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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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-07-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/optimization-of-molecularly-targeted-mri-in-the-brain-empirical-compar-peer-reviewed-article-IJN |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-18T02:27:19Z |
| format | Article |
| id | doaj.art-8b1d645da239466e9d3021362c44007a |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-18T02:27:19Z |
| publishDate | 2018-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-8b1d645da239466e9d3021362c44007a2022-12-21T21:24:00ZengDove Medical PressInternational Journal of Nanomedicine1178-20132018-07-01Volume 134345435939511Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particlesZarghami NKhrapitchev AAPerez-Balderas FSarmiento Soto MLarkin JRBau LSibson NRNiloufar 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, bSSFPhttps://www.dovepress.com/optimization-of-molecularly-targeted-mri-in-the-brain-empirical-compar-peer-reviewed-article-IJNMolecular imagingPreclinical MRIVCAM-MPIOVCAM-USPIOMulti gradient echobSSFP |
| spellingShingle | 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 International Journal of Nanomedicine Molecular imaging Preclinical MRI VCAM-MPIO VCAM-USPIO Multi gradient echo bSSFP |
| title | 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_short | 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 |
| topic | Molecular imaging Preclinical MRI VCAM-MPIO VCAM-USPIO Multi gradient echo bSSFP |
| url | https://www.dovepress.com/optimization-of-molecularly-targeted-mri-in-the-brain-empirical-compar-peer-reviewed-article-IJN |
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