Quantitative vascular imaging with QUTE-CE MRI
Codi Gharagouzloo1, Ju Qiao2, Liam Timms3, Aniket Pandya3, Praveen Kulkarni4, Craig Ferris5, and Srinivas Sridhar3

1Bioengineering, Northeastern University, Boston, MA, United States, 2Industrial Engineering, Northeastern University, Boston, MA, United States, 3Physics, Northeastern University, Boston, MA, United States, 4Northeastern University, Boston, MA, United States, 5Center for Translational Neuroimaging (CTNI), Northeastern University, Boston, MA, United States


We demonstrate a unique type of vascular imaging using ferumoxytol as an iron-oxide nanoparticle contrast agent (CA) and a 3D ultra-short TE (UTE) pulse sequence. The raw UTE signal intensity is shown to be quantitative by comparison to excised blood immediately after imaging with n=5 Sprague Dawley rats. In this preliminary study, we calculate the cerebral blood volume (CBV) on a regional basis using a 174-region anatomic atlas that is consistent among animals and is independent of CA concentration.


The purpose of this research is to develop quantitative positive contrast imaging techniques exploiting ultrasmall superparamagnetic iron-oxide nanoparticles (USPIONs) as a positive contrast agent (CA). Ferumoxytol is currently the only magnetic USPION nanoplatform that is FDA approved and commercially available, albeit it’s approval is for iron deficiency anemia (IDA), and it is therefore an attractive CA for clinical translation. Ferumoxytol is currently being utilized, or has been utilized, in clinical trials with standard T1 and T2 imaging sequences for prostate cancer and gliomas and also in MR angiography[1]. However ultrashort TE (UTE) 3D imaging allows for positive contrast with high CNR and, utilizing TE’s in microseconds rather than the typical millisecond regime for negative contrast imaging modalities[2]. This preliminary work is an extension to our previously published work (MRM 2014 [2]), in which we demonstrate that the effectiveness for obtaining sharpT1-weighted images of rat vascular with a quantitative signal utilized to measure the cerebral blood volume (CBV). The long-term goal of this research is to provide an effective means of mapping brain vascularity to change the way neurodegenerative diseases are diagnosed[3].


Previously, we developed an imaging technology in our lab, called quantitative contrast-enhanced ultra-short time-to-echo (QUTE-CE) MRI[2]. We utilize a 3D radial UTE pulse sequence with ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, Massachusetts, USA) to produce purely T1-weighted positive-contrast images in which signal intensity predicted with unprecedented accuracy by the SPGR equation as a function of CA dosage. We applied this imaging modality to 5 Sprague Dawley rats with a range of clinically relevant blood concentrations (~50-200ug/ml) and visualized the cerebral vasculature. We then quantified the CBV with a simple two volume model for blood and tissue. Ferumoxytol was administered just prior to imaging MRI images were obtained using a Bruker Biospec 7.0T/20-cm USR horizontal magnet (Bruker, Billerica, Massachusetts, USA) and a 20-G/cm magnetic field gradient insert (ID=12 cm) capable of a 120-µs rise time (Bruker). Rats were anesthetized (2-3% isoflurane) during imaging.


Pre-contrast injection rendered UTE images with most vasculature and anatomical structure void of signal (Fig. 1a,b), with time-of-flight (ToF) effects limited to the image periphery. Post-contrast images reveal clearly delineated vasculature. The pre-contrast brain appears featureless with nominal background signal intensity. The post-contrast brain is then evaluated for CBV and compared between animals.


This data implies that QUTE-CE imaging can be explored for quantitative mapping of the brain vasculature. Pre-contrast UTE imaging reveals that flow effects are limited to blood entering into the image space over only a finite distance, which are not present in the brain. Acquiring images in micro-seconds after excitation allowed for contrast inversion and elimination intervoxular susceptibility artifacts and a quantitative of raw signal intensity.


Further development of this modality for quantitative CBV mapping could provide a simple and direct measure of CBV that can be compared between animals or patients without need for a relative comparison.


No acknowledgement found.


[1] T. Christen, W. Ni, D. Qiu, H. Schmiedeskamp, R. Bammer, M. Moseley, and G. Zaharchuk, “High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol.,” Magn. Reson. Med., vol. Im, pp. 705–710, 2012.

[2] C. A. Gharagouzloo, P. N. McMahon, and S. Sridhar, “Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences.,” Magn. Reson. Med., doi: 10.1002/mrm.25426, Aug. 2014.

[3] C.-C. V Chen, Y.-C. Chen, H.-Y. Hsiao, C. Chang, and Y. Chern, “Neurovascular abnormalities in brain disorders: highlights with angiogenesis and magnetic resonance imaging studies.,” J. Biomed. Sci., vol. 20, p. 47, 2013.


(a) Pre-contrast QUTE-CE image of a Sprague Dawley rat head (b) Post-contrast image and (c) segmented brain. Acquisition parameters for all images are as following: 3D Radial UTE; FOV 3×3×3cm3; matrix mesh size 200×200×200; TE 13 µs; TR 3.5 ms; and q= 20°.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)