scholarly journals Early treatment of HER2-amplified brain tumours with targeted nk-92 cells and focused ultrasound improves survival

2015 ◽  
Vol 42 (S1) ◽  
pp. S11-S11
Author(s):  
RD Alkins ◽  
A Burgess ◽  
R Kerbel ◽  
WS Wels ◽  
K Hynynen
Keyword(s):  
Brain Tumours ◽  
Focused Ultrasound ◽  
Transcranial Ultrasound ◽  
Adjuvant Chemoradiotherapy ◽  
Her2 Receptor ◽  
Non Invasive ◽  
Dismal Prognosis ◽  
Cancer Line ◽  
Treatment Paradigm ◽  
Epithelial Tumours

Background: Malignant brain tumors have a dismal prognosis, with residual after surgery necessitating adjuvant chemoradiotherapy. We previously demonstrated that targeted Natural Killer (NK-92) cells could be delivered to the brain using a combination of MRI-guided focused ultrasound and Definity microbubbles. Once in the CNS, they can track to malignant tissues without inflicting collateral damage. The HER2 receptor is expressed by epithelial tumours including both breast and glioblastoma; breast tumors with HER2-amplification have a higher risk of CNS metastasis, and poorer prognosis. Methods: We investigated whether multiple combined treatments of targeted NK-92 cells and focused ultrasound with microbubbles could slow tumour growth and improve survival in an orthotopic HER2-amplified rodent brain tumour model using a human breast cancer line as a prototype. Results: Early daily treatments with targeted NK-92 cells and ultrasound improved survival and decreased tumour volumes compared with bi-weekly treatments, or either treatment alone. The intensive treatment paradigm resulted in cure in 50% of subjects. Conclusions: Many tumour proteins could be exploited for targeted therapy with the NK-92 cell line, and combined with the mounting safety evidence for transcranial ultrasound, this may soon provide a non-invasive and highly targeted treatment option for patients with brain tumours.

scholarly journals Offline impact of transcranial focused ultrasound on cortical activation in primates

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Lennart Verhagen ◽  
Cécile Gallea ◽  
Davide Folloni ◽  
Charlotte Constans ◽  
Daria EA Jensen ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Brain Regions ◽  
Cortical Activation ◽  
Transcranial Ultrasound ◽  
Full Potential ◽  
Non Invasive ◽  
Specific Effects ◽  
Ultrasound Stimulation ◽  
Induced Signal ◽  
Stimulation Technique

To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting ‘offline’ changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS caused stimulated areas to interact more selectively with the rest of the brain. In a within-subject design, we observe regionally specific TUS effects for two medial frontal brain regions – supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.

scholarly journals Offline impact of transcranial focused ultrasound on cortical activation in primates

2018 ◽  
Author(s):  
Lennart Verhagen ◽  
Cécile Gallea ◽  
Davide Folloni ◽  
Charlotte Constans ◽  
Daria EA Jensen ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Brain Regions ◽  
Cortical Activation ◽  
Transcranial Ultrasound ◽  
Full Potential ◽  
Non Invasive ◽  
Specific Effects ◽  
Brain Circuits ◽  
Induced Signal ◽  
Stimulation Technique

AbstractTo understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound (TUS) is a promising non-invasive brain stimulation technique. To date, investigations have focused on short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting ‘offline’ changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 seconds of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS’ impact can be demonstrated by showing such patterns change for stimulated areas. We report regionally specific TUS effects for two medial frontal brain regions – supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.

scholarly journals Potential intracranial applications of magnetic resonance–guided focused ultrasound surgery

2013 ◽  
Vol 118 (2) ◽  
pp. 215-221 ◽  
Author(s):  
Stephen Monteith ◽  
Jason Sheehan ◽  
Ricky Medel ◽  
Max Wintermark ◽  
Matthew Eames ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Focused Ultrasound ◽  
Focal Point ◽  
Accurate Method ◽  
Transcranial Ultrasound ◽  
Ultrasound Surgery ◽  
Focused Ultrasound Surgery ◽  
High Resolution Mri ◽  
Treatment Paradigm ◽  
High Doses

Magnetic resonance–guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

scholarly journals Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonios N. Pouliopoulos ◽  
Nancy Kwon ◽  
Greg Jensen ◽  
Anna Meaney ◽  
Yusuke Niimi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Safety Profile ◽  
Focused Ultrasound ◽  
Multiple Case Study ◽  
Brain Barrier ◽  
Non Invasive ◽  
Blood Brain ◽  
Multiple Case ◽  
Bbb Opening

AbstractAn emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood–brain barrier (BBB) in a non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.

scholarly journals Updated Costs of Uterine Fibroid Treatments Including Focused Ultrasound Surgery

2018 ◽  
Author(s):  
Bijan J. Borah ◽  
Elizabeth A. Stewart
Keyword(s):  
Magnetic Resonance ◽  
Focused Ultrasound ◽  
Treatment Options ◽  
Uterine Fibroids ◽  
Reproductive Age ◽  
Invasive Treatment ◽  
Ultrasound Surgery ◽  
Non Invasive ◽  
Focused Ultrasound Surgery ◽  
Reproductive Age Women

Uterine leiomyomas (fibroids) affect 20–40% of reproductive age women and are the major indication for hysterectomy. Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a new, potentially disruptive, non-invasive and uterine-sparing treatment option that has been shown to yield similar or better clinical outcomes than other uterine-sparing interventions. However, the costs of MRgFUS and other minimally-invasive treatment options have not been studied using US practice data. This study attempts to fill this void. And since uterine fibroids are the first FDA-approved indication for MRgFUS treatment, this study may also have implications for other indications which are now investigational.

scholarly journals Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy: The Next Step in the Treatment of Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Brian Keller ◽  
Anna M. E. Bruynzeel ◽  
Chad Tang ◽  
Anand Swaminath ◽  
Linda Kerkmeijer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Oncologic Outcomes ◽  
Invasive Treatment ◽  
Non Invasive ◽  
Treatment Paradigm ◽  
Plan Adaptation ◽  
New Treatment ◽  
Tissue Sparing

Adaptive MR-guided radiotherapy (MRgRT) is a new treatment paradigm and its role as a non-invasive treatment option for renal cell carcinoma is evolving. The early clinical experience to date shows that real-time plan adaptation based on the daily MRI anatomy can lead to improved target coverage and normal tissue sparing. Continued technological innovations will further mitigate the challenges of organ motion and enable more advanced treatment adaptation, and potentially lead to enhanced oncologic outcomes and preservation of renal function. Future applications look promising to make a positive clinical impact and further the personalization of radiotherapy in the management of renal cell carcinoma.

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