Velocity-Selective Tip-Back Excitation for Hyperpolarized [13C] Urea Cardiac Perfusion Imaging
Maximilian Fuetterer1, Julia Busch1, Constantin von Deuster1,2, Christian Binter1, Nikola Cesarovic3, Miriam Lipiski3, Christian Torben Stoeck1,2, and Sebastian Kozerke1,2

1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, 2Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 3Division of Surgical Research, University Hospital Zurich, Zurich, Switzerland

Synopsis

A velocity-selective excitation scheme with bipolar slice-select gradients for hyperpolarized cardiac perfusion imaging is presented. Using the approach, an excitation ratio of >5 of myocardial signal to left-ventricular blood pool signal can be achieved based on differences in blood and tissue velocities. Thereby increased myocardial signal and reduced left-ventricular signal spilling is obtained. Dynamic perfusion images acquired with hyperpolarized [13C]urea in pigs show higher SNR and less signal leakage in the myocardium relative to a conventional excitation approach.

Introduction

Metabolically inert hyperpolarized [13C]-labeled substrates such as [13C]urea or HP001 have been used to investigate tumor, renal and cardiac perfusion (1–3). Due to its nontoxicity, [13C]urea is a promising compound for cardiac perfusion imaging in patients with impaired renal function or other contra-indications for Gadolinium. Achieving sufficiently high spatial and spectral resolution in large animals and humans, however, is challenging due to the limited [13C]urea polarization and the relatively short relaxation time in combination with low heart rates. Excitation of the large blood compartments of the heart strongly saturates the hyperpolarized signal before it arrives in the myocardium and causes significant signal leakage into the myocardium. To address these issues, a velocity-selective binomial excitation scheme is presented to improve image quality in hyperpolarized cardiac perfusion imaging.

Theory

For a given velocity $$$v_{enc}$$$ the accumulated phase of moving spins subject to a bipolar gradient pair can be set to π by adjusting the duration $$$T$$$ of a single gradient lobe and its area $$$A$$$ according to:

$$\gamma A T v_{enc} = π$$

When combined with a binomial 1-1 excitation, this effect can be exploited to tip back the magnetization of spins moving with $$$v_{enc}$$$ with the second RF pulse, whilst exciting stationary spins twice. For through-plane motion the bipolar gradients can be efficiently integrated into the slice selection scheme as illustrated in Fig-1. This excitation can be combined with any single-shot readout.

Methods

The velocity-sensitive excitation scheme was implemented into a dynamic, cardiac-triggered single-shot EPI sequence on a 3T Philips Ingenia system equipped with a four-channel 13C transmit/receive coil. Three healthy female pigs (30-35kg) were anesthetized (isoflorane 2-3%), ventilated (4-5L/min) and venous catheters for medication and injection of hyperpolarized substances were introduced. Pharmacological stress was induced by administration of dobutamine with a target heart rate of 120bpm. All experiments were performed in accordance with the Swiss Animal Protection Law and Ordinance.

Prior to in-vivo imaging, the proposed sequence was validated on a 2-compartment water flow phantom with a constant velocity of 48.5 cm/s and a series of different $$$v_{enc}$$$ encodings from 25cm/s to 80cm/s. Measurements were compared to simulated signal intensities obtained from Bloch simulations (Fig-2).

In-vivo, 2D anatomical and flow cine scans were acquired to determine through-plane blood velocities and appropriate trigger delays (Fig-3). An early diastolic heart phase was chosen to ensure both high blood velocities and mostly stationary myocardium. Two $$$v_{enc}$$$ encodings (100cm/s and 25cm/s) were used to measure left-ventricular (LV) and myocardial velocities and the timing of the velocity-sensitive excitation pulse for hyperpolarized perfusion imaging was adjusted accordingly.

For perfusion imaging, a 6.7M [13C]urea glycerol solution was doped with 18.5mM trityl radical and polarized in a commercial GE SpinLab Hyperpolarizer. 20ml of 200mM [13C]urea solution were injected over 4s into the femoral vein after dissolution and transport in a magnetic carrier device (4). Image acquisition was started 8 heart beats after the beginning of injection to avoid signal saturation inside the right ventricle. Sequence parameters were chosen as: FOV 110x110mm2, in-plane resolution 3x3mm2 (reconstructed to 1x1mm2), slice thickness 15mm, partial Fourier factor 0.65, flip-angle 60° resulting in an effective TE of 10.2/12.5ms (conventional/velocity-selective excitation). One image per heart beat was acquired for 60s during breath-hold.

Perfusion curves were extracted for septal and lateral regions of the myocardium and peak myocardial SNR was calculated.

Results

Sequence validation in the flow phantom showed good agreement of the excitation pattern with simulated signal intensities for different $$$v_{enc}$$$ encodings (Fig-2).

In-vivo, measured velocities in the early diastolic phase were 38-47 cm/s (LV) and 2.5-7.0 cm/s (myocardium), resulting in effective relative excitation of 0-20% (LV) and 97.7-99.7% (myocardium). Accordingly, an excitation ratio of myocardium-to-LV of >5 for a $$$v_{enc}$$$ of 42.5 cm/s was achieved (Fig-3).

Peak SNR in the myocardium with the velocity-selective vs. the conventional scheme was 47.4±6 (lateral), 41.3±16.3 (septal) vs. 23.9±6.2 (lateral), 13.8±6.8 (septal), respectively. Signal-time curves obtained with the velocity-selective scheme showed the expected physiological delay between LV and myocardial bolus arrival while the conventional scheme results in contaminated myocardial signal (Fig-5).

Discussion

The proposed velocity-selective tip-back excitation significantly increased myocardial SNR during bolus passage by preserving magnetization and reducing the effective excitation in the blood pool, thereby also minimizing signal spillage and contamination of the myocardial perfusion curves.

Due to the sharp excitation profile around $$$v_{enc}$$$, deviations from the nominal mean blood velocity result in residual blood pool signal at the boundary between LV and myocardium and the RV where velocities are less homogeneous (Fig-4).

Conclusion

The presented velocity-selective excitation scheme improves image quality and SNR in hyperpolarized cardiac perfusion imaging.

Acknowledgements

This work was supported by the Molecular Imaging Network Zurich (MINZ) and UK EPSRC (EP/I018700/1).

References

1. Von Morze C, Larson PEZ, Hu S, Yoshihara H a I, Bok R a., Goga A, Ardenkjaer-Larsen JH, Vigneron DB. Investigating tumor perfusion and metabolism using multiple hyperpolarized 13C compounds: HP001, pyruvate and urea. Magn. Reson. Imaging [Internet] 2012;30:305–311. doi: 10.1016/j.mri.2011.09.026.

2. Durst M, Koellisch U, Gringeri C, Janich M a., Rancan G, Frank A, Wiesinger F, Menzel MI, Haase A, Schulte RF. Bolus tracking for improved metabolic imaging of hyperpolarised compounds. J. Magn. Reson. [Internet] 2014;243:40–46. doi: 10.1016/j.jmr.2014.02.011.

3. Lau AZ, Miller JJ, Robson MD, Tyler DJ. Cardiac perfusion imaging using hyperpolarized 13 c urea using flow sensitizing gradients. Magn. Reson. Med. [Internet] 2015;00:n/a–n/a. doi: 10.1002/mrm.25713.

4. Shang H, Skloss T, von Morze C, Carvajal L, Van Criekinge M, Milshteyn E, Larson PEZ, Hurd RE, Vigneron DB. Handheld electromagnet carrier for transfer of hyperpolarized carbon-13 samples. Magn. Reson. Med. [Internet] 2015;00:n/a–n/a. doi: 10.1002/mrm.25657.

Figures

Figure 1: Sequence diagram including velocity-selective tip-back excitation. Bipolar gradient areas A with duration T are depicted in grey. The distance T is lower bound by the maximum gradient strength available.

Figure 2: top: Magnitude single-shot EPI images of flow phantom with constant flow velocity of 48.5 cm/s in the circular area. Encoding with $$$v_{enc}=velocity/2$$$ results in a phase of 2π, which is equivalent to the reference excitation with higher T2* weighting. bottom: Comparison of measurements with varying $$$v_{enc}$$$ and Bloch simulations.

Figure 3: top: ROI placement for through-plane velocity measurements under stress conditions on CINE and flow images. bottom: Measured through-plane velocities during dobutamine induced stress for left and right ventricular blood pool (LV/RV) as well as septal and lateral myocardium (SEP/LAT). Imaging heart phase is indicated by blue arrow.

Figure 4: [13C] urea perfusion images for three different time points after injection (see Fig-5). Conventional excitation (left column) is compared to velocity-selective excitation (right column). SNR at myocardial bolus peak is strongly increased with the velocity-selective method, with visibly increased image quality in the myocardium.

Figure 5: Example perfusion curves (SNR normalized). left: septal and lateral myocardial segments on CINE scan. center,right: LV and myocardial signal-intensity curves for velocity-selective (center) and conventional (right) excitation. Imaging time-points from Fig-4 are highlighted in grey.



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