ADVANCED STROKE

PROTOCOL
Dr Obaid Ashraf

 Stroke is defined by the abrupt onset of

neurological deficit that is attributable to a
focal vascular cause.
If the cessation of flow lasts for more than a few
minutes, infarction results.
When blood flow is quickly restored, brain tissue
can recover fully and the patient's symptoms are
only transient---TIA
The standard definition of TIA requires that all
neurologic signs and symptoms resolve within 24
h regardless of whether there is imaging evidence
of new permanent brain injury; stroke has occurred
if the neurologic signs and symptoms last for >24
h.

Significance of Penumbra
The concept of ischemic penumbra was
originally introduced by Astrup et-al in
1981 and defined as an area of reduced CBF
with electrical failure but preserved ion
homeostasis
The transition from ischemia to irreversible
infarction depends on both the severity & the
duration of the diminution of blood flow.
A penumbra can be evaluated both on CT (on
which it is evidenced by a discrepancy in
perfusion parameters) and on MRI (on which
it is indicated by a mismatch between
diffusion and perfusion parameters).

Acute Stroke Evaluation on CT

Unenhanced CT
Widely available.
Can be performed
quickly.
IV Contrast not
required.
Can easily rule out
hemorrhage and
other stroke
mimics

Low sensitivity in
1st 24hrs.

NCCT 2 hrs after onset of hemiparesis:

shows hyperdense L MCA s/o IV thrombosis.

NCCT :hypodensity & obscuration in Rt lentiform

nucleus & loss of gray-white interface in lateral

Importance of Window Settings

Lev et al showed sensitivity and
specificity of 57% & 100%, respectively,
for acute ischemic stroke detection at
unenhanced CT with the use of standard
window settings (width, 80 HU; center, 20
HU). Sensitivity increased to 71% with a
change of window width and center level
settings to 8 HU and 32 HU, respectively,
without a loss in specificity.

NCCT 2 hrs after onset of left hemiparesis

Quantitation of Ischemic Involvement

European Cooperative Acute Stroke Study
trial showed that involvement of more than
1/3rd of the MCA territory depicted at
unenhanced CT was a criterion for the
exclusion of patients from thrombolytic
therapy because of a potential increase in the
risk for hemorrhage.
Subsequent studies with use of the one third
rule showed poor interobserver correlation.
Alberta Stroke Program Early CT Score
(ASPECTS) was proposed in 2001 as a means
of quantitatively assessing acute ischemia on CT
images by using a 10-point topographic scoring.

10 regions of MCA territory each with a score of 1

(to be deducted from a total of 10)

CT Angiography
CT angiography typically involves a thinsection volumetric helical acquisition
that extends from the aortic arch to the
circle of Willis using time-optimised
bolus of iodinated contrast (350400mg/ml) @ 3.5-4ml/sec
Post-processing : MIP ; MPR images are
viewed on the work-station.

 Assess the status of carotid and vertebrobasilar system for thrombi, atherosclerotic
disease, dissection, collateral flow.
Helpful in treatment planning by localising
occlusion site.
Helpful in basilar artery strokes as post
fossa is not well assesed on NCCT and
brainstem is frequently not included in
Perfusion CT.
Helps detect the presence of a filling defect in
the vessel caused by true arterial thrombosis
with a sensitivity of 89%.
However, Minor thrombi are frequently missed
in the daily clinical setting if no correlation is
performed with perfusion.

Acute stroke in a 43-year-old woman: Initial CT normal.

F/U CT at 36 hrs and CTA reveal BA thrombosis

Acute Stroke :1.5 hrs evolution (NCCT, CTA source image and MIP)

 CTA can also be used to asses the

collateral flow which affects prognosis:
0 No collaterals.
1 Visible collaterals to peripheray of
ischemic site.
2 Complete irrigation of ischemic site
by collateral flow.
3 Normal antegrade flow.

 CTA source Imaging: includes a wholebrain analysis of the source images with a
narrow window provides a whole-brain
perfused blood vol map showing
areas of ischemic hypoattenuation (more
sensitive than NCCT in early phases, good
correlation with DWI).
CTA source Imaging provides accurate
whole brain information for perfusion CT
maps.

CT Perfusion Imaging
Perfusion CT is performed by monitoring only the
first pass of an iodinated contrast agent bolus
through the cerebral circulation.
Continuous cine imaging over the same slab of
tissue (132 sections) during the dynamic
administration of a small (50-mL), high-flow
contrast material bolus (injection rate, 45 mL/sec).
The contrast agent passes through the brain tissue,
causing a transient hyperattenuation that is
directly proportional to the amount of contrast
material in the vessels and blood in that region.
This principle is used to generate time-attenuation
curves for an arterial ROI, a venous ROI, and each
pixel.

Time attenuation curves for arterial and

venous ROIs

 The generated arterial and venous curves

must be studied to detect possible poor
timing of the contrast material bolus (the
curve must have included an initial plane
before rising and a decline before the end
of the acquisition) and to distinguish
good arterial input function or venous
outflow function (the venous curve must
be higher than and represent a 12-second
delay after the arterial curve).
The evaluation of perfusion imaging data
requires the use of complex
deconvolution algorithms to produce
perfusion maps.

Perfusion Parameters
1. CBV: It is the volume of blood per unit
of brain tissue (normal 4-5 ml/100gm).
2. CBF: It is the vol of blood flow per unit
of brain tissue per minute. (normal 5060 ml/100g/min)
3. MTT : Time diff b/w arterial inflow and
venous outflow.
4. Time to peak enhancement.

1. MTT is calculated by performing a

mathematical technique called
deconvolution on the regional timeattenuation curve of each pixel with
respect to the arterial curve (arterial
input function).
2. CBV is calculated by dividing the area
under the curve in a parenchymal pixel
by area under the curve in an arterial
pixel.
3. CBF is calculated by the formula :
CBF=CBV/MTT.

 CT perfusion imaging in acute stroke is based

on the hypothesis that the penumbra shows
either:
(a) increased mean transit time with
moderately decreased cerebral blood flow
(60%) and normal or increased cerebral blood
volume (80%100% or higher) secondary to
autoregulatory mechanisms or
(b) increased mean transit time with markedly
reduced cerebral blood flow (30%) and
moderately reduced cerebral blood volume
(60%), whereas infarcted tissue shows
severely decreased cerebral blood flow (30%)
and cerebral blood volume (40%) with
increased mean transit time.

CT perf map of CBV & CBF

Types of CT Perfusion Imaging Techniques

1. Dynamic Contrast-enhanced .
2. Perfused blood vol mapping :
Unenhanced CT followed by CTA.
Quantitative CBV values are obtained by
subtracting unenhanced CT image data
from CTA source image data. Subtracted
image is reffered to as Perfused Bloodvol map.
Advantage : Whole brain can be
evaluated.
Disadv: cannot evaluate CBV & MTT

Results of CT Perfusion Mapping

The greatest regional abnormalities on CT
perfusion maps in acute stroke have been
demonstrated for MTT values, followed by
CBF and CBV values.
The MTT maps also may be the most
sensitive indicators of stroke, with
changes in CBF & CBV being more
specific for distinguishing ischemia from
infarction.

 Several studies have shown that the CBV

map depicts the lesions seen at DWI,
helping predict the infarcted brain tissue
& the CBF map depicts the altered area
seen at perfusion MR imaging, which is
related to the ischemic area. Hence, the
salvageable brain tissue is equivalent to
CBF CBV.
Some authors have reported a threshold
for core infarction when CBV is less
than 2L/min and for ischemic tissue
when MTT is over 145%.

 Wintermark et al,showed that CT

perfusion imaging was more accurate
than was unenhanced CT for detecting
stroke (75.7%86.0% vs 66.2%, P .01)
and determining the extent of stroke
(94.4% vs 42.9%, P .01).
MTT maps were more sensitive, while
cerebral blood flow and cerebral blood
volume maps were more specific for
detection of acute stroke.

Acute Stroke (2.5 hrs from onset) ; NCCT, CBV and CBF maps

Summary map and post-thrombolysis CT

CBV, CBF and MTT maps

Role of MR Imaging in Acute Stroke Evaluation

A thorough evaluation of acute stroke can

be performed by using a combination of
1. Conventional MR imaging.
2. MR angiography.
3. DWI.
4. Perfusion-weighted MR imaging.

Conventional MR Imaging
More sensitive and specific than CT within
1st few hours.
MR sequenses typically used include:
1. T1-SE.
2. T2 FSE.
3. FLAIR.
4. T2W GRE.
5. Post GAD T1W-SE.
Conventional MR is less sensitive
than DWI in 1st few hrs after stroke.

 Typical findings include :

1. Hyperintense signal on FLAIR & T2W with
resultant loss of grey-white differentiation.
2. Sulcal effacement.
3. Mass effect.
4. Loss of arterial flow-voids on T2W.
5. Stasis of contrast within vessels in the
affected area.
6. Low-signal-intensity or high-signal-intensity
vessel sign due to intravascular thrombus
can be seen on MR images obtained with a
T2*GRE or FLAIR, respectively.
7. T2WGRE sequences are sensitive for ICH.

MRA
Like CTA, MRA is useful for detecting
intravascular occlusion due to a thrombus
and for evaluating the carotid bifurcation
in patients with acute stroke.
Time-of-flight MRA and contrast-enhanced
MR angiography are commonly used to
evaluate the intracranial and extracranial
circulation.

TOF MR Images.

Diffusion-weighted MR Imaging
Underlying Principles: Stroke causes
excess intracellular water accumulation,
or cytotoxic edema, with an overall
decreased rate of water molecular
diffusion within the affected tissue.
Mearsurement of net water molecular
motion was 1st attempted by Stejskal &
Tanner using T2W SE with two extra
equal gradients in opposite directions.
This technique resulted in signal loss.
Tissues with higher rate of diffusion
undergo a greater signal loss in a given

Acute Post Circulation Stroke on DWI

 Current diffusion-weighted MR imaging

techniques employ echo-planar
sequences that are highly resistant to
patient motion.
Image acquisition can be performed in a
few minutes and has increased sensitivity
to signal changes due to molecular
motion.
Diffusion coefficient obtained from
orthogonal diffusion-weighted MR images
in all three planes is called the apparent
diffusion coefficient (ADC).

Time Course of Thromboembolic infarction

 For acute ischemia detection within the

first 6 hours after onset, diffusionweighted imaging is reported to have
high sensitivity and specificity, of 88%
100% and 86%100%.

False Negative DWI

Small lacunar
brainstem infarcts.
Small Deep grey
nuclei infarcts.
Ischemic areas that
are still viable (may
have abnormal
perfusion)

False Positive DWI

Abscess.
Tumor.

Perfusion-weighted MR Imaging
While diffusion-weighted MR imaging is
most useful for detecting irreversibly
infarcted tissue, perfusion-weighted
imaging may be used to identify areas of
reversible ischemia as well.
1. Exogenous Method (using MR contrast
agent).
2. Endogenous Method (Arterial spin
labelling).

Underlying Principle
Exogenous techniques are typically susceptibility
based and depend on T2* effects and use Dynamic
susceptibility-weighted T2* sequence.
The passage of an intravascular MR contrast agent
through the brain capillaries causes a transient loss
of signal because of the T2* effects of the
contrast agent.
MR perfusion imaging technique involves tracking of
the tissue signal changes caused by susceptibility
(T2*) effects to create a hemodynamic timesignal
intensity curve.
Perfusion maps (CBV, CBF, MTT) are calculated in a
similar fashion as in CT perfusion using
deconvolution analysis.

 Arterial spin labeling technique exploits the spins of

endogenous water protons to measure perfusion.
The spin polarity of arterial protons flowing into the
imaging plane is inverted by applying
radiofrequency pulses upstream from the imaging
section. The effect on image intensity is measured
as these protons perfuse the brain tissue.
Two sets of images are obtained, one that is flow
sensitive and one that is insensitive to flow.
The image obtained by subtracting the flowsensitive image from the flow-insensitive
image provides a measure of the labeled
protons that perfused the imaging plane.
Perfusion parameters then can be calculated from
the subtracted image.

APPLICATIONS OF PERFUSION-DIFFUSION MISMATCH

PDM is defined as a ratio of a

perfusion:diffusion lesion vol >1.2 or a diff
of >10-15ml.
The PDM theory introduced in the late 1990s
was used:
1. As a practical selection tool for stroke treatment.
2. Second, to test the hypothesis that patients with
PDM pattern will benefit from treatment, while
those without mismatch pattern will not.
3. Third, PDM was applied as a surrogate measure
for stroke outcome. Some studies suggested
that the abnormality from PWI can be used to
predict the lesion growth or final infarct volume.

Acute stroke (2 hrs) :PWI >DWI

PWI >DWI

OPTIMAL DEFINITION OF PDM

Concept of conventional PDM has been
challenged by many studies indicating
that DWI overestimates the infarct core
by including a part of penumbra ; and
PWI overestimates penumbra by
including regions of benign oligemia.

 Many methods have been advised to optimise

the conventional PDM:
1. Serial measurements of PDM:
.PDM is strictly time-dependent and most
cases of PDM occur within 6 hrs of onset.
2. Threshold method for defining PDM:
Rohi et al reported that cutoff values of relative
CBF < 0.59 and MTT > 1.63 were optimal in
distinguishing the benign oligemia and real
penumbra.
Oppenheim et al suggested that the ADC
values best excluded penumbra (7.82
0.8210-4 mm2/s) from benign oligemia (8.23
0.4110-4 mm2/s)

POTENTIAL ALTERNATIVES FOR PDM

1. pH-weighted imaging-PWI or DWI
mismatch:
There is decrease in pH in the area of
penumbra due to anaerobic metabolism.
.Sun et-al detected pH-dependent amide
proton tranfer b/w endogenous peptides
and tissue water and obtained pH-WI.
.pHW-DWI mismatch then represented
the true penumbra whereas PWI-pHWI
mismatch would represent benign
oligemia.

2. MR Thermometry-DWI mismatch:
Increased temp of brain tissues is common in
acute ischemia.
Brain temperature (T) can be measured
noninvasively with MRSI.
For each voxel, temperature can be calculated
from the apparent chemical shift of NAA peak,
using the following formula: T = 37 + 100
(NAApeak - 2.035), where a chemical shift of 2.035
ppm was found in healthy control subjects with
an assumed brain temperature of 37 .
Using this approach, Karaszewski et-al found
tissues were hotter in potential penumbra than
likely infarct core which was in turn hotter than
normal brain

3. BOLD Imaging based penumbra:

Based on the fact that OEF is significantly
increased in penumbra.
DeoxyHb is used as a marker for OEF that
can be visualised on T2* based BOLD
imaging as signal loss.
Geisler et-al applied quantitaive T2*
based BOLD imaging in acute stroke and
found signal reduction in penumbra due
to increased OEF.

4. MRA-DWI mismatch:
Defined as MRA score of 3 (for
intracranial ICA & M1 ; 1=normal flow ,
2= reduced flow, 3=occlusion) and DWI
lesion vol of < 25ml ; or a MRA score of 2
and DWI vol < 15ml.
More prevalent in intracranial large artery
atherosclerotic stroke.
5. PET based estimation of penumbra:
Gold standard for detection of penumbra.
No readily available/affordable.

THANK YOU