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

^*此作品的通信作者

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

研究成果: 圖書/報告稿件的類型 › 會議稿件 › 同行評審

摘要

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.

原文	英語
主出版物標題	2010 IEEE International Ultrasonics Symposium, IUS 2010
頁面	1015-1018
頁數	4
DOIs	https://doi.org/10.1109/ULTSYM.2010.5935814
出版狀態	已出版 - 2010
事件	2010 IEEE International Ultrasonics Symposium, IUS 2010 - San Diego, CA, 美國持續時間: 11 10 2010 → 14 10 2010

出版系列

名字	Proceedings - IEEE Ultrasonics Symposium
ISSN（列印）	1051-0117

Conference

Conference	2010 IEEE International Ultrasonics Symposium, IUS 2010
國家/地區	美國
城市	San Diego, CA
期間	11/10/10 → 14/10/10

存取文件

10.1109/ULTSYM.2010.5935814

其它文件與鏈接

Link to publication in Scopus

引用此

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. 於 2010 IEEE International Ultrasonics Symposium, IUS 2010 (頁 1015-1018). 文章 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. 於 2010 IEEE International Ultrasonics Symposium, IUS 2010., 5935814, Proceedings - IEEE Ultrasonics Symposium, 頁 1015-1018, 2010 IEEE International Ultrasonics Symposium, IUS 2010, San Diego, CA, 美國, 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 等.
2010 IEEE International Ultrasonics Symposium, IUS 2010. 2010. p. 1015-1018 5935814 (Proceedings - IEEE Ultrasonics Symposium).

研究成果: 圖書/報告稿件的類型 › 會議稿件 › 同行評審

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

摘要

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Conference

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指紋

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