WSO - January 2024 - 10

10
International Journal of Stroke 19(1)
such as DIR and 3D-MRI to improve the detection rate of
cortical-CMIs in-vivo. DIR images have been reported to
have better intracortical localization than conventional
MRI,28 and 3D-MRI is superior to 2D-MRI in terms of spatial
resolution.29 Therefore, more and more studies have
used 3D-DIR combined with 3D-FLAIR images in detecting
cortical-CMIs instead of conventional 2D-MRI.6,10,30-32
However, the longer scan time required for 3D-MRI scan
has restricted its use in clinical practice.
Iron accumulation in cortical-CMI lesions can increase
their detectability on MRI, especially with iron-sensitive
MRI sequences such as susceptibility weighted imaging
(SWI) or T2*-weighted images.14 Some cortical-CMIs that
are undetectable on T1- and T2-weighted images may be
visible on these sequences due to iron accumulation in the
microinfarct core.7 Therefore, SWI or T2*-weighed images
can provide complementary information for detecting cortical-CMIs
beyond T1- and T2-weighed images and
improve the detection rate.7
These findings demonstrate the potential of new neuroimaging
strategies to detect more cortical-CMIs in-vivo
and emphasize the need to develop techniques with higher
sensitivity and specificity. Moreover, visual ratings of cortical-CMIs
on MRI are time-intensive and operator-dependent,
making automated methods for detection necessary to
support large-scale studies.
Identification and evolution of ISDPLs
ISDPLs are small hyperintense lesions on DWI, with corresponding
hypointense or isointense signals on apparent
diffusion coefficient maps.3 ISDPLs overlap with recent
small subcortical infarcts and acute cortical microinfarction
(<5 mm in diameter)3 and can be mostly observed in subcortical
white matter, followed by cortical gray matter and
then the deep gray matter.33
Although DWI has high sensitivity in detecting ISDPLs
of 1-2 mm in diameter,34 it is unable to capture the entire
burden of such lesions in the brain. However, submillimeter
DWI has shown promise in detecting smaller lesions that
are invisible on conventional DWI.35 Moreover, detecting a
single ISDPL on DWI may suggest an annual incidence of
several hundred new lesions in the brain.36
ISDPLs typically disappear on DWI within 2 weeks and
may evolve into other chronic lesions or disappear on follow-up
FLAIR or T2-weighted images.37 A previous study
has reported that 58.8% of ISDPLs appeared as WMHs on
follow-up MRI, 17.6% developed cavitation, 5.9% became
old cortical-CMIs, and 17.6% disappeared after a mean
follow-up of 4.7 years.33 A possible reason for disappearance
of these lesions on follow-up imaging might be due to
salvageable tissue which can undergo tissue repair and lead
to their disappearance.38 Besides, it has been reported that
the lesions visible on follow-up imaging tend to be larger
initially and the smaller lesions tend to disappear or become
International Journal of Stroke, 19(1)
undetectable due to limited image resolution.39 Moreover,
another study has shown that some lesions invisible on
follow-up T2-weighted images appeared as hypointense
signals on SWI sequences, indicating a probable hemorrhagic
transformation.7
ISDPLs are more commonly observed in patients with
acute intracerebral hemorrhage (ICH) compared to the general
population40 and were indeed shown to be acute microinfarction
on histology in CAA-related ICH.41 ISDPLs
following acute ICH are associated with microangiopathy
such as WMH and cerebral microbleeds (CMBs) as well as
ICH characteristics such as hematoma volumes.42,43 Based
on current findings, it is likely that ISDPLs after ICH are
primarily a consequence of the progression of cerebral
small vessel disease (CSVD) and are influenced by secondary
risk factors associated with ICH, such as intensive
blood pressure reduction, cerebral blood flow (CBF) dysregulation,
inflammation, and blood-brain barrier leakage.42,43
Further investigations are necessary to elucidate
the intricate interactions among these mechanisms in the
development of ISDPLs.
Risk factors of cortical-CMIs
The association of cortical-CMIs with traditional cardiovascular
risk factors (e.g. hypertension, hyperlipidemia,
and diabetes) has been widely studied in recent years, but
the results have been inconsistent.20 Many studies have
demonstrated that the presence of cortical-CMIs was associated
with
hypertension44,45
or
hyperlipidemia5,46
or
both.25,47,48
By contrast, some studies showed no relationship
between cortical-CMIs and cardiovascular risk factors.20,26,49
For example, one study investigating the risk
factors of cortical-CMIs on 7 T MRI reported that the risk
of cortical-CMIs did not change with the presence of hypertension,
hyperlipidemia, or diabetes.20 Moreover, only a
few animal experiments have shown the temporal relationship
between cardiovascular risk factors and incident cortical-CMIs,50
which, however, has not been verified
human studies yet.
in
MRI correlates of cortical-CMIs
Many studies have shown that the presence of cortical-CMIs
was associated with MRI markers of CSVD such as lacunes,5,6,9,51
WMH,9,25,26,52,53 CMBs,9,25,31,48,53 and brain atrophy,5,6,25,27,44,53
indicating a shared etiology such as CAA and
arteriolosclerosis. It has been reported that CAA is highly
related to the occurrence of CSVD including lobar lacunes,54,55
WMH,56 CMBs,10 and cortical-CMIs,57 while arteriolosclerosis
also contributes to the pathogenesis of CSVD
albeit in a different manner.58 Moreover, a study found that
the presence of cortical-CMIs was significantly associated
with total MRI burden of CSVD in CAA indicating more
severe changes in CAA-related vascular pathology.32
WSO - January 2024

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