayla, Chen, Hong, Lee, Donghoon, Hwang, Joo Ha, Tardoski, Sophie, Ngo, Jacqueline, Gineyts, Evelyne, Roux, Jean-Pau, Clézardin, Philippe, Conti, Allegra, Magnin, Rémi, Gerstenmayer, Matthieu, Lux, François, Tillement, Olivier, Mériaux, Sébastien, Penna, Stefania Della, Romani, Gian Luca, Dumont, Erik, Sun, Tao, Power, Chanikarn, Miller, Eric, Sapozhnikov, Oleg, Tsysar, Sergey, Yuldashev, Petr V., Svet, Victor, Li, Dongli, Pellegrino, Antonio, Petrinic, Nik, Siviour, Clive, Jerusalem, Antoine, Yuldashev, Peter V., Cunitz, Bryan W., Dunmire, Barbrina, Inserra, Claude, Guedra, Matthieu, Mauger, Cyril, Gilles, Bruno, Solovchuk, Maxim, Sheu, Tony W. H., Thiriet, Marc, Zhou, Yufeng, Neufeld, Esra, Baumgartner, Christian, Payne, Davnah, Kyriakou, Adamos, Kuster, Niels, Xiao, Xu, McLeod, Helen, Dillon, Christopher, Payne, Allison, Khokhova, Vera A., Sinilshchikov, Ilya, Andriyakhina, Yulia, Rybyanets, Andrey, Shvetsova, Natalia, Berkovich, Alex, Shvetsov, Igor, Shaw, Caroline J., Civale, John, Giussani, Dino, Lees, Christoph, Ozenne, Valery, Toupin, Solenn, Salgaonkar, Vasant, Kaye, Elena, Monette, Sebastien, Maybody, Majid, Srimathveeravalli, Govindarajan, Solomon, Stephen, Gulati, Amitabh, Bezzi, Mario, Jenne, Jürgen W., Lango, Thomas, Müller, Michael, Sat, Giora, Tanner, Christine, Zangos, Stephan, Günther, Matthias, Dinh, Au Hoang, Niaf, Emilie, Bratan, Flavie, Guillen, Nicolas, Souchon, Rémi, Lartizien, Carole, Crouzet, Sebastien, Rouviere, Olivier, Han, Yang, Payen, Thomas, Palermo, Carmine, Sastra, Steve, Olive, Kenneth, van Breugel, Johanna M., van den Bosch, Maurice A., Fellah, Benjamin, Le Bihan, Denis, Hernandez-Garcia, Luis, Cain, Charles A., Lyka, Erasmia, Elbes, Delphine, Li, Chunhui, Tamano, Satoshi, Jimbo, Hayato, Yoshizawa, Shin, Fujiwara, Keisuke, Itani, Kazunori, Umemura, Shin-ichiro, Stoianovici, Dan, Zaini, Zulfadhli, Takagi, Ryo, Zong, Shenyan, Watkins, Ron, Pascal-Tenorio, Aurea, Jones, Peter, Butts-Pauly, Kim, Bouley, Donna, Chen, Yazhu, Lin, Chung-Yin, Hsieh, Han-Yi, Wei, Kuo-Chen, Garnier, Camille, Renault, Gilles, Seifabadi, Reza, Wilson, Emmanuel, Eranki, Avinash, Kim, Peter, Lübke, Dennis, Huber, Peter, Georgii, Joachim, Dresky, Caroline V., Haller, Julian, Yarmolenko, Pavel, Sharma, Karun, Celik, Haydar, Li, Guofeng, Qiu, Weibao, Zheng, Hairong, Tsai, Meng-Yen, Chu, Po-Chun, Webb, Taylor, Vyas, Urvi, Walker, Matthew, Zhong, Jidan, Waspe, Adam C., Hodaie, Mojgan, Yang, Feng-Yi, Huang, Sin-Luo, Zur, Yuval, Assif, Benny, Aurup, Christian, Kamimura, Hermes, Carneiro, Antonio A., Rothlübbers, Sven, Schwaab, Julia, Houston, Graeme, Azhari, Haim, Weiss, Noam, Sosna, Jacob, Goldberg, S. Nahum, Barrere, Victor, Jang, Kee W., Lewis, Bobbi, Wang, Xiaotong, Suomi, Visa, Edwards, David, Larrabee, Zahary, Hananel, Arik, Rafaely, Boaz, Debbiny, Rasha Elaimy, Dekel, Carmel Zeltser, Assa, Michael, Menikou, George, Mouratidis, Petros, Pineda-Pardo, José A., de Pedro, Marta Del Álamo, Martinez, Raul, Hernandez, Frida, Casas, Silvia, Oliver, Carlos, Pastor, Patricia, Vela, Lidia, Obeso, Jose, Greillier, Paul, Zorgani, Ali, Catheline, Stefan, Solovov, Vyacheslav, Vozdvizhenskiy, Michael O., Orlov, Andrew E., Wu, Chueh-Hung, Sun, Ming-Kuan, Shih, Tiffany T., Chen, Wen-Shiang, Prieur, Fabrice, Pillon, Arnaud, Cartron, Valerie, Cebe, Patrick, Chansard, Nathalie, Lafond, Maxime, Seya, Pauline Muleki, Bera, Jean-Christophe, Boissenot, Tanguy, Fattal, Elias, Bordat, Alexandre, Chacun, Helene, Guetin, Claire, Tsapis, Nicolas, Maruyama, Kazuo, Unga, Johan, Suzuki, Ryo, Fant, Cécile, Rogez, Bernadette, Afadzi, Mercy, Myhre, Ola Finneng, Vea, Siri, Bjørkøy, Astrid, Yemane, Petros Tesfamichael, van Wamel, Annemieke, Berg, Sigrid, Hansen, Rune, Angelsen, Bjørn, and Davies, Catharina

Published
2017
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8. Concerning sterile inflammation following focused ultrasound andmicrobubbles in the brain.

Author

Kovacs, Zsofia I., Burks, Scott R., and Frank, Joseph A.

Subjects
*ENCEPHALITIS, *BLOOD-brain barrier disorders, *ULTRASONIC imaging, *ENDOTHELIAL growth factors
Abstract

The article discusses sterile inflammation in brain induced by pulsed focused ultrasound (pFUS). It examines blood-brain barrier disruption (BBBD) accompanied by plasma protein extravasation into the extracellular space and role of pFUS with microbubbles (MB) in BBBD. It proposes that vascular endothelial growth factor and erythopoietin are associated with increased increased intercellular adhesion molecule-1.

Published
2017
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9. MRI and histological evaluation of pulsed focused ultrasound and microbubbles treatment effects in the brain.

Author

Kovacs ZI, Tu TW, Sundby M, Qureshi F, Lewis BK, Jikaria N, Burks SR, and Frank JA

Subjects
Animals, Histocytochemistry, Longitudinal Studies, Magnetic Resonance Imaging, Rats, Sprague-Dawley, Cerebral Cortex pathology, Cerebral Cortex radiation effects, Hippocampus pathology, Hippocampus radiation effects, Microbubbles adverse effects, Ultrasonography adverse effects
Abstract

Magnetic resonance imaging (MRI)-guided pulsed focused ultrasound (pFUS) combined with microbubbles (MB) contrast agent infusion has been shown to transiently disrupt the blood-brain barrier (BBBD), increasing the delivery of neurotherapeutics to treat central nervous system (CNS) diseases. pFUS interaction with the intravascular MB results in acoustic cavitation forces passing through the neurovascular unit (NVU), inducing BBBD detected on contrast-enhanced MRI. Multiple pFUS+MB exposures in Alzheimer's disease (AD) models are being investigated as a method to clear amyloid plaques by activated microglia or infiltrating immune cells. Since it has been reported that pFUS+MB can induce a sterile inflammatory response (SIR) [1-5] in the rat, the goal of this study was to investigate the potential long-term effects of SIR in the brain following single and six weekly sonications by serial high-resolution MRI and pathology. Methods: Female Sprague Dawley rats weighing 217±16.6 g prior to sonication received bromo-deoxyuridine (BrdU) to tag proliferating cells in the brain. pFUS was performed at 548 kHz, ultrasound burst 10 ms and initial peak negative pressure of 0.3 MPa (in water) for 120 s coupled with a slow infusion of ~460 µL/kg (5-8×10 7 MB) that started 30 s before and 30 s during sonication. Nine 2 mm focal regions in the left cortex and four regions over the right hippocampus were treated with pFUS+MB. Serial high-resolution brain MRIs at 3 T and 9.4 T were obtained following a single or during the course of six weekly pFUS+MB resulting in BBBD in the left cortex and the right hippocampus. Animals were monitored over 7 to 13 weeks and imaging results were compared to histology. Results: Fewer than half of the rats receiving a single pFUS+MB exposure displayed hypointense voxels on T2*-weighted (w) MRI at week 7 or 13 in the cortex or hippocampus without differences compared to the contralateral side on histograms of T2* maps. Single sonicated rats had evidence of limited microglia activation on pathology compared to the contralateral hemisphere. Six weekly pFUS+MB treatments resulted in pathological changes on T2*w images with multiple hypointense regions, cortical atrophy, along with 50% of rats having persistent BBBD and astrogliosis by MRI. Pathologic analysis of the multiple sonicated animals demonstrated the presence of metallophagocytic Prussian blue-positive cells in the parenchyma with significantly (p<0.05) increased areas of activated astrocytes and microglia, and high numbers of systemic infiltrating CD68 + macrophages along with BrdU + cells compared to contralateral brain. In addition, multiple treatments caused an increase in the number of hyperphosphorylated Tau (pTau)-positive neurons containing neurofibrillary tangles (NFT) in the sonicated cortex but not in the hippocampus when compared to contralateral brain, which was confirmed by Western blot (WB) (p<0.04). Conclusions: The repeated SIR following multiple pFUS+MB treatments could contribute to changes on MR imaging including persistent BBBD, cortical atrophy, and hypointense voxels on T2w and T2*w images consistent with pathological injury. Moreover, areas of astrogliosis, activated microglia, along with higher numbers of CD68 + infiltrating macrophages and BrdU + cells were detected in multiple sonicated areas of the cortex and hippocampus. Elevations in pTau and NFT were detected in neurons of the multiple sonicated cortex. Minimal changes on MRI and histology were observed in single pFUS+MB-treated rats at 7 and 13 weeks post sonication. In comparison, animals that received 6 weekly sonications demonstrated evidence on MRI and histology of vascular damage, inflammation and neurodegeneration associated with the NVU commonly observed in trauma. Further investigation is recommended of the long-term effects of multiple pFUS+MB in clinical trials., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Published
2018
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10. Focused ultrasound with microbubbles induces sterile inflammatory response proportional to the blood brain barrier opening: Attention to experimental conditions.

Author

Kovacs ZI, Burks SR, and Frank JA

Subjects
Attention, Humans, Inflammation, Permeability, Blood-Brain Barrier, Microbubbles
Abstract

This editorial highlights the findings of McMahon [1] and demonstrates the need for careful attention to experimental conditions that influence microbubble concentration and pharmacokinetics contributed to focused ultrasound-induced blood brain barrier opening and sterile inflammation.

Published
2018
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