Hemorrhage Detection During Focused-Ultrasound Induced Blood-Brain-Barrier Opening by Using Susceptibility-Weighted Magnetic Resonance Imaging

Liu, Hao-Li; Wai, Yau‐Yau; Chen, Wen-Shiang; Chen, Jin-Chung; Hsu, Peng Wei; Wu, Xinyu; Huang, Wei-Chen; Yen, Tzu‐Chen; Wang, Jiun‐Jie

doi:10.1016/j.ultrasmedbio.2008.01.011

Cited by 128 publications

(116 citation statements)

References 22 publications

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“…5), the major drawback of focus-ultrasound BBB opening. The safety threshold identified in our study is in keeping with previous findings (12). Pressures lower than or equal to 1.1 MPa may occasionally cause erythrocyte extravasation without gross hemorrhage (12).…”

Section: Discussionsupporting

confidence: 92%

“…The safety threshold identified in our study is in keeping with previous findings (12). Pressures lower than or equal to 1.1 MPa may occasionally cause erythrocyte extravasation without gross hemorrhage (12). Notably, we have shown that the use of SPIOenhanced T2*-weighted imaging has the potential to distinguish between erythrocyte extravasation and hemorrhage, an important issue in the imaging of BBB opening (12).…”

Section: Discussionsupporting

confidence: 90%

“…Previous research has shown the usefulness of fully flow-compensated T2*-weighted sequences to detect brain hemorrhage induced by focused ultrasound (12). Notably, this method has been widely used for detecting hemorrhage in several disease conditions, including arteriovenous malformations.…”

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confidence: 99%

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Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: Usefulness for distinguishing between focused ultrasound‐induced blood–brain barrier disruption and brain hemorrhage

Liu

Hsu

Chu

et al. 2008

Magnetic Resonance Imaging

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Purpose:To investigate the usefulness of a fully flow-compensated heavy T2*-weighted imaging enhanced by superparamagnetic iron oxide (SPIO) particles for distinguishing between focused ultrasound-induced disruption of bloodbrain barrier (BBB) and brain hemorrhage. Materials and Methods:Focused ultrasound (frequency: 1.5 MHz) was used to induce disruption of the BBB in 39 rats. Two T2*-weighted images were obtained before and after SPIO administration. Preenhanced T2*-weighted images were used to detect hemorrhage. Detection of BBB disruption was performed on SPIO-enhanced images. Thirty-four rats were sacrificed after magnetic resonance (MR) scanning for histological confirmation of brain lesions. Theremaining five animals were followed up for 35 days.Prussian blue staining was performed on histological sections to detect SPIO particles in the brain. Results:After SPIO injection the areas of BBB disruption in rat brain were significantly enlarged. The area of mismatch between the T2*-weighted images indicated a safe region where BBB opening occurred without hemorrhagic complications. In the longitudinal study, removal of SPIO occurred at a faster rate in hemorrhagic areas, albeit being closer to that occurring in the liver. The presence of SPIO was confirmed by Prussian blue staining in brain parenchyma and capillary endothelial cells in areas of BBB disruption.Conclusion: T2*-weighted images-either with and without SPIO enhancement-may differentiate focused ultrasound-induced BBB disruption from brain hemorrhage.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

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Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: Usefulness for distinguishing between focused ultrasound‐induced blood–brain barrier disruption and brain hemorrhage

Liu

Hsu

Chu

et al. 2008

Magnetic Resonance Imaging

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“…Indeed, FUS sonication could damage the brain tissue via FUS-induced edema, hemorrhage, ischemia, and apoptosis (10,18,19). To minimize brain damage, recent studies have focused on optimizing FUS parameters combined with intravascular preformed microbubbles to minimize sonication-induced hemorrhage (5,6,9,20,21).…”

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confidence: 99%

“…To minimize brain damage, recent studies have focused on optimizing FUS parameters combined with intravascular preformed microbubbles to minimize sonication-induced hemorrhage (5,6,9,20,21). To ensure safe operation, the role of MRI becomes even more important; MRI not only aids FUS to localize the target region to gauge the BBB disruption but also provides simultaneous monitoring to detect incipient hemorrhage or neuronal dysfunction (18,22).…”

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confidence: 99%

Detecting blood–brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: A correlation study with contrast‐enhanced MRI

Weng

Lin

et al. 2010

Magnetic Resonance in Med

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Focused ultrasound combined with an intravascular ultrasound contrast agent can induce transient disruption of the blood-brain barrier, and the blood-brain barrier disruption can be detected by contrast-enhanced MRI. There is, however, no study investigating the ability of various MR methods to detect focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage. Sonication was applied to 15 rat brains with four different doses of ultrasound contrast agent (0, 10, 30, or 50 mL/kg), and contrast-enhanced T1-weighted spin echo, gradient echo images, and longitudinal relaxation rate mapping along with effective transverse relaxation time-weighted and susceptibility-weighted images were acquired. Volume-of-interest-based and threshold-based analyses were performed to quantify the contrast enhancement, which was then correlated with the ultrasound contrast agent dose and with the amount of Evans blue extravasation. Both effective transverse relaxation time-weighted and susceptibility-weighted images did not detect histology-proved intracranial hemorrhage at 10 mL/kg, but MRI failed to detect mild intracranial hemorrhage at 30 mL/kg. All tested sequences showed detectable contrast enhancement increasing with ultrasound contrast agent dose. In correlating with Evans blue extravasation, the gradient echo sequence was slightly better than the spin echo sequence and was comparable to longitudinal relaxation rate mapping. In conclusion, both gradient echo and spin echo sequences were all reliable in indicating the degree of focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage. Magn Reson Med 65:802-811, 2011. V C 2010 Wiley-Liss, Inc.Key words: magnetic resonance imaging; focused ultrasound; blood-brain barrier; ultrasound contrast agent; microbubbles; R 1 mappingThe blood-brain barrier (BBB) results from the selectivity of the tight junctions between endothelial cells in central nervous system vessels. It limits the passage of most potential diagnostically and therapeutically useful molecules from circulation into the brain parenchyma and precludes their use in diagnosis or treatment in the central nervous system (1-3). Recently, focused ultrasound (FUS) combined with intravascular ultrasound contrast agent (UCA) has been shown to transiently increase the transport of molecules across the BBB (4-7). This increase in BBB permeability can be detected by contrast-enhanced MRI using gadolinium-based (8,9) or iron oxide-based contrast agents (10) or by single-photon emission computed tomography with 99m Tc-based radiotracers (11). Using these imaging methods to guide FUS sonication, BBB at the targeted brain regions can be disrupted accurately, facilitating the delivery of diagnostic or therapeutic agents (12)(13)(14)(15)(16)(17).Although FUS sonication is promising in facilitating drug delivery across BBB, increasing concerns have been raised regarding its potential adverse effects on the brain. Indeed, FUS sonication could damage the brain tissue via FUS-induced edema, hem...

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Triculture Model of In Vitro BBB and its Application to Study BBB‐Associated Chemosensitivity and Drug Delivery in Glioblastoma

Seo

Nah

Lee

et al. 2021

Adv Funct Materials

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Physiologically, brain tumors interact with surrounding vascular and glial cells, and change their responses to survive in brain tissue‐specific microenvironments. A major difficulty in brain tumor treatment is caused by the organism's high resistance to pharmaceutical drugs and poor blood–brain barrier (BBB) penetration. Therefore, mimicking the physiological environment of brain tumors on in vitro platforms can aid in predicting the cellular response to drugs. Here, an engineered 3D human glioblastoma in vitro platform that is integrated with a tricultured BBB is presented. First, the barrier function of the constructed BBB model and its reversibility are characterized, after administrating BBB‐opening agents through the microvasculature. The brain tumor cells that are cocultured in the BBB show a more aggressive growth pattern and high drug resistance, as well as secreting high concentrations of inflammatory cytokines. Finally, the delivery of BBB‐nonpenetrating drugs are promoted by chemically opening the BBB. The results of this study indicate that the platform can potentially study the physiology of the BBB, and monitor drug responses based on the interaction of the brain tumor and BBB.

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Hemorrhage Detection During Focused-Ultrasound Induced Blood-Brain-Barrier Opening by Using Susceptibility-Weighted Magnetic Resonance Imaging

Cited by 128 publications

References 22 publications

Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: Usefulness for distinguishing between focused ultrasound‐induced blood–brain barrier disruption and brain hemorrhage

Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: Usefulness for distinguishing between focused ultrasound‐induced blood–brain barrier disruption and brain hemorrhage

Detecting blood–brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: A correlation study with contrast‐enhanced MRI

Triculture Model of In Vitro BBB and its Application to Study BBB‐Associated Chemosensitivity and Drug Delivery in Glioblastoma

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