Dynamic Contrast-Enhanced MRI in Mice at High Field: Estimation of the Arterial Input Function Can be Achieved by Phase Imaging A.-C. Fruytier, 1 J. Magat, 1 F. Colliez, 1 B. Jordan, 1 G. Cron, 2 and B. Gallez 1 * Purpose: Quantitative dynamic contrast-enhanced MRI requires an accurate arterial input function (AIF). At high field, increased susceptibility effects and decreased longitudinal relaxivity of contrast agents lead to predominant T 2 * effects in blood vessels, producing a dip in signal during passage of the contrast agent bolus. This study determined phase-derived AIFs in mice at 11.7 T. Methods: AIFs were measured in aorta/vena cava for five FBV/N mice and in iliac arteries/veins for five NMRI mice with a fast low angle shot sequence, simultaneously with tumor imaging (temporal resolution: 1.19 s). Gadoterate was injected into the tail vein as a bolus (0.286 mmol Gd/kg). An in vitro study was also performed to calculate the relationship between DF and gadolinium concentration. Results: The phantom system confirmed the linear relationship between measured DF and gadolinium concentration. In vivo, a dip in arterial magnitude signal made it impossible to quan- tify the AIF. With phase imaging, a clear quantifiable bolus peak was obtained; peak measured concentration in plasma was 4.9 6 0.9 mM for FBV/N mice and 8.0 6 0.6 mM for NMRI mice, close to the expected concentration of 6.8 mM. Conclusion: Phase imaging seems to be an appropriate means to measure the AIF of mice at high field. Magn Reson Med 71:544–550, 2014. VC 2013 Wiley Periodicals, Inc. Key words: arterial input function; dynamic contrast-enhanced MRI; mice; high field; phase imaging Ultra-high-field magnetic resonance imaging and spec- troscopy are invaluable tools in cancer research. These technologies enable characterization of the tumor micro- environment with high signal-to-noise ratio and high spectral resolution. Dynamic contrast-enhanced (DCE)- MRI allows noninvasive investigation of tumor hemody- namics and early monitoring of the effects of antivascu- lar and antiangiogenic drugs. For the determination of quantitative parameters through pharmacokinetic model- ing, the arterial input function (AIF), defined as the time-dependent contrast agent concentration in the ves- sels feeding the tumor, should be measured. The acquisi- tion of an individual AIF simultaneous with tumor imaging offers several advantages over a population-aver- aged AIF. Individually measured AIFs account for varia- tions in injection rate, dose, and cardiac output and therefore potentially allow more accurate modeling (1). Nevertheless, population-averaged AIFs are often pre- ferred due to difficulties balancing temporal and spatial resolution. 11.7 T provides greater signal-to-noise ratio and conse- quently a possible reduction of acquisition time. There- fore, we can obtain sufficiently high DCE-MRI temporal and spatial resolution to enable measurement of the ini- tial AIF bolus peak in small arteries in mice. However, the main challenge of AIF measurements at high field using DCE-MRI is increased susceptibility effects. Indeed, the intravascular compartmentalization of con- trast agent produces strong susceptibility gradients (2), largely increased at 11.7 T, leading to major T 2 * effects in blood vessels. Additionally, there is a decrease of lon- gitudinal relaxivity (r 1 ) at high field. This decrease in r 1 is not dramatic for commercial extracellular agents (3,4). For example, for gadoterate meglumine the decrease is about 25% at 11.7 T compared with 1.5 T. However, for contrast agents with protein binding or slow rotational motion, the longitudinal relaxivity can be severely reduced at high field (3), necessitating the use of higher doses and therefore leading to accentuated T 2 * suscepti- bility effects. MR images are complex; they contain magnitude and phase information. Earlier work has suggested that phase imaging can more reliably characterize the AIF, due to phase’s linear relationship with concentration (without contamination from T 1 or T 2 effects), greater signal-to- noise ratio, lower sensitivity to inflow effects, hematocrit independence and reduced vulnerability to partial vol- ume effects (5–9). Only a few studies have attempted AIF measurements from the DCE-MRI phase signal. To our knowledge, no AIF study in mouse arteries has ever been reported at fields higher than 4.7 T. A recent study measured the vascular input function in the left ventricle of mice at 7 T (10). In this work, magnitude and phase imaging were evaluated for measuring AIFs in mice at 11.7 T, simul- taneously with tumor imaging. Two types of mice were used: FVB/N and NMRI mice where the AIF was taken from aorta/vena cava and iliac arteries/veins, respec- tively. The AIF was modeled with a bi-exponential function to yield AIF parameters (11–13). To validate the phase technique, an in vitro study with a phantom consisting of tubing mimicking a mouse vessel was also conducted. 1 Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universit e Catholique de Louvain, Brussels, Belgium. 2 Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada. Grant sponsor: Foundation against Cancer. *Correspondence to: Bernard Gallez, Ph.D., REMA, Avenue Mounier 73, boite B1.73.08, B-1200 Brussels, Belgium. E-mail: bernard.gallez@uclouvain.be Received 11 July 2012; revised 11 January 2013; accepted 20 January 2013 DOI 10.1002/mrm.24682 Published online 25 February 2013 in Wiley Online Library (wileyonlinelibrary.com). Magnetic Resonance in Medicine 71:544–550 (2014) VC 2013 Wiley Periodicals, Inc. 544