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
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