MR-Guided Focused Ultrasound for Brain Tumors

2021 ◽  
pp. 415-427
Author(s):  
Ying Meng ◽  
Christopher B. Pople ◽  
Suganth Suppiah ◽  
Nir Lipsman
Keyword(s):  
Brain Tumors ◽  
Focused Ultrasound

scholarly journals Focused ultrasound in neuro-oncology: the role of the Focused Ultrasound Foundation in driving adoption and innovation

2021 ◽  
Author(s):  
Emily C. Whipple ◽  
Camille A. Favero ◽  
Neal F. Kassell
Keyword(s):  
Drug Delivery ◽  
Brain Tumors ◽  
Focused Ultrasound ◽  
Clinical Evidence ◽  
Neurological Injury ◽  
High Concentration ◽  
Potential Applications ◽  
Tumor Agent

Abstract Introduction Intra-arterial (lA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated lA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of lA therapy for the treatment of brain tumors and refinement of its potential applications are necessary. Methods We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSJACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of lA therapy for the treatment of brain tumors. Results Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the lA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy. Conclusion lA drug delivery may significantly affect the way treatment are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of lA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, lA therapy may offer significant benefits for the treatment of brain tumors.

scholarly journals Focused Ultrasound Strategies for Brain Tumor Therapy

2019 ◽  
Vol 19 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Adomas Bunevicius ◽  
Nathan Judson McDannold ◽  
Alexandra J Golby
Keyword(s):  
Brain Tumors ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Drug Distribution ◽  
Low Frequency ◽  
Tissue Level ◽  
Chemotherapeutic Agents ◽  
Promising Tool ◽  
Investigational Agents

Abstract BACKGROUND A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood–brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors. OBJECTIVE To review the mechanism of FUS, preclinical evidence, and clinical studies that used low-frequency FUS for a BBB opening in gliomas. METHODS Literature review. RESULTS The potential of externally delivered low-intensity ultrasound for a temporally and spatially precise and predictable disruption of the BBB has been investigated for over a decade, yielding extensive preclinical literature demonstrating that FUS can disrupt the BBB in a spatially targeted and temporally reversible manner. Studies in animal models documented that FUS enhanced the delivery of numerous chemotherapeutic and investigational agents across the BBB and into brain tumors, including temozolomide, bevacizumab, 1,3-bis (2-chloroethyl)-1-nitrosourea, doxorubicin, viral vectors, and cells. Chemotherapeutic interventions combined with FUS slowed tumor progression and improved animal survival. Recent advances of MRgFUS systems allow precise, temporally and spatially controllable, and safe transcranial delivery of ultrasound energy. Initial clinical evidence in glioma patients has shown the efficacy of MRgFUS in disrupting the BBB, as demonstrated by an enhanced gadolinium penetration. CONCLUSION Thus far, a temporary disruption of the BBB followed by the administration of chemotherapy has been both feasible and safe. Further studies are needed to determine the actual drug delivery, including the drug distribution at a tissue-level scale, as well as effects on tumor growth and patient prognosis.

Modeling of intensity-modulated focused ultrasound in pediatric brain tumors using acoustic holograms

2021 ◽  
Author(s):  
Sergio Jimenez-Gambin ◽  
Antonios N. Pouliopoulos ◽  
Zachary K. Englander ◽  
Noe Jimenez ◽  
Francisco Camarena ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Focused Ultrasound ◽  
Pediatric Brain Tumors ◽  
Intensity Modulated ◽  
Pediatric Brain

scholarly journals Pharmacodynamic Analysis of Magnetic Resonance Imaging-Monitored Focused Ultrasound-Induced Blood-Brain Barrier Opening for Drug Delivery to Brain Tumors

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Po-Chun Chu ◽  
Wen-Yen Chai ◽  
Han-Yi Hsieh ◽  
Jiun-Jie Wang ◽  
Shiaw-Pyng Wey ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Small Molecule ◽  
Focused Ultrasound ◽  
Therapeutic Agents ◽  
Tumor Treatment ◽  
Target Region ◽  
Pharmacodynamic Analysis ◽  
The Brain ◽  
Bbb Opening

Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors.

scholarly journals BOT-01 BLOOD-BRAIN BARRIER OPENING USING 220-KHZ TRANSCRANIAL MRI-GUIDED FOCUSED ULTRASOUND AND MICROBUBBLES IN MOUSE AND RAT

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii12-ii12
Author(s):  
Michiharu Yoshida ◽  
Kazuo Maruyama ◽  
Yasutaka Kato ◽  
Rachmilevitch Itay ◽  
Syuji Suzuki ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Maximum Temperature ◽  
Non Invasive ◽  
Therapeutic Drugs ◽  
Blood Brain ◽  
Mri Guided ◽  
Bbb Opening

Abstract OBJECTIVE In neuro-oncology, it is believed that one major obstacle to effective chemotherapy is the high vascularity and heterogenous permeability of brain tumors. Focused ultrasound (FUS) exposure with the microbubbles has been shown to transiently open the blood-brain barrier (BBB) without depositing thermal energy, and thus may enhance the delivery of various therapeutic drugs into brain tumors. The aim of this study was to evaluate the BBB opening using 220-kHz transcranial MRI-guided FUS (TcMRgFUS) device and microbubbles in mouse and rat. METHODS The experiments were performed with the 220-kHz ExAblate Neuro TcMRgFUS system (InSightec) and novel lipid bubbles (LB, Teikyo Univ.). Normal mouse and rat brains were irradiated with TcMRgFUS (output power, 5W; duration of irradiation, 30 s; duty cycle 100%) following intravenous injection of 6x107 LB per mouse and rat, respectively. On irradiation, target temperature rise & cavitation signal were monitored by MR thermometry and cavitation receiver, respectively. Immediately after irradiation, BBB opening and complications were detected based on T1, T2, T2*, and Gadolinium (Gd) enhanced T1-weighted images. RESULTS The maximum temperature of brain tissue was under 42 C. There were no risky-cavitation signals causing hemorrhage. The FUS-LB exposure induced successful BBB opening effect in both mouse and rat, confirmed by Gd enhancement in the target region, lateral ventricles, and sulcus. In addition, there were no complications such as edema, coagulation, and hemorrhage. CONCLUSIONS Although there remain many conditions to be optimized, BBB opening using a 220-kHz TcMRgFUS device and LB can offer a non-invasive and feasible drug delivery for brain malignancies.

Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial

1991 ◽  
Vol 10 (3) ◽  
Author(s):  
A.N. Guthkelch ◽  
L.P. Carter ◽  
J.R. Cassady ◽  
K.H. Hynynen ◽  
R.P. Iacono ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Phase I ◽  
Phase I Trial ◽  
Focused Ultrasound ◽  
Malignant Brain Tumors ◽  
Ultrasound Hyperthermia

scholarly journals Non-invasive focused ultrasound-based synergistic treatment of brain tumors

2016 ◽  
Vol 3 (3) ◽  
pp. 63-68 ◽  
Author(s):  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
Chiung-Yin Huang ◽  
Kuo-Chen Wei
Keyword(s):  
Brain Tumors ◽  
Focused Ultrasound ◽  
Non Invasive
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