Quantification and normalization of Cerebral Blood Flow in rat brain using Pseudo-continuous Arterial Spin Labeling with phase-contrast-based flow measurement at 7 Tesla.
Sankar Seramani1, Xuan Vinh To1, Sakthivel Sekar1, Boominathan Ramasamy1, Kishore Bhakoo1, and Kuan Jin Lee1

1Singapore Bioimaging Consortium, Singapore, Singapore

Synopsis

pCASL is a modified form of CASL where a short train of RF pulses reproduces CASL. pCASL sequence uses flow driven adiabatic pulses to invert the spin. The labeling efficiency of the pCASL sequence has a dependency on the velocity of the blood at the labeling. Phase contrast MRI (PCMRI) was used to measure the velocity of the blood at the labeling plane and to normalize the CBF value. In this study, we tested pCASL and PCMRI acquisition on a cohort of control rats vs. hyperglycemic rats and documented effect of varied labeling efficiency.

Introduction

pCASL is a modified form of CASL where a short train of RF pulses reproduces CASLproce. pCASL has been proven to show high SNR and multi-slice imaging capability without requiring a separate labelling coil as with CASL. The labeling efficiency of the pCASL sequence depends on the velocity of the blood during labeling [1-4]. Aslan et al have shown a simple way of measuring the labeling efficiency in-vivo using phase contrast MRI (PCMRI), which can be used to normalize the CBF value [1]. In this study, we tested the effect of normalizing the CBF with PCMRI on a cohort of control rats vs. hyperglycemic rats.

Materials and Methods

The study was approved by the IACUC of Biomedical Sciences Institutes, Singapore. All imaging was done on 7T Bruker Clinscan scanner with 72 mm volume transmit and 4 channel rat brain phased array coil. Seven male Wistar rats were used in this study (4 controls and 3 hyperglycemic). Hyperglycemia was induced by a single streptozotocin (STZ) injection (55mg/kg, IV) at week 7 and imaging was performed at week 14. To characterize hyperglycemia, blood glucose and HbA1c were measured from blood samples. The animals were initially anesthetized with 5% isoflurane in 5:1 Air:Oxygen mix at 1.2L/min, and maintained at 2-2.5% isoflurane during the scan. T1 mapping was calculated using inversion recovery single-shot spin echo EPI sequence with 7 inversion times from 10 to 8000ms); TR/TE= 10000/28msec, BW=3572 Hz/Pixel, NEX=2, FOV=40x30.4x21 mm, matrix size=100x76x14. ASL data with multi-slice pCASL sequence were collected with 14 slices (TE/TR =4000/28ms, post-labeling delays ranging from 0 to 600ms), with the same EPI sequence. Labeling plane was positioned 22mm from the center of the imaging slab. 200 inversion pulses were used with FA=25o with 200ms gaps, gradient strength=70mT/m. ECG and respiratory-triggered PCMRI images were collected at the level of the labeling plane carotid flow with the following parameters: velocity encoding=100cm/s, 10 phases per cardiac cycle, TR/TE/NA/FA = 13.30/3.84ms/6/10 degree. Total flow from PCMRI data was quantified using the automatic vessel tracking algorithm implemented in Segment [5]. Distortion correction for EPI images was performed using FSL TOPUP [6]. Cerebral blood flow (CBF) was quantified from pCASL using a general kinetic model [7]. Total flow quantified from pCASL data was calculated from the mean perfusion value of the whole brain, brain volume, and assumed specific density of 1.04g/ml . pCASL labeling efficiency was calculated using the method described in [1], and used to correct the CBF map.

Results and Discussions

Examples of T1 map, efficiency-corrected CBF map, and goodness-of-fit (R2) map is shown in Fig. 1. Whole-brain mean CBF and regional CBF from ROIs in the cortex and caudate putamen quantified from pCASL data before and after flow data correction are compared in Fig. 2. Details of PCMRI acquisition, flow data from pCASL and PCMRI, and labeling efficiency are summarized in Fig. 3. PCMRI results show the hyperglycemic group to have significantly lower flow compared to age-matched controls. Furthermore, labeling efficiency was strongly correlated with total carotid blood flow (Fig. 4). Uncorrected pCASL results appeared to show no difference. Larger differences in whole brain and regional CBF were observed, after correction with labeling efficiency calculated based on flow data from PCMRI. This suggests that calibrating for different labeling efficiency from scan to scan is important. The PCMRI-corrected CBF values were found to be several times higher than published values. However, the flow quantification was tested and calibrated with a flow phantom of known flow rate, and we consider the in-vivo PCMRI result to be reliable. Other possible sources of error, e.g. brain weights, were within expected values. One explanation for the higher perfusion might be the effect of a higher concentration of isoflurane, which is a vasodilator and permeates the blood-brain-barrier at the dose used; the recovery period is more than 1 hour, which was within the acquisition time frame [8].

Conclusion

Our results emphasize the importance of taking varying labeling efficiency into account. This can be done easily and quickly by acquiring an additional PCMRI scan which takes only a few minutes. In further work, different anesthetics, eg: ketamine-xylazine or medetomidine, will be used to confirm the effect of isoflurane on brain perfusion and carotid flow.

Acknowledgements

We would like to acknowledge the contributions of Dr. Danny JJ Wang and Dr. Kai-Hsiang Chuang for facilitating the pulse sequence for pCASL and technical/scientific inputs respectively.

References

[1] S.Aslan, et al., MRM. 2010;63:765. [2] L. Maccotta, et al., NMR in Biomedicine. 1997;10:216. [3] B.A.Moffat, et al., JMRI. 2005;21:290. [4]W. Wu, et al., MRM, 2007; 58:1020. [5] http://segment.heiberg.se;’ S.Bidhult, et al., Proceedings of Seventeenth Annual SCMR Scientific Session, New Orleans, USA, 2014. [6] J.Andersson, et al., Neuroimage, 2003;20:870. [7] R.Buxton, MRM, 1998; 40:383. [8] Tetrault, et al., European Journal of Neuroscience, 2008; 28:1330.

Figures

Figure 1: T1, corrected CBF and R2map of rat brain at different slices of a control rat

Figure 2: Perfusion measurement before and after PCMRI based flow correction

Figure 3: Phase Contrast MRIbased velocity measurement in the carotid artery

Figure 4: Correlation between the labeling efficiency and total carotid blood flow measure by PCMRI



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
3342