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Recent advances in magnetic
resonance imaging for stroke diagnosis
Radhika Rastogi, Yuchuan Ding, Shuang Xia1, Meiyun Wang2, Yu Luo3, Hyun Seok Choi4,
Zhaoyang Fan5, Meng Li6, Timothy D Kwiecien, Ewart Mark Haacke6,7,8,9

Website:
http://www.braincirculation.org
DOI:
10.4103/2394-8108.164996
Departments of
Neurological Surgery
and 6Radiology, Wayne
State University,
School of Medicine,
Detroit, Michigan,
5
Department of Biomedical
Sciences, Biomedical
Imaging Research
Institute, Cedars-Sinai
Medical Center, Los
Angeles, California,
USA, 1Department of
Radiology, Tianjin First
Central Hospital, Tianjin,
2
Department of Radiology,
Henan Provincial People’s
Hospital, Zhengzhou,
3
Department of Radiology,
The Branch of Shanghai
Abstract:
In stroke, diagnosis and identification of the infarct core and the penumbra is integral to therapeutic determination.
With advances in magnetic resonance imaging (MRI) technology, stroke visualization has been radically altered.
MRI allows for better visualization of factors such as cerebral microbleeds (CMBs), lesion and penumbra size
and location, and thrombus identification; these factors help determine which treatments, ranging from tissue
plasminogen activator (tPA), anti-platelet therapy, or even surgery, are appropriate. Current stroke diagnosis
standards use several MRI modalities in conjunction, with T2- or T2*- weighted MRI to rule out intracerebral
hemorrhage (ICH), magnetic resonance angiography (MRA) for thrombus identification, and the diffusion-weighted
imaging (DWI) and perfusion-weighted imaging (PWI) mismatch for penumbral identification and therapeutic
determination. However, to better clarify the neurological environment, susceptibility-weighted imaging (SWI) for
assessing oxygen saturation and the presence of CMBs as well as additional modalities, such as amide proton
transfer (APT) imaging for pH mapping, have emerged to offer more insight into anatomical and biological conditions
during stroke. Further research has unveiled potential for alternative contrasts to gadolinium for PWI as well, as
the contrast has contraindications for patients with renal disease. Superparamagnetic iron oxide nanoparticles
(SPIONs) as an exogenous contrast and arterial spin labeling (ASL) as an endogenous contrast offer innovative
alternatives. Thus, emerging MRI modalities are enhancing the diagnostic capabilities of MRI in stroke and provide
more guidance for patient outcome by offering increased accessibility, accuracy, and information.
Key words:
Arterial spin labeling (ASL), cerebral microbleeds (CMBs), diffusion-weighted imaging (DWI), ischemic penumbra,
magnetic resonance angiography (MRA), perfusion-weighted imaging (PWI), superparamagnetic iron oxide
nanoparticles (SPIONs), susceptibility-weighted imaging (SWI)
Introduction of stroke and in determining whether tPA may
be prescribed. Recent advances have driven the

First Hospital, 9Department
of Physics, East China
Normal University,
Shanghai, 8Department of
Biomedical Engineering,
Northeast University,
Shenyang, China,
4
Department of Radiology,
The Catholic University
of Korea, St. Mary’s
Hospital, Seoul, Korea,
7
Department of Medical
Imaging, University
of Saskatchewan,
Saskatoon, Canada
Address for
correspondence:
Dr. Yuchuan Ding,
Department of Neurological
Surgery, School of Medicine,
Wayne State University,
550 E Canfield, Detroit,
Michigan - 48201, USA.
E-mail: yding@
med.wayne.edu
Submission: 26-05-2015
Accepted: 02-07-2015
S
troke is the fourth leading cause of death within
the United States (USA), with approximately
795,000 Americans suffering a stroke annually,
and it remains a leading cause of permanent
disability.[1] Stroke itself is characterized by a
disruption of cerebral blood flow (CBF) due to
either a thrombus/embolus blocking a vessel
or hemorrhage. Current treatments favor
thrombolytic therapy to dissolve clots using
tissue plasminogen activator (tPA). This should
generally be delivered within 3-4.5 hours from
the onset of stroke for optimally safe function.[2]
Outside this range, there is an increased risk of
intracerebral hemorrhage (ICH) with reduced
clinical benefits.[2] However, the use of this drug is
still very dependent on the diagnostic capabilities
of imaging. Computed tomography (CT) and
magnetic resonance imaging (MRI) are the key
modalities used in hospitals for the diagnosis
This is an open access article distributed under the terms of the
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which allows others to remix, tweak, and build upon the work non-
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For reprints contact: reprints@medknow.com
clinical use of MRI for the diagnosis of acute
ischemic stroke for its precision, its capability
for studying both anatomy and function, and
its accurate early detection of tissue disruption.
These characteristics of MRI provide a clear
clinical picture that then guides thrombolytic and
antiplatelet therapy. In light of this, the challenge
is to differentiate salvageable ischemic tissue
from tissue with irreversible loss, as well as those
patients at continued risk for ICH. In this paper,
the basic concepts of the various available MRI
sequences, as applied to stroke, will be reviewed.
MRI
Stroke visualization has been radically
altered with advances in MRI. MRI itself is a
revolutionary technology that allows for high-
resolution soft-tissue contrast within the body.
MRI uses the magnetic properties of hydrogen
How to cite this article: Rastogi R, Ding Y, Xia S,
Wang M, Luo Y, Choi HS, et al. Recent advances in
magnetic resonance imaging for stroke diagnosis.
Brain Circ 2015;1:26-37.

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Rastogi, et al.: MRI in stroke diagnosis
nuclei (protons in particular) found throughout the body to
generate a signal.[3] Generally, MRI utilizes a magnetic field to
align the hydrogen spins along the main field. Radiofrequency
(RF) pulses are then used to manipulate the spins to create
a measurable bulk transverse magnetization. Over time,
the signal decays in the transverse plane and regrows
longitudinally along the main field, each behavior having its
own characteristic time (T2 and T1, respectively).[3] Even with
just the early MRI methods, there were already four tissue
parameters to provide contrast: Spin density or the number of
spins per voxel, and the relaxation times T1, T2, and T2*. But
over the decades since its inception, MRI has developed so
that it can also be used to visualize and measure blood vessels
and blood flow, diffusion, perfusion, iron content, and oxygen
saturation, to name a few features.
Stroke
Stroke is a condition related to reduced blood flow and
perfusion caused by a thrombus/embolus or hemorrhage.
There are generally three territories associated with stroke:
The ischemic core (less than 12 mL/100 g/min), the penumbra
(12-20 mL/100 g/min), and oligemic tissue (greater than 20
mL/100 g/min); the first two are the most severely affected
by the reduced perfusion, the penumbra being less hypoxic/
ischemic. The ischemic tissue may not represent salvageable
tissue unless the flow is recovered within a few hours, while
the latter is associated more with secondary damage, being at
risk if the blood flow is not returned to normal. In the ischemic
region, the lack of oxygen supply reduces the availability
of high-energy phosphates such as adenosine triphosphate
(ATP) and elevates inorganic phosphates. Subsequent
dysfunction of the Na+/K+ channels results in an influx of
Na+ to cause osmotic disruption and cytotoxic edema.[4] On
the other hand, the penumbra still has marginal blood supply
from collateral sources and retains intact cellular metabolism.
Thus, it has the potential to be restored under reperfusion
conditions[5] and is vital in determining treatment options.
The oligemic tissue is less at risk than the penumbral tissue.
Ideally, it should also be possible to detect the size and age
of the stroke.
MRI in Stroke Diagnosis
Today, CT remains the mainstay in evaluating acute stroke,
although more and more sites are following CT with an MRI
scan within the first day. CT can rapidly assess the presence
of major intracranial hemorrhage and rule out giving tPA.
However, CT fails to register smaller cerebral microbleeds
(CMBs), an area that MRI is able to investigate very well,
especially with susceptibility-weighted imaging[6] (SWI). This
could have important consequences for follow-up treatment
with antiplatelet therapy.[7] There is much more to studying
stroke than just seeing the embolus. One wants to know the
changes in function and the hemodynamics of the tissue. This
is where the ability to study magnetic resonance angiography
(MRA), and perfusion and diffusion with MRI plays a key
role. CT can also perform perfusion-weighted imaging (PWI),
but still remains unable to compete with MRI when it comes
to studying CMBs and diffusion.[6,8,9] In fact, one of the critical
elements in determining what tissue may still be viable lies
in the concept of the diffusion/perfusion mismatch. There is
Brain Circulation - Vol 1, Issue 1, January 2015 27
evidence here that a larger perfusion abnormality relative to
a diffusion-weighted imaging (DWI) abnormality is a marker
of viable or penumbral tissue. This can affect the decision
for treatment, with the mismatch indicating a higher chance
of tissue recovery and perhaps extending the window of
treatment for the patient.[10-12]
DWI
DWI was first explored in stroke using an animal model in
the early 1990s.[4,13] These studies demonstrated that DWI
could detect ischemia within 45 min after onset of stroke,
while T2-weighted imaging failed to detect any ischemic
core even after 3 hours.[4] In DWI, the contrast is dependent
upon the apparent diffusion coefficient (ADC).[14] In ischemia,
diffusion is limited (restricted) due to cytotoxic edema that
occurs after stroke. With the Na+/K+ channel dysfunction and
influx of water, the cells swell (cytotoxic edema, restricted
diffusion, and lower ADC) and the volume of the extracellular
compartment is reduced (lower ADC) within the region of
infarct.[4,14] The reduction in ADC occurs within minutes and
can stay low for days, allowing for sensitive early detection
of ischemia. On the other hand, conventional MRI could take
6-8 hours to reveal any tissue changes, much past the ideal
period for thrombolytic treatment. In DWI, the ischemic core
appears hyperintense, while on the ADC maps, it is darker;
both of these effects are due to the decrease in diffusion.[14]
See Figure 1 parts d (DWI) and e (ADC) pretreatment; parts m
(DWI) and n (ADC) posttreatment. In certain animal studies,
DWI lesions have shown reversal of damage to the indicated
region.[15] However, this reversibility is often temporary and
abnormalities may reoccur up to a day later; however, the
benefits of early diagnosis outweigh the potential reversal.
[15]
Practically, DWI data are collected using a rapid scanning
technique, echo planar imaging (EPI), to avoid motion artifacts.
EPI uses a train of echoes to encode a two-dimensional (2D)
image rapidly and allows for whole-brain coverage in just
2-3 seconds.[16]
PWI
Dynamic susceptibility contrast perfusion (DSC PWI)
In DSC PWI, a bolus of an intravascular tracer, a contrast
agent, is usually injected into the antecubital vein. This contrast
agent, most commonly gadolinium diethylene triamine penta-
acetic acid (Gd-DTPA), travels to the brain and subsequently
washes out. During this process, T2*-weighted EPI data are
collected every few seconds for roughly 90 seconds and the
signal change is monitored over time to watch the effects of
this bolus. As the contrast agent perfuses through the brain,
the tissue experiences a signal drop due to the paramagnetic
susceptibility effects of the gadolinium. The image then
returns to normal as the contrast leaves the brain. Processing
these images through time can provide for cerebral blood
volume (CBV), CBF, mean transit time (MTT), and time to
peak (TTP) maps.[16] The ischemic region should show little
signal change over time, a decrease in CBV and an increase in
MTT. See Figure 1 parts f (CBF), g (CBV), h (MTT) and i (TTP)
pretreatment; parts o (CBF), p (CBV), q (MTT), and r (TTP)
posttreatment.
In comparing PWI and DWI, there have been cases of PWI
lesions identified without any results seen in DWI.[17] Such
cases, while rare, may cause confusion as to how to proceed
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Rastogi, et al.: MRI in stroke diagnosis

Figure 1: Two MRI scans from the same patient were acquired at different time points. The first and second rows are from the first scan in
the acute stage. The third and fourth rows are from the second MRI scan 1 week later. The images shown here were: (a) MRA (magnetic
resonance angiography), (b) T2-weighted, (c) SWI (susceptibility-weighted imaging), (d) DWI, (e) ADC, (f) rCBF (relative CBF), (g) rCBV
(relative CBV), (h) MTT and (i) TTP; for the second MRI scan one week later, the correlating images are (j) MRA, (k) T2-weighting, (l) SWI,
(m) DWI, (n) ADC, (o) rCBF, (p) rCBV, (q) MTT, and (r) TTP. Both DWI and ADC showed the stroke region in the first scan, but each returned
to normal in the second scan 1 week later. SWI showed much darker veins in the first scan and these disappeared in the second scan

with thrombolytic therapy, but Blondin et al.[17] determined in
a retrospective study that the lack of a DWI lesion does not
impact results of thrombolytic therapy and that sufficiently
depressed perfusion is enough indication for such treatment.
Our own experience suggests that several such cases may
arise each year in a given center, especially within a 3 hour
window when DWI may not show changes but PWI shows
clear changes. These patients would still be treated by tPA,
if possible. Therefore, PWI plays a key complementary role
to DWI.
Arterial spin labeling (ASL) perfusion
Although DSC PWI has been well adopted, there are
contraindications for the use of gadolinium in patients with

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Rastogi, et al.: MRI in stroke diagnosis

kidney disease and kidney failure, and using it today requires
glomerular filtration rate evaluation.[18] One contrast method
being explored as an alternative is ASL, where the inflow of
arterial blood that has been spatially labeled is used to both
visualize and quantify blood flow.[19] ASL has little dependence
on blood-brain barrier permeability changes, which is often
compromised in stroke patients and affects the signal from
exogenous contrast agents.[20] ASL has gained more momentum
recently at high fields because of the increased signal-to-noise
ratio (SNR), but it still requires several minutes and averaging
to create sufficient-quality data. More recent innovations in the
technique, such as background suppression, pseudocontinuous
ASL (pcASL), and a standardized approach to its use have
provided full brain coverage, improved SNR, and made it a
more reliable technique.[20-22] With these innovations, ASL is
capable of identifying regions of hypoperfusion consistent
with exogenous contrasts. It also more clearly images regions
of hyperperfusion, indicative of recanalization, compared to
exogenous contrast, but has a less clear identification of the
ischemic penumbra.[20] Overall, its ability to compete with
DSC PWI in stroke studies is still being investigated but is
increasingly promising.[22]
PWI and DWI mismatch
PWI and DWI both provide vital information regarding stroke
diagnostics. PWI can show perfusion changes throughout the
brain, while DWI shows local cytotoxic edema and hence the
damaged tissue or infarct core. The difference between these
two sets of images is referred to as the PWI/DWI mismatch see
Figure 1 PWI (parts h and i) shows a slightly larger perfusion
deficit than DWI (d) or ADC (e). Early studies suggested that
lesions with PWI-deficient regions (penumbra) larger than the
infarct core as seen with DWI could determine which tissue
was still salvageable.[10] The Diffusion and Perfusion Imaging
Evaluation For Understanding Stroke Evolution (DEFUSE)
study showed there were more favorable outcomes with early
recanalization compared to subjects who lacked the PWI/DWI
mismatch.[11] Furthermore, the mismatch allows clinicians
to select thrombolytic therapies in the 3-6 hour window, as
it indicates the presence of penumbra that will benefit from
reperfusion.[11,12]
The sensitivity of PWI to reduced perfusion, however, raises
another issue. It is able to accurately identify regions of very
mild hypoperfusion, regions that may still be receiving CBF
and thus are not in danger of damage. Thus, when using it to
identify the ischemic penumbra, certain regions may actually
be benign oligemia, leading to an overestimation of the damage
that will occur.[23] Continual refinements have been made to
define the parameters of the penumbra, evolving through
various studies such as DEFUSE and Echoplanar Imaging
Thrombolysis Evaluation Trial (EPITHET), in order to better
delineate the region from oligemia in PWI time-to-maximum
(Tmax) maps. Toth et al.[24] found that using larger Tmax values
(>4 seconds) and correcting PWI volumes with regard to the
arterial input function allows for a more accurate assessment
of the PWI volume. However, such corrections are not often
clinically employed, as many MRI systems have lacked those
capabilities until recently.[24] Thus, mismatch selection in
therapeutic determination is sensitive to PWI volume selection
methods.
An example of a severe PWI/DWI mismatch showing increases
in CBV but significant losses in oxygen saturation is given in
Figure 2. Here the brain tissue has successfully responded
to the challenge from stroke in an attempt to compensate
for the reduced perfusion. However, the opposite can also
happen, in that CBV and CBF reduce, and this may not be

Figure 2: An example of a PWI/DWI mismatch for an acute stroke patient. The images shown here were: (a) MRA; (b) T1; (c) SWI; (d) DWI;
(e) ADC; (f) rCBF; (g) rCBV; (h) MTT; (i) TTP. DWI and ADC showed several tiny regions of the stroke affected area, but the PWI MTT map
showed a much larger region with a perfusion abnormality. SWI showed much darker veins in the stroke region. MTT and TTP increased, and
meanwhile rCBV also increased while rCBF appears to be maintained at the normal level in the stroke region

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Rastogi, et al.: MRI in stroke diagnosis

Figure 3: A 70-year-old male with right limb weakness and unconsciousness 1.5 h after stroke. The images shown here were: (a) and (b)
T2WI; (c) and (d) DWI; (e) and (f) ADC; (g) and (h) TTP; (i) and (j) MTT; (k) and (l) CBV; (m) and (n) CBF. T2WI, DWI, and ADC were negative
(although there are subtle changes in DWI), but TTP and MTT showed obvious hypoperfusion in the bilateral cerebellar and left medial
occipital lobes. Both rCBF and rCBV were slightly decreased in the same area

a favorable prognostic factor for the patient. Such a case is
shown in Figure 3.
SWI
More recently, there have been a number of papers comparing
signal changes with SWI in stroke and their implications.[7,8,25-37]
In the presence of reduced flow, veins in SWI appear darker
than usual because of increased levels of deoxyhemoglobin
and are referred to as asymmetrically prominent cortical
veins (APCV).[37] The presence of these cortical veins will
usually match the MTT or TTP delays, and when treatment is
successful, they will disappear in parallel with the reduction
in MTT or TTP [see Figure  1 parts c (SWI), h (MTT), and i
(TTP) pretreatment; and parts l (SWI), q (MTT), and r (TTP)
posttreatment.] However, sometimes an increase in MTT is
seen but there is no concomitant increase in the visibility of the
veins. This PWI/SWI mismatch may be due to the presence
of collaterals and, therefore, be an indication that the tissue is
still viable with only limited effects from reduced perfusion
and normal levels of oxygen and, hence, is still treatable. (That
is, SWI may be useful in differentiating hypoperfusion from
delayed perfusion.)
SWI can also be used to detect CMBs. This may be important
for those receiving antiplatelet therapy. It has been shown
that those patients receiving antiplatelet therapy and having
CMBs fare much more poorly than those patients with CMBs
who are not on antiplatelet therapy. Further, the patients in
the latter cohort demonstrated better recovery and stayed in
the hospital for shorter periods of time.[7,31] It has also been
suggested that patients with three or more CMBs, as seen with
SWI, may also not fare well on antiplatelet therapy.[28] SWI has
also been shown to better detect hemorrhagic transformation
and CMBs than CT.[8]

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Rastogi, et al.: MRI in stroke diagnosis
a b
c by determining the responsible artery. That information then
Figure 4: An example of a double echo SWI evaluation of a stroke
patient with an occlusion of the right MCA and a thrombus within
the right MCA. (a) The short echo (TE = 7.5 ms) minimum intensity
projection (mIP) SWI data show the thrombus clearly with limited
signal from the veins; (b) The MRA shows the occlusion of the
right MCA; (c) The quantitative susceptibility map again shows the
thrombus clearly because of its high iron content while (d) the mIP
SWI shows both the thrombus and numerous veins. The veins on
the right side of the brain show the APCV effect indicating increased
levels of deoxyhemoglobin in the veins and reduced flow to the tissue.
Finally, the new multiecho SWI sequences[38] make it possible
not only to detect microbleeds but also to show the thrombus
clearly using short and long echo times [Figure 4]. SWI can often
find the thrombus, which cannot be seen with conventional
sequences, and this can help confirm which artery is responsible
for the stroke. It can also be used to determine if there is
thrombus resolution after tPA, which would provide a good
prognosis for the patient.[39,40] Finally, SWI may be useful in
conjunction with high-resolution MRA for recanalization via
microcatheter extraction of the thrombus when necessary.
Comparison between SWI and PWI
Four different scenarios have been seen when comparing
SWI and PWI. The first is that small lacunar acute infarction
was found in DWI, while both SWI and T2-weighted imaging
(T2WI) were normal. Although MTT was delayed, CBV and
CBF still remained normal, and in some cases even increased.
This phenomenon is called compensatory overperfusion after
acute ischemic stroke [Figure 1]. The second is that multiple
acute lacunar infarctions were found with DWI. Diffuse
hemisphere APCV were detected on SWI and the area covered
matched the delays seen in MTT and TTP. The CBF slightly
decreased, but CBV remained within the normal range [Figure
2]. This phenomenon is called compensatory normal perfusion
after acute ischemic stroke. The brain tissues pertaining to
the previous two scenarios should still be viable and are
likely to recover after treatment. The third is that a small
acute lacunar infarction was seen on DWI, but there were no
APCV, and the local delayed MTT and TTP combined with
decreased CBV and CBF [Figure 3]. This lacunar brain tissue
likely was compromised already and may well represent
nonfunctioning tissue. The fourth was the presence of a large
lobar hyperintensity on DWI, but no veins were seen with
SWI in the corresponding area along with a consistent region
of delayed MTT and TTP that matched a decreased CBV and
Brain Circulation - Vol 1, Issue 1, January 2015 31
CBF. This tissue has likely succumbed to prolonged hypoxic/
ischemic conditions and has become necrotic.
MRA
MRA has long been a mainstay for the study of neurovascular
diseases.[41] It can be acquired with or without contrast agents
and provides high-resolution information about the major
arteries in the brain. It is mainly used to look for stenosis and
lack of flow. More recent results show that resolutions as high as
0.25 mm × 0.25 mm × 0.5 mm are possible with a contrast agent
with superb small-vessel delineation.[39] Furthermore, with
newer rephasing/dephasing methods, even 0.5 mm isotropic
inplane resolution with 1 mm thick slices is possible without
a contrast agent in reasonable clinical times.[39] MRA makes
it possible to determine the source of the reduced perfusion
allows the physician to make a choice as to how to treat the
patient, whether with thrombolytic therapy, antiplatelet
therapy, or even intraarterial surgery. In conjunction with SWI
and PWI, the clinician can then paint a complete picture of the
status of the patient’s neurovascular system.[41,42]
Carotid vessel wall imaging
The carotid artery supplies the brain, eyes, and face with
oxygen-rich blood. However, this critical blood vessel is a
common site for atherosclerosis, a degenerative disease of the
arterial wall caused by the buildup of fatty substances and
cholesterol deposits.[43] The formation of atherosclerotic plaque
can cause progressive narrowing of the arterial lumen that may
eventually become severe enough to decrease or completely
block blood flow. Advanced plaques may break off and obstruct
blood flow, resulting in acute symptoms such as transient
ischemic attack (TIA) and cerebral thromboembolic stroke.[44,45]
The primary goal in treating carotid atherosclerotic disease is
to reduce the risk of stroke. Each year, approximately 800,000
Americans sustain a stroke and 20% of ischemic strokes are
associated with carotid atherosclerotic disease.[46,47] In addition
to medical therapy, approximately 124,000 costly carotid
revascularization procedures [89% carotid endarterectomy
(CEA) and 11% carotid artery stenting (CAS)] are conducted
each year in the USA to treat the disease and prevent stroke.[48]
Current management guidelines for carotid atherosclerotic
disease are primarily based on the degree of luminal stenosis
as determined by medical imaging, with high-grade (>70%)
stenosis as an indication for CEA or CAS. [49,50] However,
the degree of stenosis may not be an accurate indicator of
the severity of disease. The European Carotid Surgery Trial
reported that 43.8% of symptomatic patients had <30%
stenosis.[51] Conversely, some patients with high-grade stenosis
never develop symptoms but are likely over treated.[52] Hence,
an accurate, reliable approach to risk stratification of carotid
atherosclerotic lesions is highly desired for guiding treatment
decisions.
Pathology studies revealed that atherosclerotic plaque
destabilization followed by acute thromboembolic events is
related to specific plaque characteristics, namely the presence
of a large lipid-rich necrotic core (LRNC) with an overlying
thin/ruptured fibrous cap (FC), intraplaque hemorrhage (IPH),
and calcification (CA).[53,54] Characterization of such vulnerable
plaque features may help better identify high-risk lesions.[43,55]
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Rastogi, et al.: MRI in stroke diagnosis

In this regard, MRI has shown unique strengths over other
commonly used diagnostic imaging modalities (i.e., x-ray
angiography, duplex ultrasound, and CT) that merely provide
information on luminal stenosis. Extensive research efforts
have been devoted to the development of MRI techniques for
carotid plaque characterization over the last two decades. Early
interests were focused on lumen imaging (i.e., MRA) and wall
morphological imaging (i.e., black-blood vessel wall imaging as
shown in Figure 5a), both of which provide useful information
on the presence of artery stenoses or atherosclerotic plaques
as well as their distribution. However, plaque compositional
imaging with MR is increasingly becoming more popular
in the research community. The conventional MR approach
identifies different plaque components based on their signal
patterns on multicontrast-weighted images acquired typically
with T1-, T2-, and proton density-weighted fast spin-echo
(FSE), and time-of-flight (TOF) [Figure 5b-e].[43,55] Using the
protocol given above, high sensitivity and specificity for
detecting various plaque components have been achieved.[56] To
enhance the sensitivity and confidence for some specific plaque
constituents, additional contrast weightings may be included.
Delayed contrast-enhanced imaging creates sharp contrast
between LRNC and FC, allowing for the identification of LRNC.
[57,58]
Furthermore, it has been shown to significantly overcome
the low reproducibility in characterizing FC status associated
with the noncontrast-enhanced protocol.[59] Recently, a heavily
T1-weighted sequence, namely magnetization-prepared rapid
acquisition with gradient echo (MP-RAGE),[60] was proved to
be more sensitive to IPH than conventional T1-weighted FSE
or TOF.[61] In addition, several novel techniques have been
developed in an attempt to offer multiple capabilities with a
single scan. For example, three-dimensional (3D) simultaneous
noncontrast angiography and intraplaque hemorrhage
(SNAP) imaging provides both noncontrast-enhanced MRA
and IPH detection;[62] 3D spoiled gradient recalled echo pulse
sequence for hemorrhage assessment using inversion recovery
and multiple echoes (SHINE) characterizes the age of IPH
in addition to IPH detection;[63] and finally, multicontrast
atherosclerosis characterization (MATCH) imaging is capable
of detection of multiple plaque constituents with a single
scan.[64]
As for carotid atherosclerosis MRI, black-blood techniques
are the method of choice extensively utilized for vessel wall
morphological imaging and plaque compositional imaging.
[43]
To make the vessel wall more conspicuous, luminal blood
signals need to be suppressed. This is typically achieved by
exploiting some flow properties such as in/outflow or fast
flow velocity. However, blood suppression is often incomplete,
particularly at locations involving complex flow.[65] As a result,
residual juxtaluminal blood signals may be mistaken as part
of carotid artery wall, thus leading to the overestimation of
wall area or plaque burden. SWI may be a new approach to
investigate the presence of hemorrhage or of calcium, which
may not be seen if on the interior of the vessel wall and which
are also important to recognize in the wall itself.[66] Today, it is
possible to image the vessel wall with SWI to obtain full region
of interest (ROI) coverage in three-dimension without the need
to suppress the signal from the blood. Exquisite contrast on
the SWI images should allow clear delineation between IPH
and CA in plaques.
Intracranial vessel wall imaging
Atherosclerosis of the intracranial artery is also an important
cause of stroke over and above the extracranial artery
atherosclerosis.[67,68] Compared with extracranial atherosclerosis,
intracranial artery atherosclerosis is more frequent in the Asian
population than the Western population.[69-71] Previously,
luminal stenosis of intracranial artery had been considered
as a risk factor of stroke.[72] However, luminography cannot
reveal the in situ pathology occurring at the arterial wall.
Pathologically, intracranial arteries are different in terms
of tight endothelial junction (blood-brain barrier), lack
of vasa vasorum, and thin elastic lamina, compared with
extracranial arteries.[73] However, vulnerable intracranial
artery atherosclerosis shares with carotid artery atherosclerosis
some common features such as presence of IPH, large LRNC,
inflammation, and thin FC. Therefore, recent studies have

Figure 5: Representative carotid artery wall images acquired using 3D and 2D vessel wall imaging techniques from a symptomatic 43-year-old
male patient. (a) 3D isotropic 0.78-mm images acquired with a 3D FSE sequence can be reformatted into a long axis view to better delineate
the atherosclerotic lesions at the carotid bifurcation; (b.1-e.1) location-matched multicontrast images (0.63 × 0.63 × 2.0 mm3) acquired with
TOF, pre-contrast T1- and T2-weighted FSE, and post-contrast T1-weighted FSE depict a plaque with large LRNC (arrows) and calcification
(arrowheads) at the carotid bifurcation (orange arrows in a.); (b.2-e.2) location-matched multicontrast images acquired with the same 2D
imaging protocol depict normal vessel wall at the common carotid artery (blue arrows in a.)

32 Brain Circulation - Vol 1, Issue 1, January 2015

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Rastogi, et al.: MRI in stroke diagnosis
Figure 6: A 26-year-old male who suffered from transient weakness of
the left limbs 8 days before being imaged. The T2WI was negative.
The digital subtraction angiography (DSA) showed stenosis of the
right MCA. The high-resolution MRI showed eccentric plaque of the
MCA wall with vivid enhancement postcontrast
focused on visualizing the in situ arterial wall using high-
resolution multicontrast MRI.[74-78] Contrast enhancement at
the intracranial arterial wall is considered pathologic and is
correlated with inflammation[79] [Figure 6]. Several studies
have suggested that enhancement of the intracranial arterial
wall is a marker of histologically active disease and a potential
marker for the culprit atherosclerotic lesion of the intracranial
artery. It is still challenging to visualize the wall of intracranial
arteries even using high field MRI because the thickness of the
intracranial arterial wall is smaller than that of extracranial
arteries. Further research should be performed to achieve
suitable SNR, contrast-to-noise ratio, and methods of analysis
on intracranial artery atherosclerosis.
The current medical management of intracranial artery
atherosclerosis consists of antiplatelets, anticoagulants,
and statins.[80-82] Endovascular and surgical treatments are
alternative treatment options in patients without response
to best medical therapy.[83] However, in the previous studies
on proper management of intracranial artery atherosclerosis,
eligible patients were selected by means of luminography and
clinical symptoms. Further clinical research is still needed to
evaluate subclinical patients at risk for future stroke.
Amide proton transfer (APT) imaging and pH mapping
The ability to map the pH in the brain could allow direct
measurements of physiological changes in stroke. This is
through a chemical exchange saturation transfer technique
called APT imaging, or pH-weighted MRI. More thoroughly
explored in animal studies, APT has only recently been tested
on human subjects in the more preliminary condition. In APT
imaging, an RF pulse is used to label the water-exchangeable
amide protons on endogenous mobile and tissue proteins.[23]
These labeled protons are then tracked for contrast, with proton
exchange rates with water indicative of pH; slow rates with
lowered pH are due to increased proton concentrations.
Thus, in stroke, the stroke volume appears as a hypointense
region.[23,84] In rat models, the additional use of pH-MRI has
allowed for the distinction between the benign oligemia and
the penumbra, a distinction that was difficult to make with
Brain Circulation - Vol 1, Issue 1, January 2015 33
the PWI/DWI mismatch alone.[23] The region of lower pH
was larger than DWI lesions but smaller than PWI lesions,
allowing for a more accurate representation of the penumbra
and potentially allowing for better prediction of outcome in
terms of lesion growth during ischemia.[23]
Furthermore, after stroke, the lack of oxygen forces cells to turn
to glycolysis for energy, which creates an excess of lactate. In
such regions, the accumulation of lactate creates tissue acidosis,
damaging the tissue and disrupting normal metabolism even
when oxygen is returned. APT imaging correlates well with
the lactic acidosis occurring post infarct within the brain, with
further studies by Sun et al.[85] demonstrating pH correlation
with lactate content. Harston et al.[86] performed proof-of-
concept studies on human stroke subjects, showing that APT
imaging provides a more accurate assessment and delineation
of the ischemic penumbra and indicating which tissue will
lead to infarction. APT imaging can be done within 3 minutes,
ensuring that this could become a practical diagnostic tool.[86]
An example image using this approach is shown in Figure 7.
Novel Contrast Agents
Other exogenous contrast agents have emerged for potential
use with T2*-weighted MRI imaging as alternatives to current
gadolinium (Gd)-based contrasts. One such method is the use
of PEGylated superparamagnetic iron oxide nanoparticles
(SPIONs) to identify specifically the leakage of the blood-brain
barrier in stroke. Liu et al.[87] have explored this application
within mice models. Because of their superparamagnetic
properties, much smaller amounts of contrast are necessary for
distinct contrast in imaging. SPIONs are injected and traced;
they aggregate in areas where the blood-brain barrier is leaky,
such as compromised ischemic tissue, creating a hypointense
signal in the area due to their disruptive susceptibility effects.
The nanoparticle had equivalent results when compared to
Gd-DTPA in these models and allows for the unique capability
of the compromised blood-brain barrier to be dynamically
monitored for a 24 hour period after injection.[87] The long life
of the contrast offers the potential for tracking tissue behavior
after therapeutic intervention as well. Given the concern today
about nephrogenic systemic fibrosis (NSF),[18] these iron-based
agents may provide an alternative contrast agent for patients
with compromised kidney function.[87]
An Integrated MRI Stroke Protocol
Current clinical usage favors the multimodal use of MRI.[42]
This entails taking T2- or T2*-weighted imaging, and DWI
and PWI imaging. The T2*-weighted imaging allows for
accurate rule out or definition of ischemic hemorrhage, due
to its susceptibility-weighted images. Meanwhile, the other
modalities are used together. DWI and PWI mismatch are
the most modern clinical applications of MRI in stroke. The
presence of a mismatch (PWI > DWI) indicates the presence
of a penumbra, which is currently utilized as an indication
for thrombolytic therapy in the clinical arena. The mismatch,
when accompanied by confirmed vessel occlusion in the middle
cerebral artery (MCA), is a definite indication for recanalization
and thrombolytic therapy.[88] Cases with a PWI/DWI match
or a DWI lesion without hypoperfusion are less certain. In the
former, it is difficult to determine if there is still salvageable
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Rastogi, et al.: MRI in stroke diagnosis
Figure 7: Acute infarct in the corpus callosum. The infarct shows hypointensity on T1WI (a); hyperintensity on T2WI (b); hyperintensity on DWI
(c); and hypointensity on the phase map using a length and offset varied saturation (LOVARS) scheme
tissue. In the latter, therapy is not needed, as it is indicative
of spontaneous recanalization.[89] This may not be the case,
however, if the time of arrival to the hospital is within a 3 hour
time window (what might be called the superacute stage), and
the patient may still require treatment. This is often the case
when there is a stroke lesion in the medulla, brainstem, or basal
ganglia with a mismatch.
Furthermore, using both PWI and DWI allows for accurate
stroke identification in cases where there is a false negative
DWI or no DWI lesion present.[17] All these features are well
demonstrated by the data in Figure 1.
Finally, the use of SWI will allow for the detection of
microbleeds to assess the role of anti-platelet therapy and
changes in oxygen saturation in the local venous structures.
Both of these may have future treatment consequences, the
former for determining if there are too many microbleeds for
anti-platelet therapy and the latter in assessing the SWI/PWI
mismatch and extending the window of treatment beyond the
usual 4.5 to 6 hour window.
One of the advantages of multimodal MRI is the amount of
information it offers within a limited amount of time, with
complete examinations across DWI, PWI, T2*-weighted
(preferably SWI), and conventional imaging completed within
10 minutes.[16] The immediacy and speed of such diverse
imaging modalities make multimodal MRI very attractive in
emergency situations such as acute stroke and allows for more
immediate decision making, a vital point in stroke where “time
is brain.”[88]
Conclusion
Overall, noninvasive, nonionizing imaging methods such
as MRI offer the potential to follow patients longitudinally
and ascertain, perhaps, why some patients recover better
than others and how the brain responds to treatment. Some
questions that might be answered include: “Does perfusion
recover immediately for all patients who do well or can a
slow recovery of perfusion also be indicative of recovery for
patients?”; “Should patients with CMBs be given antiplatelet
therapy?”; “Does an SWI/MTT mismatch indicate collateral
perfusion and hence suggest that the tissue is still viable?”
34 Brain Circulation - Vol 1, Issue 1, January 2015
More specifically, MRI is invaluable in its diagnostic capability
for ischemia, in terms of stroke identification, prognostic
capabilities, and therapeutic indications. Current standards
involve the use of multiple sequences including T2-weighted,
T2*-weighted, DWI, and PWI for stroke identification
and therapeutic determination. Today, MRI is the key in
determining who will do poorly if no intervention is employed.
Emerging contrast mechanisms, such as SWI for monitoring
oxygen saturation and detecting CMBs and APT for assessing
tissue function, are increasing the information and predictive
power that MRI can provide.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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