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Page 2 of 10 Inoue et al. Vessel Plus 2021;5:11 I http://dx.doi.org/10.20517/2574-1209.2020.99

pathological conditions of the ischemic blood flow. Unfortunately, the COVID-19 pandemic has changed
the world’s landscape and made a detailed neurological examination more difficult than ever. In particular,
automated diagnostic imaging methods powered by artificial intelligence became more essential than ever
[1,2]
before. After the publication of positive endovascular therapy (EVT) trials in 2015 , or some people might
[3]
say from 2012 , perfusion imaging has become more popular and considered as a tool for therapeutic time
expansion. Along with the unique use of conventional sequences such as diffusion-weighted image - fluid-
attenuated inversion recovery (DWI-FLAIR) mismatch, the therapeutic window for acute ischemic stroke
has expanded in these few years.

The history of perfusion imaging
[4]
The concept of perfusion imaging was first described in 1980 , and over the next 40 years, perfusion
imaging has become a tool used regularly for strokes for analyzing the blood flow conditions.

Perfusion imaging was routinely used as a marker of tumor lesions in the central nervous system by
neurologists/neurosurgeons, enabling the differentiation of neoplasm from mass and the ability to
distinguish the radiation necrosis from the tumor growth.

The estimation of cerebral blood flow was mainly done using positron emission tomography (PET) in
[5]
the late 1960s ; and in the 1970s, the method turned out to be a gold standard for cerebral circulatory
metabolic function in the human brain. In the 1980s, the basic concept of cerebral circulatory metabolism
[6,7]
using PET and quantifying blood flow was established . The previous depictions and studies for
estimating cerebral blood flow were invasive using animal models, and it was essential to consider non-
invasive methods for clinical application to humans. From that perspective, PET could estimate parameters
such as cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF), and
cerebral metabolic rate of oxygen (CMRO ) non-invasively and repetitively compared to endovascular
2
angiography. From these studies, a PET study in the subacute onset of stroke could estimate that brain
[8]
tissue with CBF of less than 26 mL/100 g/min (in gray matter) and 12 mL/100 g/min (in white matter)
or CMRO of less than 65 mmol/100 g/min would turn into an ischemic tissue in several hours after the
2
onset which can be confirmed by computed tomography (CT) scans. Before this phase, the ischemic brain
tissue status, such as call penumbra, could be defined as which CBF is decreased, OEF is increased in
compensation, and CMRO is maintained at an average quantity.
2

Analysis of penumbral imaging along with the ischemic core
PET has long been used as the main axis of non-invasive clinical examinations in the analysis of penumbral
imaging, but only in the subacute phase of stroke. Therefore, the rapid investigation and use of penumbral
imaging have been warranted in the emergency field. Along with the penumbral pattern in acute ischemic
stroke, the ischemic core evaluation was showing progress.

[9]
In 1985 when the diffusion-weighted image (DWI) was first reported by Le Bihan et al. , this sequence
was used clinically to visualize cytotoxic cerebral edema in brain tissues. Cytotoxic edema represents the
corruption of ATP-dependent sodium/potassium membrane pumps. When cerebral ischemia occurs,
autolysis begins, followed by proteolysis. The osmotic pressure in the brain cells expands due to increased
[10]
intracellular water molecules, resulting in edema visualization. Moseley et al. first reported the usage of
ischemic brain tissues in humans in 1995, and this was thought to be one of the paradigm shifts in acute
stroke imaging.

DWI is overwhelmingly superior to non-contrast CT in identifying ischemic cores around the penumbra,
and with DWI it is possible to visualize acute infarct lesions more than the early CT signs [11-13] obtained by
CT, with both higher sensitivity and specificity. It overwhelms imaging examinations and can detect acute