In
stroke care, the extent of irreversible brain injury, termed infarct
core, plays a key role in determining eligibility for acute treatments,
such as intravenous thrombolysis and endovascular reperfusion therapies.
Many of the pivotal randomized clinical trials testing those therapies
used MRI Diffusion-Weighted Imaging (DWI) or CT Perfusion (CTP) to
define infarct core. Unfortunately, these modalities are not available
24/7 outside of large stroke centers. As such, there is a need for
accurate infarct core determination using faster and more widely
available imaging modalities including Non-Contrast CT (NCCT) and CT
Angiography (CTA).
Prior studies have suggested that
CTA provides improved predictions of infarct core relative to NCCT;
however, this assertion has never been numerically quantified by
automatic medical image computing pipelines using acquisition protocols
not confounded by different scanner manufacturers, or other protocol
settings such as exposure times, kilovoltage peak, or imprecision due to
contrast bolus delays. In addition, single-phase CTA protocols are at
present designed to optimize contrast opacification in the arterial
phase. This approach works well to maximize the sensitivity to detect
vessel occlusions, however, it may not be the ideal timing to enhance
the ischemic infarct core signal (ICS).
In this work,
we propose an image analysis pipeline on CT-based images of 88 acute
ischemic stroke (AIS) patients drawn from a single dynamic acquisition
protocol acquired at the acute ischemic phase. We use the first scan at
the time of the dynamic acquisition as a proxy for NCCT, and the rest of
the scans as a proxy for CTA scans, with bolus imaged at different
brain enhancement phases. Thus, we use the terms “NCCT” and “CTA” to
refer to them. This pipeline enables us to answer the questions “Does the injection of bolus enhance the infarct core signal?” and “What is the ideal bolus timing to enhance the infarct core signal?”
without being influenced by aforementioned factors such as scanner
model, acquisition settings, contrast bolus delay, and human reader
errors. We use reference MRI DWI images acquired after successful
recanalization acting as our gold standard for infarct core.
The
ICS is quantified by calculating the difference in intensity
distribution between the infarct core region and its symmetrical healthy
counterpart on the contralateral hemisphere of the brain using a metric
derived from information theory, the Kullback-Leibler divergence (KL
divergence). We compare the ICS provided by NCCT and CTA and retrieve
the optimal timing of CTA bolus to maximize the ICS.
In
our experiments, we numerically confirm that CTAs provide greater ICS
compared to NCCT. Then, we find that, on average, the ideal CTA
acquisition time to maximize the ICS is not the current target of
standard CTA protocols, i.e., during the peak of arterial enhancement,
but a few seconds afterward (median of 3 s; 95% CI [1.5, 3.0]). While
there are other studies comparing the prediction potential of ischemic
infarct core from NCCT and CTA images, to the best of our knowledge,
this analysis is the first to perform a quantitative comparison of the
ICS among CT based scans, with and without bolus injection, acquired
using the same scanning sequence and a precise characterization of the
bolus uptake, hence, reducing potential confounding factors.
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