SEOKHA JIN1 and HyungJoon Cho2
1UNIST, Ulsan, Korea, Republic of, 2Ulsan, Korea, Republic of
Synopsis
Dynamic susceptibility
contrast MRI (DSC MRI) is widely used for cerebral blood flow (CBF) measurement
for diseases, such as stroke and cancer.1-2 Fundamental assumption
of DSC-MRI based CBF measurement is that contrast agent is non-leaking with
intact blood brain barrier (BBB).3 Here, we investigate the effect
of BBB disruption on the CBF measurement, especially for stroke model utilizing
serial dual acquisitions using DOTAREM and SPION. As SPION remains as
intravascular agent, while DOTAREM becomes extravasating agent with BBB
disruption, dual CBF acquisitions with both agents provide quantitative way to
characterize the effect of BBB disruption on CBF measurements with DSC-MRI.Purpose
To experimentally and
theoretically investigate the effect of BBB disruptions on the CBF measurement
with DSC-MRI acquisition, especially for stroke model with MCAO reperfusion, dual
acquisitions using DOTAREM and SPION were sequentially acquired. Observed
experimental temporal signal behavior of DSC-MRI were verified using Monte
Carlo simulation of
T1 and
T2* effects in the
presence of leaking contrast agent.
Method
Experimental
study was performed at Bruker 7T scanner using two different contrast agents of
DOTAREM and SPION for two groups of animals.
Experimental
group (
n=4): For BBB disrupted model,
SD rats went through 1h MCAO and 24h reperfusion.
4 DOTAREM was
injected via tail IV at the dose of 0.3 mmol/kg. After 4 hours later, MION was
injected at the dose of 0.075 mmol/kg. Infarction area and BBB disruption was
evaluated by ADC map and
T1
difference map before and after DOTAREM injection, respectively.
Control
group (
n=4): Normal SD rats were
experimented to verify if CBF measurements with DOTAREM and SPION provide same information
in the case of intact BBB.
For
DSC-MRI acquisitions, gradient echo EPI sequence was used with matrix size = 96×96,
field of view = 30×30 mm
2, repetition time (TR) = 300ms, echo time
(TE) = 17ms.
Theoretical
study was also performed to understand the effect of leaking contrast on the
signal behavior from DSC-MRI with varying degree of BBB disruption using Monte
Carlo simulations.
5Result
Control group showed
strong correlation (R
2=0.9173) between SPION- and DOTAREM-derived
CBF for normal brain as shown in Figure 1. For experimental group, CBF from
SPION was ~1.3 times faster than that from DOTAREM for ipsilateral hemisphere
with disrupted BBB, while similar CBF was measured for contralateral hemisphere
as shown in Figure 2. Simulation shows the signal behavior of DSC-MRI with
increasing BBB disruption for
T1
(Figure 3a),
T2* (Figure
3b), and combined effect (Figure 3c), respectively. It is observed that with
increasing BBB disruption, i.e., increasing Ktrans values, both
T1 and
T2* effects contribute toward enhancing the signal of
DCE-MRI, which will result in reducing the CBF values for the region of leaking
contrast agent.
Conclusion
and discussion
DSC-MRI is a powerful
technique for evaluating CBF. However, we observed both from experiments and
simulations that CBF values are underestimated when contrast agent starts to
leak through disrupted BBB from combined
T1
and
T2* effects. It is interesting
to notice that the level of underestimation is proportional to the value of Ktrans. Dual DSC-MRI acquisitions
using DOTAREM and SPION may become more sensitive way to quantify the BBB
integrity than conventional DCE-MRI, because the first-pass signal of DSC-MRI
is more directly affected by BBB integrity (Ktrans), rather than by
interstitial volume (Ve).
Acknowledgements
This work was supported by the National Research Foundation of Korea Grants funded by the Korean Government (No. 2010-0028684 and No. 2014 R1A1A1 008255)References
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