Imaging of Acute Stroke

Vaishali Choksi, MD, Douglas J. Quint, MD, Pia Maly-Sundgren, MD, Ellen Hoeffner, MD
Appl Radiol. 2005;34(2):10-19

In patients with acute onset of stroke-like symptoms, imaging can rule out nonvascular causes of
the symptoms, define the extent of an acute ischemic process, differentiate between the infarcted
core and the ischemic penumbra of an area of acute ischemic change, possibly identify the cause
of an acute ischemic process, and identify which patients might benefit from thrombolytic
therapy. The authors review the use of computed tomography (CT), magnetic resonance (MR)
imaging, diffusion/perfusion MR, perfusion CT, and CT angiography in the setting of acute
stroke.
Symptomatic cerebral infarction ("stroke") affects more than 750,000 Americans each year and
has a mortality of 22%.[1] It is the third leading cause of death in the United States and the annual
costs are estimated to be $45 billion.[1] Until the mid 1990s, management of stroke patients
usually involved supportive care in the acute period, followed by a diagnostic workup in an
attempt to define a cause of the patient's symptoms for which treatment might be instituted with
the goal of preventing future events. For example, computed tomography (CT) was performed to
rule out other pathologic processes that can present with stroke-like symptoms, such as
neoplasms, acute extra-axial fluid collections (epidural hematomas, subdural hematomas),
infections, or any cause of a seizure (masses, vascular malformation). CT was also performed to
rule out hemorrhage associated with an area of cerebral infarction that would contraindicate
anticoagulation therapy. Later, diagnostic workup including cerebral angiography was often
performed to identify arterial abnormalities that might be amenable to surgical (eg,
endarterectomy) or medical (eg, anti-platelet, anticoagulation) therapy.
In 1995, the National Institute of Neurologic Disorders Study (NINDS) Group [2] reported that the
use of intravenous (IV) recombinant tissue plasminogen activator (t-PA), if administered to
patients with ischemic stroke within 3 hours of symptom onset, resulted in an absolute improved

outcome (end point: little or no disability 3 months after the event). This work has been
confirmed by subsequent studies. The U.S. Food and Drug Administration (FDA) approved the
use of IV t-PA for this purpose in 1996. The use of thrombolytic therapy for intra-arterial
treatment of anterior circulation thrombi has been shown to be efficacious up to 6 hours after
symptom onset[3,4]; but as of the end of 2004, the FDA had not yet approved its use for this
purpose.
Early imaging has become crucial in the management of these patients. Specifically, acute
intracranial hemorrhage and nonvascular causes of stroke symptoms need to be ruled out within
3 hours of symptom onset so that the use of IV t-PA can be considered. As t-PA is not a benign
drug (it is associated with a 10-fold increased risk of causing an intracranial hemorrhage),
imaging has become an important tool for identifying which patients may benefit from
thrombolytic therapy and which patients may not and, therefore, should not be exposed to the
risks of such treatment. Imaging also provides information that could potentially identify
subgroups of patients who might benefit most from aggressive therapy beyond the accepted
"therapeutic window" of 3 hours. Therefore, it is important for interpreters of imaging studies to
be aware of specifically what to search for and report upon on emergent scans.
CT remains the predominant imaging modality for initial evaluation of patients with suspected
stroke. Lesions that clinically can mimic ischemic stroke, such as hemorrhages, tumors,
infections, vascular malformations, etc., can be excluded. Most CT scans are negative with
respect to early signs of an acute ischemic process in the first 6 hours after symptom onset
(which, as mentioned above, is the current "therapeutic window" during which pharmacologic
intervention can affect patient outcome). However, several subtle parenchymal findings
reflecting underlying cytotoxic edema (an early pathophysiologic finding in ischemia) can
sometimes be seen and should be searched for. Such signs include "blurring" of the gray matterwhite matter junction due to decreased attenuation of the gray matter as manifested by the
"insular ribbon" sign (loss of the usual slightly increased attenuation of the insular cortex just
superficial to the external/extreme capsules [Figure 1]) or "obscuration" of the lentiform nucleus
(loss of the normal attenuation difference of the globus pallidus and/or putamen with respect to
contiguous white matter structures [Figure 2]). In patients with middle cerebral artery (MCA)
territory ischemia, local mass effect in the form of effacement of sulci or narrowing of the

sylvian fissure may also be identified. These parenchymal changes, when seen in the first 3 hours
after onset of stroke symptoms, appear to correlate with stroke severity.[5]

(Enlarge Image)
Insular ribbon sign of acute stroke on CT. In a 70-year-old man with acute right-sided weakness,
emergent CT reveals loss of the left insular ribbon (solid arrows), consistent with cytotoxic
edema, as compared with the normal-appearing right insular ribbon (open arrows). Follow-up CT
(not shown) showed a large left middle cerebral artery infarction.

(Enlarge Image)
Obscuration of the lentiform nucleus sign of acute stroke on CT. A 9-year-old child 5 hours after
a traumatic bicycle accident with deteriorating mental status. (A) Emergent CT reveals loss of
normal left lentiform nuclear attenuation (solid arrows) consistent with cytotoxic edema, as
compared with the normal-appearing right lentiform nuclei (open arrows). (B) Follow-up CT
confirms a left basal ganglia infarction.

(Enlarge Image)
Obscuration of the lentiform nucleus sign of acute stroke on CT. A 9-year-old child 5 hours after
a traumatic bicycle accident with deteriorating mental status. (A) Emergent CT reveals loss of
normal left lentiform nuclear attenuation (solid arrows) consistent with cytotoxic edema, as

compared with the normal-appearing right lentiform nuclei (open arrows). (B) Follow-up CT
confirms a left basal ganglia infarction.
An extraparenchymal CT finding that can be identified as early as 90 minutes [6,7] after symptom
onset is the "hyperdense vessel sign" (Figure 3), which is usually seen in the proximal (M1
segment) MCA, but can be seen in any arterial structure.[8,9] The increased density in the vessel is
thought to be secondary to local slow intravascular blood flow due to an intra-arterial thrombus
or may represent direct visualization of the thrombus itself.[6,8]

(Enlarge Image)
Hyperdense middle cerebral artery (MCA) sign of acute thrombus formation. A 55-year-old
woman with a 90-minute history of left hemiplegia and left facial droop. Head CT shows high
attenuation within the expected location of the right MCA (arrows), which is consistent with an
acute thrombus.
While the NINDS study[2] established that IV t-PA was useful if given to patients with
nonhemorrhagic stroke within 3 hours of symptom onset regardless of associated parenchymal
ischemic changes, the European Cooperative Acute Stroke Study (ECASS) trial [10] studied
patients with stroke symptoms of <6 hours' duration who had CT-demonstrable ischemic changes
involving no more than one third of the MCA territory. This and subsequent studies revealed that
although patients with CT-demonstrable parenchymal changes within the first 3 hours after
symptom onset have a relatively worse outcome than patients who present with symptoms but no
abnormalities on CT,[5] they may still benefit from IV t-PA administration if the identified
parenchymal changes involve less than one third of a vascular territory.
Therefore, when reporting a CT scan for this patient population, pertinent findings to be
mentioned include: the presence or absence of hemorrhage, the presence and extent of any
ischemic parenchymal changes, and the presence or absence of nonvascular etiologies of strokelike symptoms

Conventional (standard spin-echo) magnetic resonance imaging (MRI) shows essentially the
same parenchymal changes that can be seen on CT scanning, but with a greater degree of
sensitivity and specificity.[8] Cytotoxic edema of gray matter is seen as increased T2 signal and,
in the case of MCA ischemia, is often first identified in the region of the insular cortex (ie, the
MR corollary of the "insular ribbon" sign on a CT scan) or involving the lentiform nuclei of the
basal ganglia (ie, the MR corollary of "obscuration" of the lentiform nucleus on a CT scan).
Similarly, mild mass effect associated with early ischemic change is usually easier to identify on
MRI. The greater contrast resolution of MR permits the earlier and more confident delineation of
these findings, though these changes are still usually not seen for 3 to 4 hours. Exaggerated
intravascular contrast enhancement reflecting relative stasis of contrast material within blood
vessels in the involved ischemic territory is an MR sign of an acute vascular occlusion. [8] While
this sign can be seen within minutes of an occlusion, as it can persist for up to a week and does
not identify the specific blood vessel involved, it is therefore relatively nonspecific for
identifying a hyperacute area of ischemic change. Diffusion-weighted MRI ( d MR) is based on
the principle that random Brownian motion of water molecules in tissues can be measured and
quantified. Water molecules that are not "restricted" by cell membranes, macromolecules, or
other structures will have greater net diffusion over a given period of time than will water
molecules surrounded by cell organelles, membranes, large proteins, etc. Therefore, water
molecules in the lateral ventricles have "high" (a large amount of) diffusion while water
molecules within a cell have more "limited" diffusion.
During an acute ischemic event, cellular adenosine triphosphate (ATP) is depleted, leading to
failure of cell membrane sodium-potassium pumps. This (along with other chemical effects)
leads to an acute influx of water into cells with swelling of the affected cells (cytotoxic edema).
The end result is that the increased intracellular water (which shows less overall diffusion than
does extracellular interstitial water) demonstrates a decrease in the amount of net diffusion of
water present in brain parenchyma experiencing cytotoxic edema. (It should be noted that there
are alternative explanations for what is occurring at the cellular level, but the end result is the
same with respect to imaging.)
The net diffusion of water for any given tissue can be measured and displayed on a d MR scan
(Figure 4A). Areas of decreased water diffusion will be seen as areas of increased signal on d

MR and can be seen as early as 22 minutes after an ischemic insult. [11] As d MR findings can
occasionally be mimicked by chronic T2-changes (so-called "T2 shine-through"), apparent
diffusion coefficient (ADC) maps (Figure 4B) can be generated. [12,13] that reflect only diffusion
data. Changes on d MR scans or ADC maps are usually considered evidence of irreversible
ischemic damage, though there are reports of reversal of d MR findings after successful
recanalization of a blood vessel with intra-arterial thrombolysis.[14] Similarly, although d MR is
considered a sensitive method for ruling out infarction, there have also been case reports of
patients with initially (within 4 hours) negative d MR scans who went on to cerebral infarction.
[15]

(Enlarge Image)
Acute cerebral infarction on diffusion MR and apparent diffusion coefficient (ADC) maps. A 5year-old boywith idiopathic thrombotic purpura and acute fulminant hepatic failure with acute
mental status decline. (A) T2-weighted MRI shows left frontoparietal predominantly cortical
areas of abnormal increasing T2 signal (arrows) and several focal deep white-matter areas of
abnormal T2 signal. (B) Diffusion MRI reveals more extensive ischemic changes in the left
frontoparietal region involving both gray and white matter (arrows). (C) Low signal (arrows) on
the ADC map confirms the acute nature of the diffusion changes. Cerebral infarction was
identified in this region at autopsy.

(Enlarge Image)
Acute cerebral infarction on diffusion MR and apparent diffusion coefficient (ADC) maps. A 5year-old boywith idiopathic thrombotic purpura and acute fulminant hepatic failure with acute
mental status decline. (A) T2-weighted MRI shows left frontoparietal predominantly cortical
areas of abnormal increasing T2 signal (arrows) and several focal deep white-matter areas of

abnormal T2 signal. (B) Diffusion MRI reveals more extensive ischemic changes in the left
frontoparietal region involving both gray and white matter (arrows). (C) Low signal (arrows) on
the ADC map confirms the acute nature of the diffusion changes. Cerebral infarction was
identified in this region at autopsy.

(Enlarge Image)
Acute cerebral infarction on diffusion MR and apparent diffusion coefficient (ADC) maps. A 5year-old boywith idiopathic thrombotic purpura and acute fulminant hepatic failure with acute
mental status decline. (A) T2-weighted MRI shows left frontoparietal predominantly cortical
areas of abnormal increasing T2 signal (arrows) and several focal deep white-matter areas of
abnormal T2 signal. (B) Diffusion MRI reveals more extensive ischemic changes in the left
frontoparietal region involving both gray and white matter (arrows). (C) Low signal (arrows) on
the ADC map confirms the acute nature of the diffusion changes. Cerebral infarction was
identified in this region at autopsy.
MRI is considered a better test than CT for identifying acute ischemic changes, with d MR being
a highly specific test for early detection of usually irreversible parenchymal injury.
Perfusion imaging, be it perfusion MR ( p MR) or perfusion CT ( p CT), evaluates the
characteristics of blood flow to a given region of the brain. It is recognized that brain
parenchyma can be hypoperfused without permanent parenchymal injury. Therefore, a brain
region with lower than normal perfusion can either be infarcted or be at increased risk to
progress to infarction. The concept of "ischemic penumbra" refers to an area of reduced brain
parenchymal perfusion with or without associated loss of neuronal function, but with involved
neurons remaining viable.[16] This area of the brain is considered "at risk" to go on to irreversible
infarction if blood flow is not improved. This area of brain usually separates an area of frank
cerebral infarction (presumably irreversible injury) from normal brain. It is this area of the brain
that aggressive IV thrombolytic or neurointerventional management targets to protect from
further injury. The time period during which brain tissue within the ischemic penumbra remains

viable is debated,[17] as the transition of brain tissue from potentially reversible to irreversible
injury is dependent on the severity and duration of the underlying ischemic process. [16] As a
patient with a significant penumbra territory is likely to benefit from thrombolytic therapy, one
of the current goals of imaging is to try to identify this "at risk" brain tissue so that appropriate
aggressive therapy can be targeted to this region. Similarly, if imaging can indicate that there is
little or no penumbral territory, those patients should probably not be exposed to the risks of
aggressive therapy, because there may be little viable brain to salvage.
Perfusion MR imaging can be performed by multiple different techniques, However, a contrastenhanced dynamic susceptibility (T2*-weighted) bolus technique is most commonly used.
Hemodynamic maps are generated based on the degree of signal-intensity decrease identified on
rapidly acquired scans obtained as a bolus of IV contrast material passes through the brain.
Various hemodynamic parameters such as relative cerebral blood flow (CBF; in mL/min),
relative cerebral blood volume (CBV; in mL), mean transit time (MTT; in sec), bolus arrival time
(in sec) and flow heterogeneity[18] can be measured and/or calculated (Figure 5). Uninvolved
contralateral brain tissue is presumed to be "normal," and ratios of abnormal/normal can be
determined. The exact role of each perfusion parameter in the evaluation of patients for
determining the ischemic core (area of irreversible infarction), ischemic penumbra (area of
hypoperfusion, but still potentially salvageable brain) and the final infarction size remains
controversial.[14,17,19]

(Enlarge Image)
Diffusion-perfusion MR mismatch. A 57-year-old woman with hypertension who presented with
left-sided weakness and gaze palsy.

(Enlarge Image)

Diffusion-perfusion MR mismatch. A 57-year-old woman with hypertension who presented with

left-sided weakness and gaze palsy.

(Enlarge Image)
Diffusion-perfusion MR mismatch. A 57-year-old woman with hypertension who presented with
left-sided weakness and gaze palsy.
If an area of MR perfusion abnormality (that theoretically can include areas of salvageable brain)
is larger than the underlying area of MR diffusion abnormality (which presumably represents
irreversibly damaged brain tissue -- the ischemic core) (Figure 5), then the difference in the
amount of affected brain between these 2 studies may represent an area of potentially
salvageable brain, the ischemic penumbra. The identification or exclusion of such an MR
diffusion-perfusion mismatch may be the key for determining which patients might maximally
benefit from aggressive (eg, thrombolytic or interventional) therapy.[23]
Perfusion CT is performed in a manner similar to p MR. Serial CT scans are acquired rapidly to
dynamically track a bolus of IV contrast material as it travels through the brain [24] at a single
location (ie, the basal ganglia region in the case of suspected MCA stroke) or at several
contiguous locations (but covering no more than a 2-cm-thick slab of the brain). Again,
hemodynamic maps of brain perfusion can be generated as this contrast bolus passes through the
brain. Different parameters, including time-to-peak (TTP; the time that elapses between the start
of an IV contrast injection and the maximal attenuation of contrast-enhanced blood as it passes
through a defined region of the brain), MTT (which can be oversimplified to be considered the
time it takes blood to flow from a major cerebral artery feeding a given region of the brain to the
major cerebral vein draining that region), CBV (the volume of blood in a defined portion of the
brain at any given time), and CBF (cerebral blood volume/min) can be measured or calculated.
While there is debate about the significance and reliability of these parameters, some
researchers[24,25] believe that CBF (or MTT) on p CT is similar to a perfusion abnormality on p
MR, while CBV on p CT is similar to a diffusion abnormality on p MR, so that a CBF/CBV (or

MTT/CBV) "mismatch" on perfusion CT (Figure 6) is similar to a perfusion/diffusion

"mismatch" on MR (Figure 5) and may have the same implications with respect to identifying
the presence or absence of an ischemic penumbra and the potential usefulness of aggressive
neurointerventional therapy in any given patient.

(Enlarge Image)
Perfusion CT mismatch. Imaging of a 76-year-old woman who had been found unresponsive
with a right facial droop. (A) Screening head CT is suggestive of left middle cerebral artery
ischemic process as manifested by mild sulcal effacement (large solid arrows) and a subtle
insular ribbon sign (small, solid arrows). (B) Perfusion CT performed immediately after the
screening head CT reveals decreased cerebral blood volume (CBV) in the left frontal lobe region
(white arrows), which is suggestive of irreversible ischemic change. The CBV in the left
temporal lobe is normal and symmetric with the right temporal lobe. (C) Mean transit time
(MTT) perfusion CT shows increased transit time in the left temporal region (straight white
arrows) relative to the right temporal region (curved white arrows), which is consistent with a
perfusion deficit. This "mismatch" between the MTT (C) and the CBV (B) perfusion scans (ie,
the normal CBV with an increased MTT) suggests the presence of possibly salvageable brain
tissue in the left temporal region at that time.

(Enlarge Image)
Perfusion CT mismatch. Imaging of a 76-year-old woman who had been found unresponsive
with a right facial droop. (A) Screening head CT is suggestive of left middle cerebral artery
ischemic process as manifested by mild sulcal effacement (large solid arrows) and a subtle
insular ribbon sign (small, solid arrows). (B) Perfusion CT performed immediately after the
screening head CT reveals decreased cerebral blood volume (CBV) in the left frontal lobe region

(white arrows), which is suggestive of irreversible ischemic change. The CBV in the left
temporal lobe is normal and symmetric with the right temporal lobe. (C) Mean transit time
(MTT) perfusion CT shows increased transit time in the left temporal region (straight white
arrows) relative to the right temporal region (curved white arrows), which is consistent with a
perfusion deficit. This "mismatch" between the MTT (C) and the CBV (B) perfusion scans (ie,
the normal CBV with an increased MTT) suggests the presence of possibly salvageable brain
tissue in the left temporal region at that time.

(Enlarge Image)
Perfusion CT mismatch. Imaging of a 76-year-old woman who had been found unresponsive
with a right facial droop. (A) Screening head CT is suggestive of left middle cerebral artery
ischemic process as manifested by mild sulcal effacement (large solid arrows) and a subtle
insular ribbon sign (small, solid arrows). (B) Perfusion CT performed immediately after the
screening head CT reveals decreased cerebral blood volume (CBV) in the left frontal lobe region
(white arrows), which is suggestive of irreversible ischemic change. The CBV in the left
temporal lobe is normal and symmetric with the right temporal lobe. (C) Mean transit time
(MTT) perfusion CT shows increased transit time in the left temporal region (straight white
arrows) relative to the right temporal region (curved white arrows), which is consistent with a
perfusion deficit. This "mismatch" between the MTT (C) and the CBV (B) perfusion scans (ie,
the normal CBV with an increased MTT) suggests the presence of possibly salvageable brain
tissue in the left temporal region at that time.

(Enlarge Image)
Perfusion CT mismatch. Imaging of a 76-year-old woman who had been found unresponsive
with a right facial droop. (A) Screening head CT is suggestive of left middle cerebral artery

ischemic process as manifested by mild sulcal effacement (large solid arrows) and a subtle
insular ribbon sign (small, solid arrows). (B) Perfusion CT performed immediately after the
screening head CT reveals decreased cerebral blood volume (CBV) in the left frontal lobe region
(white arrows), which is suggestive of irreversible ischemic change. The CBV in the left
temporal lobe is normal and symmetric with the right temporal lobe. (C) Mean transit time
(MTT) perfusion CT shows increased transit time in the left temporal region (straight white
arrows) relative to the right temporal region (curved white arrows), which is consistent with a
perfusion deficit. This "mismatch" between the MTT (C) and the CBV (B) perfusion scans (ie,
the normal CBV with an increased MTT) suggests the presence of possibly salvageable brain
tissue in the left temporal region at that time.