US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening

Ai Ho Liao; Hao Li Liu; Chia Hao Su; Yu Ting Weng; Po Hung Hsu; Sheng Min Huang; Shih Yen Wu; Hsin Ell Wang; Tzu Chen Yen; Pai Chi Li

doi:10.1109/ULTSYM.2010.5935814

US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening

Ai Ho Liao^*
, Hao Li Liu
, Chia Hao Su
, Yu Ting Weng
, Po Hung Hsu
, Sheng Min Huang
, Shih Yen Wu
, Hsin Ell Wang
, Tzu Chen Yen
, Pai Chi Li

^*Corresponding author for this work

National Taiwan University
National Taiwan University of Science and Technology
Chang Gung Hospital
Chang Gung University
National Yang Ming Chiao Tung University

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

Abstract

Targeted drug delivery by magnetic resonance (MR)-guided ultrasound(US)-induced blood-brain barrier (BBB) disruption has been developed usingfocused US in combination with encapsulated gas-filled microbubbles (MBs).However, the occurrence of intracerebral hemorrhage may hamper the usefulness ofUS-induced BBB opening, which is effectively indicated by gadolinium (Gd)-basedcontrast enhancement in T₁-weighted MR scans. This paper reports thedual function of paramagnetic particles of perfluorocarbon-filledalbumin-gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) MBs for BBBopening and for distinguishing between focused-US-induced BBB opening andintracerebral hemorrhage in MR contrast images. Perfluorocarbon-filledalbumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm andconcentration of 2.903×10⁹ MBs/ml using albumin-(Gd-DTPA) andby sonication with perfluorocarbon (C₃F ₈) gas. Thealbumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated untilthe free Gd³ ions were eliminated (which were detected by xylenolorange sodium salt solution). In vitro US imaging experiments showed thatalbumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T₁-, T₂-, and T₂ ^-weighted MR images.The r₁ and r₂ relaxivities for Gd-DTPA were 7.69 and 21.35s¹ mM¹, respectively, indicating that the MBs represent apositive contrast agent in T ₁-weighted images. In vivo MR imagingexperiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA)MBs can be used to both induce and detect disruption of the BBB. Afterdisrupting the BBB, the leakage of albumin-(Gd-DTPA) MBs shells can be detectedfor distinguishing between focused-US-induced disruption of the BBB andintracerebral hemorrhage in T ₁-weighted images. The results indicatethat albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrastagent for BBB opening and differentiating focused-US-induced BBB opening fromintracerebral hemorrhage.

Original language	English
Title of host publication	2010 IEEE International Ultrasonics Symposium, IUS 2010
Pages	1015-1018
Number of pages	4
DOIs	https://doi.org/10.1109/ULTSYM.2010.5935814
State	Published - 2010
Event	2010 IEEE International Ultrasonics Symposium, IUS 2010 - San Diego, CA, United States Duration: 11 10 2010 → 14 10 2010

Publication series

Name	Proceedings - IEEE Ultrasonics Symposium
ISSN (Print)	1051-0117

Conference

Conference	2010 IEEE International Ultrasonics Symposium, IUS 2010
Country/Territory	United States
City	San Diego, CA
Period	11/10/10 → 14/10/10

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10.1109/ULTSYM.2010.5935814

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Liao, A. H., Liu, H. L., Su, C. H., Weng, Y. T., Hsu, P. H., Huang, S. M., Wu, S. Y., Wang, H. E., Yen, T. C., & Li, P. C. (2010). US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening. In 2010 IEEE International Ultrasonics Symposium, IUS 2010 (pp. 1015-1018). Article 5935814 (Proceedings - IEEE Ultrasonics Symposium). https://doi.org/10.1109/ULTSYM.2010.5935814

@inproceedings{4544c52b468343cc9a7263a2e06a2993,

title = "US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening",

abstract = "Targeted drug delivery by magnetic resonance (MR)-guided ultrasound(US)-induced blood-brain barrier (BBB) disruption has been developed usingfocused US in combination with encapsulated gas-filled microbubbles (MBs).However, the occurrence of intracerebral hemorrhage may hamper the usefulness ofUS-induced BBB opening, which is effectively indicated by gadolinium (Gd)-basedcontrast enhancement in T1-weighted MR scans. This paper reports thedual function of paramagnetic particles of perfluorocarbon-filledalbumin-gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) MBs for BBBopening and for distinguishing between focused-US-induced BBB opening andintracerebral hemorrhage in MR contrast images. Perfluorocarbon-filledalbumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm andconcentration of 2.903{\texttimes}109 MBs/ml using albumin-(Gd-DTPA) andby sonication with perfluorocarbon (C3F 8) gas. Thealbumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated untilthe free Gd3 ions were eliminated (which were detected by xylenolorange sodium salt solution). In vitro US imaging experiments showed thatalbumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2-, and T2 -weighted MR images.The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35s1 mM1, respectively, indicating that the MBs represent apositive contrast agent in T 1-weighted images. In vivo MR imagingexperiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA)MBs can be used to both induce and detect disruption of the BBB. Afterdisrupting the BBB, the leakage of albumin-(Gd-DTPA) MBs shells can be detectedfor distinguishing between focused-US-induced disruption of the BBB andintracerebral hemorrhage in T 1-weighted images. The results indicatethat albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrastagent for BBB opening and differentiating focused-US-induced BBB opening fromintracerebral hemorrhage.",

author = "Liao, \{Ai Ho\} and Liu, \{Hao Li\} and Su, \{Chia Hao\} and Weng, \{Yu Ting\} and Hsu, \{Po Hung\} and Huang, \{Sheng Min\} and Wu, \{Shih Yen\} and Wang, \{Hsin Ell\} and Yen, \{Tzu Chen\} and Li, \{Pai Chi\}",

year = "2010",

doi = "10.1109/ULTSYM.2010.5935814",

language = "英语",

isbn = "9781457703829",

series = "Proceedings - IEEE Ultrasonics Symposium",

pages = "1015--1018",

booktitle = "2010 IEEE International Ultrasonics Symposium, IUS 2010",

note = "2010 IEEE International Ultrasonics Symposium, IUS 2010 ; Conference date: 11-10-2010 Through 14-10-2010",

}

Liao, AH, Liu, HL, Su, CH, Weng, YT, Hsu, PH, Huang, SM, Wu, SY, Wang, HE, Yen, TC & Li, PC 2010, US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening. in 2010 IEEE International Ultrasonics Symposium, IUS 2010., 5935814, Proceedings - IEEE Ultrasonics Symposium, pp. 1015-1018, 2010 IEEE International Ultrasonics Symposium, IUS 2010, San Diego, CA, United States, 11/10/10. https://doi.org/10.1109/ULTSYM.2010.5935814

US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening. / Liao, Ai Ho; Liu, Hao Li; Su, Chia Hao et al.
2010 IEEE International Ultrasonics Symposium, IUS 2010. 2010. p. 1015-1018 5935814 (Proceedings - IEEE Ultrasonics Symposium).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

TY - GEN

T1 - US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening

AU - Liao, Ai Ho

AU - Liu, Hao Li

AU - Su, Chia Hao

AU - Weng, Yu Ting

AU - Hsu, Po Hung

AU - Huang, Sheng Min

AU - Wu, Shih Yen

AU - Wang, Hsin Ell

AU - Yen, Tzu Chen

AU - Li, Pai Chi

PY - 2010

Y1 - 2010

N2 - Targeted drug delivery by magnetic resonance (MR)-guided ultrasound(US)-induced blood-brain barrier (BBB) disruption has been developed usingfocused US in combination with encapsulated gas-filled microbubbles (MBs).However, the occurrence of intracerebral hemorrhage may hamper the usefulness ofUS-induced BBB opening, which is effectively indicated by gadolinium (Gd)-basedcontrast enhancement in T1-weighted MR scans. This paper reports thedual function of paramagnetic particles of perfluorocarbon-filledalbumin-gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) MBs for BBBopening and for distinguishing between focused-US-induced BBB opening andintracerebral hemorrhage in MR contrast images. Perfluorocarbon-filledalbumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm andconcentration of 2.903×109 MBs/ml using albumin-(Gd-DTPA) andby sonication with perfluorocarbon (C3F 8) gas. Thealbumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated untilthe free Gd3 ions were eliminated (which were detected by xylenolorange sodium salt solution). In vitro US imaging experiments showed thatalbumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2-, and T2 -weighted MR images.The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35s1 mM1, respectively, indicating that the MBs represent apositive contrast agent in T 1-weighted images. In vivo MR imagingexperiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA)MBs can be used to both induce and detect disruption of the BBB. Afterdisrupting the BBB, the leakage of albumin-(Gd-DTPA) MBs shells can be detectedfor distinguishing between focused-US-induced disruption of the BBB andintracerebral hemorrhage in T 1-weighted images. The results indicatethat albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrastagent for BBB opening and differentiating focused-US-induced BBB opening fromintracerebral hemorrhage.

AB - Targeted drug delivery by magnetic resonance (MR)-guided ultrasound(US)-induced blood-brain barrier (BBB) disruption has been developed usingfocused US in combination with encapsulated gas-filled microbubbles (MBs).However, the occurrence of intracerebral hemorrhage may hamper the usefulness ofUS-induced BBB opening, which is effectively indicated by gadolinium (Gd)-basedcontrast enhancement in T1-weighted MR scans. This paper reports thedual function of paramagnetic particles of perfluorocarbon-filledalbumin-gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) MBs for BBBopening and for distinguishing between focused-US-induced BBB opening andintracerebral hemorrhage in MR contrast images. Perfluorocarbon-filledalbumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm andconcentration of 2.903×109 MBs/ml using albumin-(Gd-DTPA) andby sonication with perfluorocarbon (C3F 8) gas. Thealbumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated untilthe free Gd3 ions were eliminated (which were detected by xylenolorange sodium salt solution). In vitro US imaging experiments showed thatalbumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2-, and T2 -weighted MR images.The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35s1 mM1, respectively, indicating that the MBs represent apositive contrast agent in T 1-weighted images. In vivo MR imagingexperiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA)MBs can be used to both induce and detect disruption of the BBB. Afterdisrupting the BBB, the leakage of albumin-(Gd-DTPA) MBs shells can be detectedfor distinguishing between focused-US-induced disruption of the BBB andintracerebral hemorrhage in T 1-weighted images. The results indicatethat albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrastagent for BBB opening and differentiating focused-US-induced BBB opening fromintracerebral hemorrhage.

UR - https://www.scopus.com/pages/publications/80054075984

U2 - 10.1109/ULTSYM.2010.5935814

DO - 10.1109/ULTSYM.2010.5935814

M3 - 会议稿件

AN - SCOPUS:80054075984

SN - 9781457703829

T3 - Proceedings - IEEE Ultrasonics Symposium

SP - 1015

EP - 1018

BT - 2010 IEEE International Ultrasonics Symposium, IUS 2010

T2 - 2010 IEEE International Ultrasonics Symposium, IUS 2010

Y2 - 11 October 2010 through 14 October 2010

ER -

US/MRI dual modality contrast agent for concurrent MR and ultrasonicimaging of focused-ultrasound induced blood-brian barrier opening

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