QUTE-CE MRI is a breakthrough in Quantitative MRI.
Related Publications
Timms, Liam; Zhou, Tianyi; Lyu, Yue; Qiao, Ju; Mishra, Vishala; Lahoud, Rita Maria; Jayaraman, Gayatri Veeramani; Allegretti, Andrew S; Drew, David; Seethamraju, Ravi T; others, Ferumoxytol-enhanced ultrashort TE MRA and quantitative morphometry of the human kidney vasculature Journal Article In: Abdominal Radiology, vol. 46, pp. 3288–3300, 2021. Tags: MRI Qiao, Ju; Cai, Xuezhu; Xiao, Qian; Chen, Zhengxi; Kulkarni, Praveen; Ferris, Craig; Kamarthi, Sagar; Sridhar, Srinivas Data on MRI brain lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization Journal Article In: Data in brief, vol. 27, pp. 104628, 2019. Thanh, Nguyen; Phuc, Xuan; Sridhar, Srinivas Nanoscale Magnetism in Next Generation Magnetic Nanoparticles Technical Report UNIVERSITY COLLEGE LONDON London United Kingdom 2018. Abstract | Tags: MRI, Nanomedicine Codi, Gharagouzloo; Qiao, Ju; Timms, Liam; van de Ven, Anne; Sridhar, Srinivas Abstract B22: Quantitative tumor imaging using magnetic nanoparticles Miscellaneous 2017. Gharagouzloo, Codi A; Timms, Liam; Qiao, Ju; Fang, Zihang; Nneji, Joseph; Pandya, Aniket; Kulkarni, Praveen; van de Ven, Anne L; Ferris, Craig; Sridhar, Srinivas Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function Journal Article In: Neuroimage, vol. 163, pp. 24–33, 2017. Gharagouzloo, Codi; Sridhar, Srinivas Quantitative magnetic resonance imaging of the vasculature Miscellaneous 2017. Wang, Haotian; Kumar, Rajiv; Nagesha, Dattatri; Jr, Richard I Duclos; Sridhar, Srinivas; Gatley, Samuel J Integrity of 111In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse Journal Article In: Nuclear medicine and biology, vol. 42, no. 1, pp. 65–70, 2015. Abstract | Tags: MRI, Nanomedicine Gharagouzloo, Codi Amir; McMahon, Patrick N; Sridhar, Srinivas Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences Journal Article In: Magnetic resonance in medicine, vol. 74, no. 2, pp. 431–441, 2015. Tags: MRI, Nanomedicine Sridhar, S; Kumar, Rajesh P; Ramanaiah, KV Wavelet Transform Techniques for Image Compression-An Evaluation Journal Article In: International journal of image, graphics and signal processing, vol. 6, no. 2, pp. 54, 2014. Gharagouzloo, CA; Madi, S; Seethamraju, RT; Harisinghani, M; Sridhar, S Ultrashort TE imaging with SPIONs: bright prospects for in vivo applications Proceedings Article In: JOURNAL OF NUCLEAR MEDICINE, pp. 9–9, SOC NUCLEAR MEDICINE INC 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA 2013. Tags: MRI Gharagouzloo, Codi; Jillela, Manasa; Kumar, Rajiv; Nagesha, Dattatri; Sridhar, Srinivas Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery. Miscellaneous 2013. Sridhar, Srinivas; Campbell, Robert; Nagesha, Dattatri; Gultepe, Evin Magnetic nanoplatforms for tumor targeting, imaging and energy delivery Miscellaneous 2011. Sawant, RM; Nagesha, D; Sridhar, S; Torchilin, VP Polymeric Magnetomicelles As a Probe for MRI Imaging: Characterization and Mri Properties Journal Article In: 0000. Gharagouzloo, Codi Amir; Ma, Chao; Verwer, Eline E; Mandeville, Joseph B; Huang, Chuan; Sridhar, Srinivas; Fakhri, Georges El; Wooten, Dustin W; Normandin, Marc D Functional neuroimaging using dynamic radial 3D UTE pulse sequences Journal Article In: 0000. Sawant, RM; Gultepe, E; Nagesha, D; Sridhar, S; Torchilin, VP Developing superparamagnetic iron oxide nanoparticles as tumor-specific magnetic resonance imaging (MRI) contrast agents Journal Article In: 0000.@article{timms2021ferumoxytol,
title = {Ferumoxytol-enhanced ultrashort TE MRA and quantitative morphometry of the human kidney vasculature},
author = {Liam Timms and Tianyi Zhou and Yue Lyu and Ju Qiao and Vishala Mishra and Rita Maria Lahoud and Gayatri Veeramani Jayaraman and Andrew S Allegretti and David Drew and Ravi T Seethamraju and others},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Abdominal Radiology},
volume = {46},
pages = {3288–3300},
publisher = {Springer US},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
@article{qiao2019data,
title = {Data on MRI brain lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization},
author = {Ju Qiao and Xuezhu Cai and Qian Xiao and Zhengxi Chen and Praveen Kulkarni and Craig Ferris and Sagar Kamarthi and Srinivas Sridhar},
year = {2019},
date = {2019-01-01},
journal = {Data in brief},
volume = {27},
pages = {104628},
publisher = {Elsevier},
abstract = {The data in this article provide details about MRI lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization (GMM-EM) algorithms. Both K-means and GMM-EM algorithms can segment lesion area from the rest of brain MRI automatically. The performance metrics (accuracy, sensitivity, specificity, false positive rate, misclassification rate) were estimated for the algorithms and there was no significant difference between K-means and GMM-EM. In addition, lesion size does not affect the accuracy and sensitivity for either method.},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
@techreport{thanh2018nanoscale,
title = {Nanoscale Magnetism in Next Generation Magnetic Nanoparticles},
author = {Nguyen Thanh and Xuan Phuc and Srinivas Sridhar},
year = {2018},
date = {2018-01-01},
institution = {UNIVERSITY COLLEGE LONDON London United Kingdom},
abstract = {Short summary of most important research results that explain why the work was done, what was accomplished, and how it pushed scientific frontiers or advanced the field. This summary will be used for archival purposes and will be added to a searchable DoD database. Magnetic nanoparticles (MNPs) are key components of a variety of sensors for diverse applications in electronics and biotechnologies. Nanoparticle properties are critically affected both by nanoscale size as well as surface interactions with the environment. These interactions among the key fundamental properties such as magnetic moment and dynamic response that are required for use in applications. In this we have had a collaborative project between groups at Northeastern University (USA), University College London-UCL (UK) and Institute of Materials Science (Vietnam Academy of Science and Technology-VAST) to synthesis and understand the fundamental aspects of magnetism at the nanometer length scale in confined geometries in nanoparticles. At Northeastern University, we studied the dynamic relaxation of superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous media. Using the MRI facilities at Northeastern University, MNPs from collaborators UCL and VAST as well as dextran coated SPIONs were studied. From the measured T1 and T2 relaxation times, a new method called Quantitative Ultra-Short Time-to-Echo Contrast Enhanced (QUTE-CE) Magnetic Resonance Imaging (MRI) was developed. The method was tested in vivo and demonstrated to yield positive contrast angiograms with high clarity and definition, and enabled quantitative MRI in biological samples. At UCL, the work included (i) fabricating multi-element magnetic systems, and (ii) controlling interactions by surface modification using organic compounds. The project involves systematic matter property studies by fabrication of novel organically modified coating of MNPs, physical characterization at both macroscopic level such as magnetic moments and AC susceptibility as well as microscopic one. The results provided fundamental insights into the nature of nanoscale magnetism relevant to a variety of nanomagnetic applications.At Institute of Materials Science, Vietnam Academy of Science and Technology, apart from the effort to synthesize MNPs of high magnetization and monodispersity, we have also studied in details various parameters which may impact on magnetic heating power of MNPs of different materials, such as particle size, size distribution, ferrofluid viscosity etc. The 3-year collaborative project has resulted in 9 publications in peer-reviewed journals and 34 presentations in major conferences, meeting and workshops around the world.
},
keywords = {MRI, Nanomedicine},
pubstate = {published},
tppubtype = {techreport}
}
@misc{codi2017abstract,
title = {Abstract B22: Quantitative tumor imaging using magnetic nanoparticles},
author = {Gharagouzloo Codi and Ju Qiao and Liam Timms and Anne van de Ven and Srinivas Sridhar},
year = {2017},
date = {2017-01-01},
publisher = {American Association for Cancer Research},
abstract = {Introduction: We have developed a new method of Quantitative MRI named QUTE-CE MRI that yields images of the vasculature with unparalleled clarity and definition and is quantitative. QUTE-CE MRI can produce contrast enhanced magnetic resonance angiograms (CE-MRA) using super paramagnetic iron-oxide nanoparticle (SPION), including the FDA approved ferumoxytol, with high contrast in cardiovascular, cerebral, and tumor imaging.
Based upon principles of magnetic nanoparticle interactions with neighboring water molecules, the method achieves robust, reproducible results by utilizing rapid signal acquisition at ultra-short time-to-echo (UTE) to produce positive-contrast images with pure T1 weighting and little T2* decay. The spoiled gradient echo equation (SPGR) is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters.
Methods: All animal experiments were conducted in accordance with the Northeastern University Division of Laboratory Animal Medicine and Institutional Animal Care and Use Committee. MRI images were obtained at ambient temperature (∼25°C) using a Bruker Biospec 7.0T/20-cm USR horizontal magnet (Bruker, Billerica, Massachusetts, USA) equipped with a 20-G/cm magnetic field gradient insert (ID =12 cm, Bruker) and the same quadrature 300 MHz, 30 mm Mouse MRI coil was used for all in vivo work as previously utilized for mouse experiments in Section 3.8 (Animal Imaging Research, LLC, Holden, Massachusetts, USA).
PC 3 cells were injected into the right flank of immunocompromised FoxNu1 mice (n=5, Charles River Laboratories). After tumors reached about 0.5-1.0cm3, animals underwent three separate imaging sessions: Session 1 - pre-contrast T1, T2 and QUTE-CE measurements, Session 2 - immediate post-contrast QUTE-CE measurement and Session 3 - 24h post-contrast T1, T2 and QUTE-CE measurements. For contrast, 100μl of ferumoxytol diluted to 6mg/ml was injected i.v. to render a blood concentration of ~200μg/ml Fe (2x clinical dose).
Results: Contrary to more standard MRI techniques, QUTE-CE pre-contrast images render a nearly homogenous signal with a Gaussian distribution in the tumor. The immediate post-contrast images render the vasculature clearly and skew the distribution of voxels within the whole tumor to the left, however also increases the overall mean of the signal intensity because the movement of voxels within the tumor is to the right, leaving a long bright tail with the brightest voxels represented by those containing 100% blood. 24h after the initial administration of ferumoxytol the vasculature is no longer visible, but the locations within the tumor that have passively accumulated SPIONs resulting from the EPR effect becomes apparent. While the distribution of voxels within the tumor becomes less skewed, the overall shape is still slightly skewed to the left and the mean of the distribution has moved to the right. Nanoparticle accumulation in the post-contrast image is heterogeneous and unambiguous.
Angiography and TBV in tumors Assuming a partial 2-volume model of blood and tissue, we determine the tumor blood volume (TBV) across the entire tumor volume. The resultant TBV heatmaps show a clear range of TBV values are apparent, delineating areas of the tissue with high contrast in regard to overall vascular health, including apparently necrotic tissue.
Nanoparticle accumulation Next, a unique feature of the methodology to produce high-contrast images of purely T1-weighted signal is employed to unambiguously delineate nanoparticle accumulation in a PC3 subcutaneous tumor model with ferumoxytol accumulation 24 hours after just one dose. From this, contrast efficiency was produced compared to standard techniques with the additional benefit that pre-contrast images are not necessitated. A major advantage of delineating SPION accumulation using QUTE-CE, compared to ΔT2 or ΔT1 imaging, is that the post-contrast image contains sufficient information for nanoparticle localization, eliminating the need for pre-contrast images.
Conclusion: QUTE-CE MRI exploits physical principles of magnetic relaxation modulated by SPIONs to achieve quantitative MRI yielding exceptional vascular images. This ability to longitudinally quantify blood pool CA concentration is unique to the QUTE-CE method, and makes QUTE-CE MRI competitive with nuclear imaging. Quantitative tumor blood volume distributions are obtained at short times, while nanoparticle accumulation maps are obtained at long times. QUTE-CE MRI is a new method that can be used to study tumor properties longitudinally. The technique is immediately translatable to the clinic using the FDA approved contrast agent ferumoxytol and is expected to have a major impact on clinical tumor imaging.
Work supported by NSF-DGE- 0965843.
Citation Format: Gharagouzloo Codi, Ju Qiao, Liam Timms, Anne van de Ven, Srinivas Sridhar. Quantitative tumor imaging using magnetic nanoparticles. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B22.
©2016 American Association for Cancer Research.},
keywords = {MRI},
pubstate = {published},
tppubtype = {misc}
}
Based upon principles of magnetic nanoparticle interactions with neighboring water molecules, the method achieves robust, reproducible results by utilizing rapid signal acquisition at ultra-short time-to-echo (UTE) to produce positive-contrast images with pure T1 weighting and little T2* decay. The spoiled gradient echo equation (SPGR) is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters.
Methods: All animal experiments were conducted in accordance with the Northeastern University Division of Laboratory Animal Medicine and Institutional Animal Care and Use Committee. MRI images were obtained at ambient temperature (∼25°C) using a Bruker Biospec 7.0T/20-cm USR horizontal magnet (Bruker, Billerica, Massachusetts, USA) equipped with a 20-G/cm magnetic field gradient insert (ID =12 cm, Bruker) and the same quadrature 300 MHz, 30 mm Mouse MRI coil was used for all in vivo work as previously utilized for mouse experiments in Section 3.8 (Animal Imaging Research, LLC, Holden, Massachusetts, USA).
PC 3 cells were injected into the right flank of immunocompromised FoxNu1 mice (n=5, Charles River Laboratories). After tumors reached about 0.5-1.0cm3, animals underwent three separate imaging sessions: Session 1 - pre-contrast T1, T2 and QUTE-CE measurements, Session 2 - immediate post-contrast QUTE-CE measurement and Session 3 - 24h post-contrast T1, T2 and QUTE-CE measurements. For contrast, 100μl of ferumoxytol diluted to 6mg/ml was injected i.v. to render a blood concentration of ~200μg/ml Fe (2x clinical dose).
Results: Contrary to more standard MRI techniques, QUTE-CE pre-contrast images render a nearly homogenous signal with a Gaussian distribution in the tumor. The immediate post-contrast images render the vasculature clearly and skew the distribution of voxels within the whole tumor to the left, however also increases the overall mean of the signal intensity because the movement of voxels within the tumor is to the right, leaving a long bright tail with the brightest voxels represented by those containing 100% blood. 24h after the initial administration of ferumoxytol the vasculature is no longer visible, but the locations within the tumor that have passively accumulated SPIONs resulting from the EPR effect becomes apparent. While the distribution of voxels within the tumor becomes less skewed, the overall shape is still slightly skewed to the left and the mean of the distribution has moved to the right. Nanoparticle accumulation in the post-contrast image is heterogeneous and unambiguous.
Angiography and TBV in tumors Assuming a partial 2-volume model of blood and tissue, we determine the tumor blood volume (TBV) across the entire tumor volume. The resultant TBV heatmaps show a clear range of TBV values are apparent, delineating areas of the tissue with high contrast in regard to overall vascular health, including apparently necrotic tissue.
Nanoparticle accumulation Next, a unique feature of the methodology to produce high-contrast images of purely T1-weighted signal is employed to unambiguously delineate nanoparticle accumulation in a PC3 subcutaneous tumor model with ferumoxytol accumulation 24 hours after just one dose. From this, contrast efficiency was produced compared to standard techniques with the additional benefit that pre-contrast images are not necessitated. A major advantage of delineating SPION accumulation using QUTE-CE, compared to ΔT2 or ΔT1 imaging, is that the post-contrast image contains sufficient information for nanoparticle localization, eliminating the need for pre-contrast images.
Conclusion: QUTE-CE MRI exploits physical principles of magnetic relaxation modulated by SPIONs to achieve quantitative MRI yielding exceptional vascular images. This ability to longitudinally quantify blood pool CA concentration is unique to the QUTE-CE method, and makes QUTE-CE MRI competitive with nuclear imaging. Quantitative tumor blood volume distributions are obtained at short times, while nanoparticle accumulation maps are obtained at long times. QUTE-CE MRI is a new method that can be used to study tumor properties longitudinally. The technique is immediately translatable to the clinic using the FDA approved contrast agent ferumoxytol and is expected to have a major impact on clinical tumor imaging.
Work supported by NSF-DGE- 0965843.
Citation Format: Gharagouzloo Codi, Ju Qiao, Liam Timms, Anne van de Ven, Srinivas Sridhar. Quantitative tumor imaging using magnetic nanoparticles. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B22.
©2016 American Association for Cancer Research.@article{gharagouzloo2017quantitative,
title = {Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function},
author = {Codi A Gharagouzloo and Liam Timms and Ju Qiao and Zihang Fang and Joseph Nneji and Aniket Pandya and Praveen Kulkarni and Anne L van de Ven and Craig Ferris and Srinivas Sridhar},
year = {2017},
date = {2017-01-01},
journal = {Neuroimage},
volume = {163},
pages = {24--33},
publisher = {Academic Press},
abstract = {A method called Quantitative Ultra-Short Time-to-Echo Contrast Enhanced (QUTE-CE) Magnetic Resonance Imaging (MRI) which utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent to yield positive contrast angiograms with high clarity and definition is applied to the whole live rat brain. QUTE-CE MRI intensity data are particularly well suited for measuring quantitative cerebral blood volume (qCBV). A global map of qCBV in the awake resting-state with unprecedented detail was created via application of a 3D MRI rat brain atlas with 173 segmented and annotated brain areas. From this map we identified two distributed, integrated neural circuits showing the highest capillary densities in the brain. One is the neural circuitry involved with the primary senses of smell, hearing and vision and the other is the neural circuitry of memory. Under isoflurane anesthesia, these same circuits showed significant decreases in qCBV suggesting a role in consciousness. Neural circuits in the brainstem associated with the reticular activating system and the maintenance of respiration, body temperature and cardiovascular function showed an increase in qCBV with anesthesia. During awake CO2 challenge, 84 regions showed significant increases relative to an awake baseline state. This CO2 response provides a measure of cerebral vascular reactivity and regional perfusion reserve with the highest response measured in the somatosensory cortex. These results demonstrate the utility of QUTE-CE MRI for qCBV analysis and offer a new perspective on brain function and vascular organization.},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
@misc{gharagouzloo2017quantitativeb,
title = {Quantitative magnetic resonance imaging of the vasculature},
author = {Codi Gharagouzloo and Srinivas Sridhar},
year = {2017},
date = {2017-01-01},
abstract = {A quantitative, ultrashort time to echo, contrast-enhanced magnetic resonance imaging technique is provided. The technique can be used to accurately measure contrast agent concentration in the blood, to provide clear, high-definition angiograms, and to measure absolute quantities of cerebral blood volume on a voxel -by- voxel basis.},
keywords = {MRI},
pubstate = {published},
tppubtype = {misc}
}
@article{wang2015integrity,
title = {Integrity of 111In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse},
author = {Haotian Wang and Rajiv Kumar and Dattatri Nagesha and Richard I Duclos Jr and Srinivas Sridhar and Samuel J Gatley},
year = {2015},
date = {2015-01-01},
journal = {Nuclear medicine and biology},
volume = {42},
number = {1},
pages = {65--70},
publisher = {Elsevier},
abstract = {Introduction
Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo.
Methods
We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with 59Fe, 14C-oleic acid, and 111In.
Results
Mouse biodistributions showed 111In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59Fe than 111In in liver and spleen, but lower levels of 14C.
Conclusions
While there is some degree of dissociation between the 111In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component.},
keywords = {MRI, Nanomedicine},
pubstate = {published},
tppubtype = {article}
}
Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo.
Methods
We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with 59Fe, 14C-oleic acid, and 111In.
Results
Mouse biodistributions showed 111In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59Fe than 111In in liver and spleen, but lower levels of 14C.
Conclusions
While there is some degree of dissociation between the 111In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component.@article{gharagouzloo2015quantitative,
title = {Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences},
author = {Codi Amir Gharagouzloo and Patrick N McMahon and Srinivas Sridhar},
year = {2015},
date = {2015-01-01},
journal = {Magnetic resonance in medicine},
volume = {74},
number = {2},
pages = {431--441},
keywords = {MRI, Nanomedicine},
pubstate = {published},
tppubtype = {article}
}
@article{sridhar2014wavelet,
title = {Wavelet Transform Techniques for Image Compression-An Evaluation},
author = {S Sridhar and Rajesh P Kumar and KV Ramanaiah},
year = {2014},
date = {2014-01-01},
journal = {International journal of image, graphics and signal processing},
volume = {6},
number = {2},
pages = {54},
publisher = {Modern Education and Computer Science Press},
abstract = {A vital problem in evaluating the picture quality of an image compression system is the difficulty in describing the amount of degradation in reconstructed image, Wavelet transforms are set of mathematical functions that have established their viability in image compression applications owing to the computational simplicity that comes in the form of filter bank implementation. The choice of wavelet family depends on the application and the content of image. Proposed work is carried out by the application of different hand designed wavelet families like Haar, Daubechies, Biorthogonal, Coiflets and Symlets etc on a variety of bench mark images. Selected benchmark images of choice are decomposed twice using appropriate family of wavelets to produce the approximation and detail coefficients. The highly accurate approximation coefficients so produced are further quantized and later Huffman encoded to eliminate the psychovisual and coding redundancies. However the less accurate detailed coefficients are neglected. In this paper the relative merits of different Wavelet transform techniques are evaluated using objective fidelity measures- PSNR and MSE, results obtained provide a basis for application developers to choose the right family of wavelet for image compression matching their application.},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
@inproceedings{gharagouzloo2013ultrashort,
title = {Ultrashort TE imaging with SPIONs: bright prospects for in vivo applications},
author = {CA Gharagouzloo and S Madi and RT Seethamraju and M Harisinghani and S Sridhar},
year = {2013},
date = {2013-01-01},
booktitle = {JOURNAL OF NUCLEAR MEDICINE},
volume = {54},
pages = {9--9},
organization = {SOC NUCLEAR MEDICINE INC 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA},
keywords = {MRI},
pubstate = {published},
tppubtype = {inproceedings}
}
@misc{gharagouzloo2013positive,
title = {Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery.},
author = {Codi Gharagouzloo and Manasa Jillela and Rajiv Kumar and Dattatri Nagesha and Srinivas Sridhar},
year = {2013},
date = {2013-01-01},
publisher = {American Association for Cancer Research},
abstract = {During the last 2 decades no new clinical MRI agents have been approved for clinical use. While Gadolinium based agents have been very popular, Gd cannot be used in emerging multi-functional nano platforms that have the potential to be retained in the body leading to severe toxicity. Superparamagnetic iron-oxide nanoparticles (SPIONs) are most attractive as offering a significant alternative that is far less toxic than Gd based agents. They can be incorporated into nanoplatforms combining other therapeutic agents to achieve image guided drug delivery. Conventionally, SPIONs are imaged via T2 and T2* weighted techniques which manifest signal voids for SPION-containing media. This proves to be disadvantageous in most circumstances because of the difficulty in discriminating signal loss from tissue associated partial voluming, perivascular effects, susceptibility artifacts and motion or flow artifacts. The unique combination of SPIONs with ultra-short TE (UTE) imaging has the specific advantages of rendering positive contrast with high SNR and high CNR, since non-SPION containing regions are dramatically dark due to native tissue's comparatively higher T1. With UTE, it may be possible to take advantage of SPION's inherent biocompatibility allowing for incorporation into drug loaded nanoplatforms leading to bright contrast and the possibility of in vivo quantification.
Here, we report on a systematic study of positive contrast MR imaging using magnetic nanoplatforms incorporating SPIONs of varying particle size and functionalization. In the first step, nanoparticles of various sizes from 4 nm to 20 nm were synthesized by the thermal decomposition method in organic solvents and then coated with phospholipids containing PEG. The use of PEGylated phospholipid enables water solubility, imparts better dispersity and long circulation in blood stream. This results in a core-shell like morphology with iron oxide nanoparticle forming the core and phospholipid PEG forming the shell. The nanoparticles were characterized for their size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM). UTE was optimized on a Bruker 7T Biospec at the Center for Translational Neuroimaging (CTNI) at Northeastern University. High-contrast images were obtained by modification of various imaging parameters such as TE, TR, flip angle, pulse length, polar under-sampling, bandwidth and FOV/Geometry. The results are compared in vivo with Feraheme and show good promise for this approach to MR nanoparticle imaging.
We acknowledge partial support from NSF DGE 0965843, HHS/5U54CA151881-02, and the Electronics Materials Research Institute at Northeastern University.
Citation Format: Codi Gharagouzloo, Manasa Jillela, Rajiv Kumar, Dattatri Nagesha, Srinivas Sridhar. Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2673. doi:10.1158/1538-7445.AM2013-2673
©2013 American Association for Cancer Research},
keywords = {MRI},
pubstate = {published},
tppubtype = {misc}
}
Here, we report on a systematic study of positive contrast MR imaging using magnetic nanoplatforms incorporating SPIONs of varying particle size and functionalization. In the first step, nanoparticles of various sizes from 4 nm to 20 nm were synthesized by the thermal decomposition method in organic solvents and then coated with phospholipids containing PEG. The use of PEGylated phospholipid enables water solubility, imparts better dispersity and long circulation in blood stream. This results in a core-shell like morphology with iron oxide nanoparticle forming the core and phospholipid PEG forming the shell. The nanoparticles were characterized for their size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM). UTE was optimized on a Bruker 7T Biospec at the Center for Translational Neuroimaging (CTNI) at Northeastern University. High-contrast images were obtained by modification of various imaging parameters such as TE, TR, flip angle, pulse length, polar under-sampling, bandwidth and FOV/Geometry. The results are compared in vivo with Feraheme and show good promise for this approach to MR nanoparticle imaging.
We acknowledge partial support from NSF DGE 0965843, HHS/5U54CA151881-02, and the Electronics Materials Research Institute at Northeastern University.
Citation Format: Codi Gharagouzloo, Manasa Jillela, Rajiv Kumar, Dattatri Nagesha, Srinivas Sridhar. Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2673. doi:10.1158/1538-7445.AM2013-2673
©2013 American Association for Cancer Research@misc{sridhar2011magnetic,
title = {Magnetic nanoplatforms for tumor targeting, imaging and energy delivery},
author = {Srinivas Sridhar and Robert Campbell and Dattatri Nagesha and Evin Gultepe},
year = {2011},
date = {2011-01-01},
publisher = {American Association for Cancer Research},
abstract = {We have developed magnetic nano-liposomes (MNL), incorporating superparamagnetic iron oxide nanoparticles (SPION), that are versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MNL are prepared with a formuation of DPPC:DOTAP:CHOL and DOPE-PEG5000. Incorporation of SPIONs results in MNL with mean diameter of 150-250 nm. MNL are easily taken up by B16-F10 melanoma, HUMVEC-D and breast cancer cell lines. They preferentially target the tumor vasculature as shown in a dorsal skin fold chamber using fluorescently labeled MNL. MNL display superparamagnetic response that is essential for magnetic targeting, MR contrast enhancement and magnetic heating.
MNL was administrated to SCID mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In labeled MNL and amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations.
We have shown that tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2-fold greater accumulation by magnetic targeting.
111In radio-labeled MNL have been shown to enable multi-modal imaging in vivo using MRI and SPeCT/CT. The images show that an MNL bolus injected intra-tumorally was retained in the tumor 24 hours after injection. Application of a magnetic field enables redistribution of the MNL in the tumor.
These MNL are also responsive to ac magnetic fields applied using a Copper coil at 360 kHz and 170A driving current. Both hyperthermia (upto 45C) and thermo-ablative temperatures upto 90C were achieved in 10 – 30 minutes ex vivo in buffer. The results indicate high efficiency for magnetic heating using MNL (Specific Absorption Rate ∼ 104 W/kg) and demonstrate the capability to couple ac magnetic fields to MNL to achieve any set of temperatures needed for hyperthermia and thermal ablation.
To date there are no truly theranostic platforms that have been approved for clinical use that combine targeting, thermal heating and MRI imaging capabilities. Existing FDA approved magnetic nanoparticle formulations like ferridex and ferumoxytol, are optimized for MR imaging, and have not been shown to be usable for thermal therapy.The MNL platform is a novel nanoplatform combining multi-modal imaging capabilities, with magnetic targeting and thermal therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2011-380
©2011 American Association for Cancer Research},
keywords = {MRI},
pubstate = {published},
tppubtype = {misc}
}
MNL was administrated to SCID mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In labeled MNL and amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations.
We have shown that tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2-fold greater accumulation by magnetic targeting.
111In radio-labeled MNL have been shown to enable multi-modal imaging in vivo using MRI and SPeCT/CT. The images show that an MNL bolus injected intra-tumorally was retained in the tumor 24 hours after injection. Application of a magnetic field enables redistribution of the MNL in the tumor.
These MNL are also responsive to ac magnetic fields applied using a Copper coil at 360 kHz and 170A driving current. Both hyperthermia (upto 45C) and thermo-ablative temperatures upto 90C were achieved in 10 – 30 minutes ex vivo in buffer. The results indicate high efficiency for magnetic heating using MNL (Specific Absorption Rate ∼ 104 W/kg) and demonstrate the capability to couple ac magnetic fields to MNL to achieve any set of temperatures needed for hyperthermia and thermal ablation.
To date there are no truly theranostic platforms that have been approved for clinical use that combine targeting, thermal heating and MRI imaging capabilities. Existing FDA approved magnetic nanoparticle formulations like ferridex and ferumoxytol, are optimized for MR imaging, and have not been shown to be usable for thermal therapy.The MNL platform is a novel nanoplatform combining multi-modal imaging capabilities, with magnetic targeting and thermal therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2011-380
©2011 American Association for Cancer Research@article{sawantpolymeric,
title = {Polymeric Magnetomicelles As a Probe for MRI Imaging: Characterization and Mri Properties},
author = {RM Sawant and D Nagesha and S Sridhar and VP Torchilin},
abstract = {Superparamagnetic iron oxide nanoparticles (SPIONs) coated with silane were prepared and entrapped in polymeric micelles made from PEG-PE using hepes-buffered saline pH 7.4. The SPIONs entrapped in these micelles had excellent stability and did tend to aggregate at the conditions store. In contrast “plain” SPIONs collapsed from solution and did not show any ability to remain dispersed. SPION-micelles thus prepared have shown an improved relaxivity at low concentration of entrapped SPIONs, which makes them to be promising contrast agents for T2 MRI imaging.},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
@article{gharagouzloofunctional,
title = {Functional neuroimaging using dynamic radial 3D UTE pulse sequences},
author = {Codi Amir Gharagouzloo and Chao Ma and Eline E Verwer and Joseph B Mandeville and Chuan Huang and Srinivas Sridhar and Georges El Fakhri and Dustin W Wooten and Marc D Normandin},
abstract = {Functional MR neuroimaging is an essential tool for studying brain activity. Cerebral blood volume (CBV) is an important indicator of brain function, but measurements are typically qualitative or relative. Furthermore, warping and signal drift necessitate significant image pre-processing with standard EPI acquisition. In this work, we utilize a radial 3D UTE pulse sequence with optimized acquisition parameters determined from phantoms and modeling. Feasibility of dynamic UTE as a functional neuroimaging method is demonstrated in non-human primates receiving NBOH-2C-CN, a 5-HT2A receptor agonist. CBV is measured dynamically throughout the whole brain and shown to agree well with an analogous EPI experiment.
PURPOSE
The three primary physiological indicators of neural activity in fMRI are changes in cerebral blood volume (CBV), blood flow and oxygenated state of hemoglobin.To isolate the CBV-induced signal change, T2*-weighted echo-planar imaging (EPI) sequences are commonly utilized with intravascular contrast agent to overshadow contrast from changes in blood oxygenation and enhance signal from CBV changes. While EPI sequences are fast, they are prone to significant distortion artifact. Additionally, macroscopic susceptibility artifacts confound the MR signal and are difficult to separate from baseline blood oxygenation level dependent (BOLD) effects; thus results are qualitative. Ultra-short time-to-echo (UTE) sequences are insensitive to susceptibility changes and extravoxular signal dephasing. Thus, we propose to use quantitative UTE contrast-enhanced (QUTE-CE) MRI to measure CBV changes dynamically.
METHODS
QUTE-CE MRI is the combination of acquisition with an optimized 3D UTE pulse sequence and an intra-vascular contrast agent1 to render a highly quantitative signal. Ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, Massachusetts, USA) was used for contrast.
Relaxation rates were measured in 1% heparinized whole-calf-blood (Fig. 1a,-c) and modeling with the spoiled gradient echo (SPGR) equation was used to determine optimized parameters for efficient dynamic scans (Fig. 1d). CBV is calculated by simple partial volume calculations. The effect of signal modification by vascular water molecule exchange is suppressed with low TR and high FA2. Modeling signal intensity with two compartments:
IM=fBIb+(1−fB)IT
where, IT is the brain tissue intensity, IB is the blood intensity and fB is the fraction of the voxel occupied by blood. For each image volume, CBV is calculated voxel-by-voxel by subtracting a pre-contrast image then scaling the results by the blood intensity as determined in a large vessel:
fB=CBV=I,M−IMI,B−IB
Animal experiments were conducted under an approved IACUC protocol. A dynamic QUTE-CE study was performed with ferumoxytol on a non-human primate (NHP) with NBOH-2C-CN, a potent and selective 5-HT2A receptor agonist, and results were compared to the current gold standard EPI + ferumoxytol imaging. All imaging was performed on a Siemens 3T Tim Trio magnet. NHPs were anesthetized throughout the scan with isoflurane (1-3%). EPI and UTE scans consisted of three imaging phases: pre-contrast followed by a bolus of 10mg/kg ferumoxytol post-contrast and then administration of 50 mcg/kg of NBOH-2C-CN. Single-shot EPI was accelerated in the phase-encode direction by a factor of two providing an isotropic spatial resolution of 1.3mm and TE=23ms.
RESULTS
QUTE-CE pre-contrast images rendered dark blood with a small amount of tissue contrast in NHPs (Fig. 2a). Bright positive contrast of the blood was achieved after injection of ferumoxytol (Fig. 2b-d). Vasculature was clearly visible and all parts of the anatomy were free of image warping (Fig 2a-c). In contrast, time-averaged EPI data equal to the duration of the dynamic UTE scan exhibited significant signal dropout in the anterior and posterior brain, with obvious image warping (Fig 2f). The same custom-built 8-channel receive coil was used in both acquisitions. Maps of absolute CBV obtained from pre- and post-contrast UTE images are of high quality and have quantitative values consistent with expectation (Fig. 2e).
A dynamic QUTE-CE scan was performed with 1m57s time-resolution. Total scan duration was ~1.5 hours, including 48min prior to NBOH-2C-CN challenge and ~52min of data featuring drug-induced CBV changes. NBOH-2C-CN primarily affect the cortex where 5-HT2A receptors exist in high density. CBV measurements from the full cortex were compared to a separate identical experiment with EPI acquisition. Absolute CBV was measured in the cortex using the dynamic UTE method (Fig. 3b). Relative CBV changes measured by EPI and UTE exhibit strong correlation of temporal features of the response and reasonable agreement in magnitude (Fig 3c).
DISCUSSION
Sparse radial sampling is being investigated to accelerate acquisition time for each UTE volume, thereby improving the dynamic frame rate. The apparent disadvantage of a T1-based method given the high r2/r1 ratio of ferumoxytol might well be mitigated in the context of slow frequency changes, such as when study pharmacological responses3. Similar effects are presumed to occur for ASL in relation to BOLD signal4. In analogy to ASL, which has smaller signal changes than BOLD, smaller absolute signal changes in T1-based methods might find application at low frequencies due to the absolute normalization, which could remove much of the drift.
CONCLUSION
To conclude, we achieved time-resolved functional imaging of brain vasculature in NHPs with a radial 3D UTE pulse sequence. Images do not exhibit spatial warping seen in EPI data and yields quantitative CBV measurements devoid of time-varying signal drift. Without baseline correction, the technique produces relative results that agree well with those obtained in a separate EPI experiment.
Acknowledgements
This work was supported in part by funding from NIH R01MH100350 (MDN) and by NIH T32EB013180 (GEF).
References
1. Gharagouzloo, C. A., Mcmahon, P. N. & Sridhar, S. Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences. Magnetic Resonance in Medicine (2014). doi:10.1002/mrm.25426.
2. Kim, Y. R., Rebro, K. J. & Schmainda, K. M. Water exchange and inflow affect the accuracy of T1-GRE blood volume measurements: Implications for the evaluation of tumor angiogenesis. Magn. Reson. Med. 47, 1110–1120 (2002).
3. Jenkins, B. G. Pharmacologic magnetic resonance imaging (phMRI): Imaging drug action in the brain. NeuroImage 62, 1072–1085 (2012).
4. Wang, J. et al. Arterial spin labeling perfusion fMRI with very low task frequency. Magn. Reson. Med. 49, 796–802 (2003).},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
PURPOSE
The three primary physiological indicators of neural activity in fMRI are changes in cerebral blood volume (CBV), blood flow and oxygenated state of hemoglobin.To isolate the CBV-induced signal change, T2*-weighted echo-planar imaging (EPI) sequences are commonly utilized with intravascular contrast agent to overshadow contrast from changes in blood oxygenation and enhance signal from CBV changes. While EPI sequences are fast, they are prone to significant distortion artifact. Additionally, macroscopic susceptibility artifacts confound the MR signal and are difficult to separate from baseline blood oxygenation level dependent (BOLD) effects; thus results are qualitative. Ultra-short time-to-echo (UTE) sequences are insensitive to susceptibility changes and extravoxular signal dephasing. Thus, we propose to use quantitative UTE contrast-enhanced (QUTE-CE) MRI to measure CBV changes dynamically.
METHODS
QUTE-CE MRI is the combination of acquisition with an optimized 3D UTE pulse sequence and an intra-vascular contrast agent1 to render a highly quantitative signal. Ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, Massachusetts, USA) was used for contrast.
Relaxation rates were measured in 1% heparinized whole-calf-blood (Fig. 1a,-c) and modeling with the spoiled gradient echo (SPGR) equation was used to determine optimized parameters for efficient dynamic scans (Fig. 1d). CBV is calculated by simple partial volume calculations. The effect of signal modification by vascular water molecule exchange is suppressed with low TR and high FA2. Modeling signal intensity with two compartments:
IM=fBIb+(1−fB)IT
where, IT is the brain tissue intensity, IB is the blood intensity and fB is the fraction of the voxel occupied by blood. For each image volume, CBV is calculated voxel-by-voxel by subtracting a pre-contrast image then scaling the results by the blood intensity as determined in a large vessel:
fB=CBV=I,M−IMI,B−IB
Animal experiments were conducted under an approved IACUC protocol. A dynamic QUTE-CE study was performed with ferumoxytol on a non-human primate (NHP) with NBOH-2C-CN, a potent and selective 5-HT2A receptor agonist, and results were compared to the current gold standard EPI + ferumoxytol imaging. All imaging was performed on a Siemens 3T Tim Trio magnet. NHPs were anesthetized throughout the scan with isoflurane (1-3%). EPI and UTE scans consisted of three imaging phases: pre-contrast followed by a bolus of 10mg/kg ferumoxytol post-contrast and then administration of 50 mcg/kg of NBOH-2C-CN. Single-shot EPI was accelerated in the phase-encode direction by a factor of two providing an isotropic spatial resolution of 1.3mm and TE=23ms.
RESULTS
QUTE-CE pre-contrast images rendered dark blood with a small amount of tissue contrast in NHPs (Fig. 2a). Bright positive contrast of the blood was achieved after injection of ferumoxytol (Fig. 2b-d). Vasculature was clearly visible and all parts of the anatomy were free of image warping (Fig 2a-c). In contrast, time-averaged EPI data equal to the duration of the dynamic UTE scan exhibited significant signal dropout in the anterior and posterior brain, with obvious image warping (Fig 2f). The same custom-built 8-channel receive coil was used in both acquisitions. Maps of absolute CBV obtained from pre- and post-contrast UTE images are of high quality and have quantitative values consistent with expectation (Fig. 2e).
A dynamic QUTE-CE scan was performed with 1m57s time-resolution. Total scan duration was ~1.5 hours, including 48min prior to NBOH-2C-CN challenge and ~52min of data featuring drug-induced CBV changes. NBOH-2C-CN primarily affect the cortex where 5-HT2A receptors exist in high density. CBV measurements from the full cortex were compared to a separate identical experiment with EPI acquisition. Absolute CBV was measured in the cortex using the dynamic UTE method (Fig. 3b). Relative CBV changes measured by EPI and UTE exhibit strong correlation of temporal features of the response and reasonable agreement in magnitude (Fig 3c).
DISCUSSION
Sparse radial sampling is being investigated to accelerate acquisition time for each UTE volume, thereby improving the dynamic frame rate. The apparent disadvantage of a T1-based method given the high r2/r1 ratio of ferumoxytol might well be mitigated in the context of slow frequency changes, such as when study pharmacological responses3. Similar effects are presumed to occur for ASL in relation to BOLD signal4. In analogy to ASL, which has smaller signal changes than BOLD, smaller absolute signal changes in T1-based methods might find application at low frequencies due to the absolute normalization, which could remove much of the drift.
CONCLUSION
To conclude, we achieved time-resolved functional imaging of brain vasculature in NHPs with a radial 3D UTE pulse sequence. Images do not exhibit spatial warping seen in EPI data and yields quantitative CBV measurements devoid of time-varying signal drift. Without baseline correction, the technique produces relative results that agree well with those obtained in a separate EPI experiment.
Acknowledgements
This work was supported in part by funding from NIH R01MH100350 (MDN) and by NIH T32EB013180 (GEF).
References
1. Gharagouzloo, C. A., Mcmahon, P. N. & Sridhar, S. Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences. Magnetic Resonance in Medicine (2014). doi:10.1002/mrm.25426.
2. Kim, Y. R., Rebro, K. J. & Schmainda, K. M. Water exchange and inflow affect the accuracy of T1-GRE blood volume measurements: Implications for the evaluation of tumor angiogenesis. Magn. Reson. Med. 47, 1110–1120 (2002).
3. Jenkins, B. G. Pharmacologic magnetic resonance imaging (phMRI): Imaging drug action in the brain. NeuroImage 62, 1072–1085 (2012).
4. Wang, J. et al. Arterial spin labeling perfusion fMRI with very low task frequency. Magn. Reson. Med. 49, 796–802 (2003).@article{sawantdeveloping,
title = {Developing superparamagnetic iron oxide nanoparticles as tumor-specific magnetic resonance imaging (MRI) contrast agents},
author = {RM Sawant and E Gultepe and D Nagesha and S Sridhar and VP Torchilin},
abstract = {Superparamagnetic iron oxide nanoparticles (SPION) have received increased interest due to their characteristic small size ca 4-10 nm and excellent T2-type MRI contrast properties. However, uncoated-“plain” SPION have a tendency to aggregate and thus are not stable at normal physiological conditions. In this work we load the SPION in polymeric polyethylene glycol phosphatidyl ethanolamine (PEG-PE) micelles and additionally surface-modify with anticancer anti-nucleosome antibody 2C5.(mAb 2C5). SPION-loaded PEG-PE micelles were stable with the size ranging from 20 to 40 nm. The conjugation of mAb 2C5 was gentle and there was almost no loss in activity of the antibody after conjugation. SPION-loaded mAb 2C5 immunomicelles were able to recognize and bind with human breast cancer MCF-7 cells in vitro significantly higher when compared to SPION-loaded “plain” micelles or SPION-loaded “non …},
keywords = {MRI},
pubstate = {published},
tppubtype = {article}
}
