Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles

Niloufar Zarghami,1 Alexandre A Khrapitchev,1 Francisco Perez-Balderas,1 Manuel Sarmiento Soto,1 James R Larkin,1 Luca Bau,2 Nicola R Sibson1 1Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK; 2Institut...

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Autores principales:	Zarghami N, Khrapitchev AA, Perez-Balderas F, Sarmiento Soto M, Larkin JR, Bau L, Sibson NR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Molecular imaging Preclinical MRI VCAM-MPIO VCAM-USPIO Multi gradient echo bSSFP Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8b1d645da239466e9d3021362c44007a
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spelling	oai:doaj.org-article:8b1d645da239466e9d3021362c44007a2021-12-02T04:14:08ZOptimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles1178-2013https://doaj.org/article/8b1d645da239466e9d3021362c44007a2018-07-01T00:00:00Zhttps://www.dovepress.com/optimization-of-molecularly-targeted-mri-in-the-brain-empirical-compar-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Niloufar Zarghami,1 Alexandre A Khrapitchev,1 Francisco Perez-Balderas,1 Manuel Sarmiento Soto,1 James R Larkin,1 Luca Bau,2 Nicola R Sibson1 1Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK; 2Institute of Biomedical Engineering, Department of Engineering Sciences, University of Oxford, Oxford, UK Background: Molecular MRI is an evolving field of research with strong translational potential. Selection of the appropriate MRI sequence, field strength and contrast agent depend largely on the application. The primary aims of the current study were to: 1) assess the sensitivity of different MRI sequences for detection of iron oxide particles in mouse brain; 2) determine the effect of magnetic field strength on detection of iron oxide particles in vivo; and 3) compare the sensitivity of targeted microparticles of iron oxide (MPIO) or ultra-small superparamagnetic iron oxide (USPIO) for detection of vascular cell adhesion molecule-1 (VCAM-1) in vivo. Methods: Mice were injected intrastriatally with interleukin 1β to induce VCAM-1 expression on the cerebral vasculature. Subsequently, animals were injected intravenously with either VCAM-MPIO or VCAM-USPIO and imaged 1 or 13 hours post-injection, respectively. MRI was performed at 4.7, 7.0, or 9.4 T, using three different T2*-weighted sequences: single gradient echo 3D (GE3D), multi-gradient echo 3D (MGE3D) and balanced steady-state free precession 3D (bSSFP3D). Results: MGE3D yielded the highest signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the detection of iron oxide particles. All sequences showed a significant increase in SNR and CNR from 4.7 to 7.0 T, but no further improvement at 9.4 T. However, whilst targeted MPIO enabled sensitive detection of VCAM-1 expression on the cerebral vasculature, the long half-life (16.5 h vs 1.2 min) and lower relaxivity per particle (1.29×10–14 vs 1.18×10–9 Hz L/particle) of USPIO vs. MPIO rendered them impractical for molecular MRI. Conclusion: These findings demonstrate clear advantages of MPIO compared to USPIO for molecularly-targeted MRI, and indicate that the MGE3D sequence is optimal for MPIO detection. Moreover, higher field strengths (7.0/9.4 T) showed enhanced sensitivity over lower field strengths (4.7 T). With the development of biodegradable MPIO, these agents hold promise for clinical translation. Keywords: molecular imaging, preclinical MRI, VCAM-MPIO, VCAM-USPIO, multi gradient echo, bSSFPZarghami NKhrapitchev AAPerez-Balderas FSarmiento Soto MLarkin JRBau LSibson NRDove Medical PressarticleMolecular imagingPreclinical MRIVCAM-MPIOVCAM-USPIOMulti gradient echobSSFPMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4345-4359 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular imaging Preclinical MRI VCAM-MPIO VCAM-USPIO Multi gradient echo bSSFP Medicine (General) R5-920
spellingShingle	Molecular imaging Preclinical MRI VCAM-MPIO VCAM-USPIO Multi gradient echo bSSFP Medicine (General) R5-920 Zarghami N Khrapitchev AA Perez-Balderas F Sarmiento Soto M Larkin JR Bau L Sibson NR Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles
description	Niloufar Zarghami,1 Alexandre A Khrapitchev,1 Francisco Perez-Balderas,1 Manuel Sarmiento Soto,1 James R Larkin,1 Luca Bau,2 Nicola R Sibson1 1Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK; 2Institute of Biomedical Engineering, Department of Engineering Sciences, University of Oxford, Oxford, UK Background: Molecular MRI is an evolving field of research with strong translational potential. Selection of the appropriate MRI sequence, field strength and contrast agent depend largely on the application. The primary aims of the current study were to: 1) assess the sensitivity of different MRI sequences for detection of iron oxide particles in mouse brain; 2) determine the effect of magnetic field strength on detection of iron oxide particles in vivo; and 3) compare the sensitivity of targeted microparticles of iron oxide (MPIO) or ultra-small superparamagnetic iron oxide (USPIO) for detection of vascular cell adhesion molecule-1 (VCAM-1) in vivo. Methods: Mice were injected intrastriatally with interleukin 1β to induce VCAM-1 expression on the cerebral vasculature. Subsequently, animals were injected intravenously with either VCAM-MPIO or VCAM-USPIO and imaged 1 or 13 hours post-injection, respectively. MRI was performed at 4.7, 7.0, or 9.4 T, using three different T2*-weighted sequences: single gradient echo 3D (GE3D), multi-gradient echo 3D (MGE3D) and balanced steady-state free precession 3D (bSSFP3D). Results: MGE3D yielded the highest signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the detection of iron oxide particles. All sequences showed a significant increase in SNR and CNR from 4.7 to 7.0 T, but no further improvement at 9.4 T. However, whilst targeted MPIO enabled sensitive detection of VCAM-1 expression on the cerebral vasculature, the long half-life (16.5 h vs 1.2 min) and lower relaxivity per particle (1.29×10–14 vs 1.18×10–9 Hz L/particle) of USPIO vs. MPIO rendered them impractical for molecular MRI. Conclusion: These findings demonstrate clear advantages of MPIO compared to USPIO for molecularly-targeted MRI, and indicate that the MGE3D sequence is optimal for MPIO detection. Moreover, higher field strengths (7.0/9.4 T) showed enhanced sensitivity over lower field strengths (4.7 T). With the development of biodegradable MPIO, these agents hold promise for clinical translation. Keywords: molecular imaging, preclinical MRI, VCAM-MPIO, VCAM-USPIO, multi gradient echo, bSSFP
format	article
author	Zarghami N Khrapitchev AA Perez-Balderas F Sarmiento Soto M Larkin JR Bau L Sibson NR
author_facet	Zarghami N Khrapitchev AA Perez-Balderas F Sarmiento Soto M Larkin JR Bau L Sibson NR
author_sort	Zarghami N
title	Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles
title_short	Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles
title_full	Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles
title_fullStr	Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles
title_full_unstemmed	Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles
title_sort	optimization of molecularly targeted mri in the brain: empirical comparison of sequences and particles
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/8b1d645da239466e9d3021362c44007a
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Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles

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