scholarly journals Acoustic feedback enables safe and reliable carboplatin delivery across the blood-brain barrier with a clinical focused ultrasound system and improves survival in a rat glioma model

Theranostics ◽  
2019 ◽  
Vol 9 (21) ◽  
pp. 6284-6299 ◽  
Author(s):  
Nathan McDannold ◽  
Yongzhi Zhang ◽  
Jeffrey G. Supko ◽  
Chanikarn Power ◽  
Tao Sun ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Rat Glioma ◽  
Acoustic Feedback ◽  
Blood Brain ◽  
Ultrasound System ◽  
Glioma Model

scholarly journals DDEL-13. FOCUSED ULTRASOUND MEDIATED BLOOD BRAIN BARRIER DISRUPTION IN A MURINE MODEL OF PONTINE GLIOMA: A SAFETY AND FEASIBILITY STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii286-iii286
Author(s):  
Zachary Englander ◽  
Hong-Jian Wei ◽  
Antonios Pouliopoulos ◽  
Pavan Upadhyayula ◽  
Chia-Ing Jan ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Center Frequency ◽  
Single Element ◽  
Pontine Glioma ◽  
Orthotopic Model ◽  
Function Generator ◽  
Blood Brain ◽  
Glioma Model

Abstract BACKGROUND Drug delivery remains a major obstacle in DIPG, as the blood brain barrier (BBB) limits the penetration of systemic therapies to the brainstem. Focused ultrasound (FUS) is an exciting new technology that, when combined with microbubbles, can open the BBB permitting the entry of drugs across the cerebrovasculature. Given that the utility of FUS in brainstem tumors remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. METHODS A syngeneic orthotopic model was established by stereotactic injection of PDGF-B+PTEN-/-p53-/- murine glioma cells (10,000/1ul) into the pons of B6 albino mice. A single-element, spherical-segment FUS transducer (center frequency=1.5MHz) driven by a function generator through a power amplifier (acoustic pressure=0.7MPa) was used with concurrent intravenous microbubble injection (FUS+MB) to sonicate the tumor on post-injection day 14. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen (KIS) testing was completed to measure motor function. Mice were either immediately sacrificed for histopathological assessment or serially monitored for survival. RESULTS In mice treated with FUS (n=11), there was no measured deficit in KIS testing. Additionally, the degree of intra-tumoral hemorrhage and inflammation on H&E in control (n=5) and treated mice (n=5) was similar. Lastly, there was no difference in survival between the groups (control, n=6, median=26 days; FUS, n=6, median=25 days, p>0.05). CONCLUSION FUS+MB is a safe and feasible technique to open the BBB in a preclinical pontine glioma model.

A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model

1985 ◽  
Vol 67 (1-2) ◽  
pp. 96-102 ◽  
Author(s):  
P. A. Stewart ◽  
K. Hayakawa ◽  
E. Hayakawa ◽  
C. L. Farrell ◽  
R. F. Del Maestro
Keyword(s):  
Blood Brain Barrier ◽  
Quantitative Study ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Rat Glioma ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Glioma Model

scholarly journals Focused ultrasound mediated blood–brain barrier opening is safe and feasible in a murine pontine glioma model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zachary K. Englander ◽  
Hong-Jian Wei ◽  
Antonios N. Pouliopoulos ◽  
Ethan Bendau ◽  
Pavan Upadhyayula ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Motor Function ◽  
Focused Ultrasound ◽  
Weight Lifting ◽  
Brain Barrier ◽  
Single Element ◽  
Pontine Glioma ◽  
Blood Brain ◽  
Glioma Model ◽  
Bbb Opening

AbstractDrug delivery in diffuse intrinsic pontine glioma is significantly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), when combined with the administration of microbubbles can effectively open the BBB permitting the entry of drugs across the cerebrovasculature into the brainstem. Given that the utility of FUS in brainstem malignancies remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. A syngeneic orthotopic model was developed by stereotactic injection of PDGF-B+PTEN−/−p53−/− murine glioma cells into the pons of B6 mice. A single-element, spherical-segment 1.5 MHz ultrasound transducer driven by a function generator through a power amplifier was used with concurrent intravenous microbubble injection for tumor sonication. Mice were randomly assigned to control, FUS and double-FUS groups. Pulse and respiratory rates were continuously monitored during treatment. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen testing and sequential weight lifting measured motor function before and after sonication. A subset of animals were treated with etoposide following ultrasound. Mice were either sacrificed for tissue analysis or serially monitored for survival with daily weights. FUS successfully caused BBB opening while preserving normal cardiorespiratory and motor function. Furthermore, the degree of intra-tumoral hemorrhage and inflammation on H&E in control and treated mice was similar. There was also no difference in weight loss and survival between the groups (p > 0.05). Lastly, FUS increased intra-tumoral etoposide concentration by more than fivefold. FUS is a safe and feasible technique for repeated BBB opening and etoposide delivery in a preclinical pontine glioma model.

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