Imaging in Ischemic Stroke
REVIEW
Imaging in Ischemic Stroke
State of the Art
N. Venketasubramanian*, Myrna Justina**
* Senior Consultant of Neurosonology, National Neuroscience Institute (NNI), Singapore
**Medical Officer, Mitra Keluarga Bekasi Hospital, Indonesia
ABSTRACT
Exciting advances in anatomical imaging have greatly improved our capacity to detect
pathologic process in nervous system, localize these processes in the nervous system
precisely, and predict the type of disease. The rapid evolution of techniques of anatomical
imaging has occurred in parallel with developments in physiologic imaging.
Cerebrovascular disease and stroke
Stroke is the third most common cause of death in
developed countries. The age adjusted annual death rate from
stroke is 116 per 100,000 population in the USA, some 200
per 100,000 in the UK, some 12% of all deaths; it is higher in
black African population than in Caucasian. Stroke is
uncommon below the age of 40 years and is more common in
males. The death rate following a stroke is around 25%.
Hypertension is the most important treatable risk factors.
Stroke is decreasing in the 40-60 age range as hypertension is
treated; however, in the elderly, it remains a major cause of
morbidity and mortality.
1
Stroke is a complex, heterogeneous disease with several
major subtypes. The sudden onset of focal sensory loss,
weakness, or speech disorder raises the possibility of cerebral
ischemia or infarction. The three most common causes of
cerebral infarction are atherothrombotic occlusion, embolism,
and hypoperfusion.
2
Rapid and accurate assessment is crucial
for treatment, since recombinant tissue plasminogen activator
provides effective treatment for acute ischemic infarction in
the absence of cerebral hemorrhage if given within three hours
after onset.
3
Through a careful medical history and a complete
physical examination, the most likely vascular territories and
related causes of a particular stroke can be identified. Primary
symptoms, and vascular territories of ischemic stroke are
summarized in Table 1.
2
Table 1. Primary Symptoms, and Vascular Territories of Ischemic
Stroke
Primary Symptoms
Vascular Territories
Aphasia + right side weakness
Middle Cerebral Artery (Dominant)
Neglect + left side weakness
Middle Cerebral Artery (Non-
dominant)
Weakness on one side (no other
findings)
Lacunar syndrome
Weakness + sensory loss on one
side (no other findings)
Lacunar syndrome
Sensory loss on one side (no other
findings)
Lacunar syndrome
Weakness of leg more than arm,
incontinence, personality change
Anterior Cerebral Artery
Isolated homonymous visual field
deficit
Posterior Cerebral Artery
Bilateral weakness + cranial nerve
deficits + ataxia
Basilar artery
Refers to strokes with defined symptom complexes that do not include
aphasia, change in consciousness, or other cortical symptoms; they appear to
be caused by occlusion of small subcortical or brain stem arterioles, although
they may also result from micro-emboli.
Various Imaging Techniques
Passage of x-radiation through tissue attenuates the
radiation, and the intensity of the exiting radiation can be
measured with sensitive film or detectors. X-ray computed
(CT) permits the examination of tissue by the same principle
Cermin Dunia Kedokteran No. 157, 2007
181
Imaging in Ischemic Stroke
as conventional x-ray imaging, except that radiation passes
successively through tissue from multiple different directions,
detectors measure the degree of attenuation of the exiting
radiation relative to the incident radiation, and computers
integrate the information and construct the images in cross
section. Administration of contrast material increases x-ray
attenuation owing to the high atomic number and electron
density of the iodinated compounds used. CT has the
advantages of widespread availability, short study time,
sensitivity for detection of calcifications and acute
hemorrhages, and excellent visualization of the anatomy of
bone, such as skull base and vertebrae. The use of intravenous
contrast medium with CT allows examination of the integrity
of the blood brain barrier, which consists of tight junctions
between endothelial cells of blood vessels and astrocytes.
4
Placement of tissue in a strong magnetic field causes
certain naturally occurring isotopes (atoms) within the tissue
to line up within the field, orienting the net tissue
magnetization in the longitudinal direction. Many isotopes are
affected, but current MRI uses signals derived from
1
H, the
most plentiful endogenous isotope. When in a magnetic fields,
these atoms do not orient precisely with the axis of the field,
but wobble a few degrees off center. Application of different
gradient magnetic fields to the tissue under study permits
reconstruction of the signal from individual volume units in
space. Use of the intravascular contrast material gadolinium-
diethylenetriamine pentaacetic acid (gadolinium-DTPA) with
MRI alters the magnetic susceptibility of adjacent tissue,
thereby providing information about the integrity of the blood-
brain barrier.
4
Positrons are the antimatter equivalent of electrons. The
collision of an electron and a positron annihilates both
particles, converting their masses to energy in the form of two
photons (gamma rays) that leave the brain at an angle of 180°
to each other and can be detected. The radioligands most
frequently used to emit positrons are [18
F
] fluorodeoxyglucose
for measuring cerebral metabolic of glucose
5
and [
18
O] water
for determining cerebral blood flow.
6
PET and SPECT use this
highly versatile method of studying cerebral function. SPECT
uses principles similar to those of PET but the radioligands
decay to emit only a single photon.
4
Preferred Imaging Procedures in the Ischemic Strokes
Head CT scans are excellent for detecting large
hemorrhages, tumors, and other structural lesions that can
produce symptoms mimicking acute stroke symptoms. The
differences in X-ray attenuation (density) between bone, brain,
and cerebrospinal fluid (CSF) makes it possible to distinguish
normal and infracted tissue, tumors, extravasated blood or
edema.
1, 7
Currently, CT is the brain-imaging method of choice
for the assessment of acute ischemic injury to determine
whether hemorrhage is present, because it is highly sensitive
to hemorrhage, rapid, widely available, relatively low cost,
and noninvasive (Fig. 1).
8
Hyperdensity of major cerebral
vessels is an important sign that can be detected by CT within
minutes of vessel thrombosis and hours before parenchymal
changes occur.
9
The finding of a hyperdense vessel can be
used in the appropriate clinical setting to consider a patient for
aggressive endovascular lytic therapy.
MRI, particularly diffusion-weighed and perfusion-
weighed MRI is more sensitive than CT, particularly for early
pathologic changes of ischemic infarction because it is
superior in detecting brain edema.
10,11
lacunar infarctions, and
strokes involve the brain stem region.
12
MRI is superior to CT
in detecting small lacunar lesions, particularly those located
deep within cerebral hemispheres and in brain stem and
cerebellum (Fig. 2). Another advantage of MRI is that the
cerebral vessels can be imaged using a magnetic resonance
angiography protocol, allowing non-invasive imaging of both
the extracranial and intracranial large cerebral vessels.
13
New
MRI technologies, such as magnetic resonance diffusion,
perfusion, and spectroscopy, may provide information on the
metabolic status of, and blood flow to, ischemic brain
regions.
14
Carotid ultrasound, and carotid duplex can image
atherosclerotic lesions at the bifurcation of the carotid arteries.
Continuous-wave Doppler employs two separate transducers,
one to send and one to receive the Doppler signal. Since the
transmitted Doppler signal is continuous, continuous-wave
Doppler is not limited by aliasing and is particularly useful for
detecting a wide range of frequencies. Pulsed Doppler allows
sampling at discrete locations in vessels and has improved
depth resolutions. Duplex ultrasound combines high resolution
gray scale imaging of carotid vessels with physiologic blood
flow information provided by Doppler techniques (usually
pulsed Doppler).
15
Compared with angiography, the overall
accuracy of either carotid duplex or magnetic resonance
angiography can image atherosclerotic lesions at the
bifurcation of the carotid arteries.
16,17
Transverse carotid
images of the bifurcation help establish the optimal orientation
for longitudinal scans in which Doppler spectral analysis will
be performed (Fig. 3).
15
Intracranial atherosclerosis is responsible for up to 10% of
strokes and transient ischemic attacks (TIAs). When
extracranial internal carotid disease is excluded as the
mechanism of these strokes and TIAs, it may be important for
Cermin Dunia Kedokteran No. 157, 2007
182
Imaging in Ischemic Stroke
clinicians to identify intracranial arterial stenosis, particularly
when warfarin is considered a therapeutic option. Initial direct
noninvasive test included continuous-wave and pulsed
Doppler imaging, which quantified stenosis according to peak
frequency shifts, detected in a vessel. In these instances,
Transcranial Doppler (TCD) is often used as a screening test
to identify patients requiring invasive cerebral arteriography.
TCD, another noninvasive technique, provides information
about flow direction and velocities in the major intracranial
vessels.
18
The use of the monitoring probe even allows
continuous and instantaneous information on changes in
cerebral hemodynamics. Currently, TCD is of established
value in assessing patterns and extent of collateral circulation
in patients with known regions of severe stenosis or occlusion.
Significant stenosis causes increased velocities maximal at the
site of obstruction (Fig. 4). Marked acceleration is seen at
stenosis exceeding 80%. Reversed and markedly accelerated
flow in the ipsilateral cerebral artery suggests the presence of
collateral flow across the communicating artery from contra-
lateral circulation (Fig. 5).
19
Cerebral angiography remains the gold standard for
diagnosing large vessel vascular disease and intracranial
vasculitides. It is indicated particularly in young patients with
stroke, in cases of suspected vasculitis or vascular dissection
(Fig. 6).
20
However, recent studies have shown that magnetic
resonance angiography (MRA) and CT angiograms are at least
as sensitive as angiography for diagnosing dissections.
21, 22
On
the other hand, there are few prospective data that TCD and
MRA in combination can effectively replace angiography at
this time for identification of intracranial atherosclerosis. The
recently launched Stroke Outcomes and Neuroimaging of
Intracranial Atherosclerosis (SONIA) study will provide some
answers to these concerns.
19
Impact on implementing guidelines
Early diagnostic testing should be selected to establish the
anatomical regions and structures involved and the cause of
infarction, since early intervention and subsequent secondary
prevention should vary accordingly.
23
Because ischemic stroke
results from an occluded blood vessel, reversing or bypassing
the occlusion should decrease the adverse effects of the
stroke.
24
If the diagnosis of ischemic stroke without
hemorrhage can be made and all inclusion and exclusion
criteria are met (Table 2), treatment with intravenous
thrombolytic therapy may be indicated.
23
The FDA approved
this treatment on the basis of the results of the National
Institute of Neurological Disorders and Stroke (NINDS) rt-PA
study
3
in which 624 ischemic stroke patients were treated with
t-PA 0.9 mg/kg BW (10% given as an intravenous loading
dose and the remainder administered intravenously over 1
hour, with a maximum dose of 90 mg) within 3 hours of stroke
onset. The value of this activator administered more than three
hours after the onset of symptoms is not known.
Table 2. Major Treatment Guidelines for Using Recombinant Tissue
Plasminogen Activator (t-PA) in Stroke Patients
Inclusion criteria
· Ischemic stroke in any circulation.
· Ability to establish the time of onset unambiguously.
· Ability to begin t-PA therapy within 3 hours of symptom onset.
· Head CT scan without any evidence of hemorrhage or other complicating
disease
· Age 18 years or older.
Exclusion criteria
· Stroke or serious head trauma within the past 3 months.
· Any past history of any type of brain hemorrhage (subarachnoid or
intracerebral) or suspicion of a subarachnoid hemorrhage.
· CT scan showing evidence of hemorrhage, arteriovenous malformation,
tumor or aneurysm.
· Systolic Blood Pressure > 185 mmHg or Diastolic > 110 mmHg (on 3
occasions, 10 minutes apart).
· Seizure preceding or during current stroke.
· Active internal bleeding.
· Coagulopathy with abnormal prothrombin or partial thromboplastin time,
or platelet count < 100,000 per microliter.
· Rapidly improving or minor symptoms.
· Coma or stupor.
· Major surgery or invasive procedures within the past 2 weeks.
· Gastrointestinal or genitourinary hemorrhage within the past 3 weeks.
· Noncompressible arterial puncture or biopsy within the past week
· Glucose < 50 mg/ dl or > 400 mg/ dl.
· Evidence of active pericarditis, endocarditis, septic emboli, recent
pregnancy, lactation, or inflammatory bowel disease,
· Active alcohol or drug abuse.
Local intraarterial thrombolysis performed with a
microcatheter that is placed into, beyond, and proximal to an
arterial occlusion is in use worldwide. In the past, the agent
most commonly studied was urokinase; intraarterial t-PA and
prourokinase have mainly been used in recent investigational
studies. Approximately 40 percent of the patients who undergo
this treatment have complete arterial recanalization, and
approximately 35 percent have partial recanalization. These
rates of recanalization are higher than those that have been
reported for patients who undergo intravenous thrombolytic
therapy.
23
For patients who have a nondisabling stroke (or TIAs)
resulting from high-grade extracranial carotid artery disease,
Cermin Dunia Kedokteran No. 157, 2007
183
Imaging in Ischemic Stroke
carotid endarterectomy (CEA) is recommended, assuming the
patient is a good surgical candidate. CEA in these patients
decreases the occurrence of ipsilateral stroke or death from
26% to 9% at 2 years. The efficacy of CEA in patients with
moderate stenosis (50-69%) is less than in patients with high-
grade disease. The benefits of CEA require a low rate of
perioperative complications. Complication rates of no more
than 5% to 6% are desirable. Studies have evaluated the safety
and efficacy of carotid artery angioplasty and stenting in these
patients.
24
REFERENCES
1.
Clarke CRA. Neurological disease. In: Kumar P, Clark M. Clinical
Medicine. 5th ed. Edinburgh,Toronto. WB Saunders; 2002: p.1123-224.
2.
Caplan LR. Diagnosis and treatment of acute ischemic stroke. JAMA
1991; 266: 2413-18.
3.
The National Institute of Neurological Disorders and Stroke rt-PA
Stroke Study Group. Tissue plasminogen activator for acute ischemic
stroke. N Engl J Med 1995; 333: 1581-87.
4.
Gilman Sid. Imaging the brain. N Engl J Med 1998; 338: 812-20.
5.
Meltzer CC, Zubieta JK, Brandt J, Tune LE, Mayberg HS, Frost JJ.
Regional hypometabolism in Alzheimer's disease as measured by
positron emission tomography after correction for effects of partial
volume averaging. Neurology 1996; 47: 454-61.
6.
Bottini G, Corcoran R, Sterzi R, et al. The role of the right hemisphere
in the interpretation of figurative aspects of language: a positron
emission tomography activation study. Brain 1994; 117: 1241-53.
7.
Adams HP Jr, Brott TG, Crowell RM et al. Guidelines for the
management of patients with acute ischemic stroke: A statement for
healthcare professionals from a Special Writing Group of the Stroke
Council, American Heart Association. Stroke 1994; 25: 1901-14.
8.
Moulin T, Cattin F, Crepin-Leblond T et al. Early CT signs in acute
middle cerebral artery infarction: predictive value for subsequent infarct
locations and outcome. Neurology 1996; 47: 366-75.
9.
Sasiadek M, Wasik A, Marciniak R. CT appearance of bilateral, acute
thrombosis of the main cerebral arteries. Comput Med Imaging Graph
1990; 14: 89-90.
10.
Warach S, Gaa J, Siewert B, Wielopolski P, Edelman RR. Acute human
stroke studied by whole brain echo planar diffusion-weighed magnetic
resonance imaging. Ann Neurol 1995; 37: 231-41.
11.
Lutsep HL, Albers GW, DeCrespigny A, Kamat GN, Marks MP,
Moseley ME. Clinical utility of diffusion weighted magnetic resonance
imaging in the assessment of ischemic stroke. Ann Neurol 1997; 41:
574-80.
12.
Kertesz A, Black S, Nicholson L, Carr T. The sensitivity and specificity
of MRI in stroke. Neurology 1987; 37: 1580-85.
13.
Riles TS, Eidelman EM, Litt AW et al. Comparison of magnetic
resonance angiography, conventional angiography, and duplex scanning.
Stroke 1996; 23: 341-6.
14.
Fisher M, Prichard JW, Warach S. New magnetic resonance techniques
for acute ischemic stroke. JAMA 1995; 274: 908-11.
15.
Carroll BA. Carotid Sonography. Radiology 1991; 178: 303-13.
16.
Riles TS, Eidelman EM, Litt AW et al. Comparison of magnetic
resonance angiography, conventional angiography, and duplex scanning.
Stroke 1992; 23: 341-6.
17.
Patel MR, Kuntz KM, Klufas RA, et al. Preoperative assessment of the
carotid bifurcation. Can magnetic resonance angiography and duplex
ultrasonography replace contrast arteriography? Stroke 1995;26:1753-8.
18.
Caplan LR, Brass LM, DeWitt LD et al. Transcranial Doppler
ultrasound: present status. Neurology 1990; 40: 696-700.
19.
Babikian VL, Feldmann E, Wechsler LR, et al. Transcranial Doppler
Ultrasonography: Year 2000 Update. J. Neuroimaging 2000; 10: 101-15
20.
Wolpert SM, Caplan LR. Current role of cerebral angiography in the
diagnosis of cerebrovascular disease.Am J Roentgenol 1992; 159: 191-7.
21.
Stringaris K, Liberopoulos K, Giaka E, Kokkinis K. Three-dimensional
time-of-flight MR angiography and MR imaging versus conventional
angiography in carotid artery dissections. Int Angiol 1996; 15: 20-25.
22.
Sellar RJ. Imaging blood vessels of the head and neck. J Neurol
Neurosurg Psychiatry 1995; 59: 225-37.
23.
Brott T, Bogousslavsky J. Treatment of acute ischemic stroke. N Engl J
Med 2000; 343: 710-22.
24.
Albert MJ. Diagnosis and treatment of ischemic stroke. Am.J.Med.
1999; 106: 211-21.
Figure
1. A CT Scan shows a large, subacute, nonhemorrhagic
infarction in the territory of the left middle cerebral artery
(arrowheads). Reprint request was permitted by Dr. Gilman at
the Department of Neurology, University of Michigan, Ann
Figure 2. An axial T
2
-weighted MRI shows a 1-cm lacunar infarction
(arrow) in the region of the left internal capsule. Reprint
request was permitted by Dr. Gilman at the Department of
Neurology, University of Michigan, Ann Arbor, MI 48109-
Cermin Dunia Kedokteran No. 157, 2007
184
Imaging in Ischemic Stroke
Figure 3. Early focal atherosclerotic changes (arrows) are seen at the
carotid bifurcation. The normal vessel wall configuration is
seen proximally (arrowhead) on this longitudinal scan.
Permission is granted by The Radiology Society of North
America (RSNA). E-mail: mstrassner@rsna.org
Figure 4. Stenosis of the left Middle Cerebral Artery (MCA) at 64 mm,
with V = 225 cm/s. Reprint request was permitted by Dr.
Ramani at the National Neuroscience Institute, Singapore. E-
Figure 5. Low velocity and pulsatility in the Middle Cerebral Artery
(MCA) at 48 mm ipsilateral to an occluded Internal Carotid
Artery (ICA). Reprint request was permitted by Dr. Ramani at
the National Neuroscience Institute, Singapore. E-mail:
Figure 6. Cerebral arteriogram in a patient with dysphasia and right
hemiplegia shows the embolic occlusion in the trunk of the left
middle cerebral artery (arrow). Reprint request was permitted
by Dr. Brott at the Department of Neurology, Mayo Clinic,
4500 San Pablo Road, Jacksonville, FL. 32224. E-mail:
Cermin Dunia Kedokteran No. 157, 2007
185
Document Outline