Perfusion CT (pCT) is a convenient, safe, and feasible imaging modality that provides a wealth of information about cerebrovascular perfusion. This information can be used to evaluate patients and stratify appropriate treatment. The authors discuss the use of pCT in the assessment of acute stroke and other cerebrovascular disorders.
is Chief Resident and
is Chairman of the Department of Radiology, Winthrop-University
Hospital, Mineola, NY.
Radiologic evaluation of patients with cerebrovascular disease
has evolved with the introduction of new technology. Specifically,
multislice computed tomography (MSCT) has emerged as an imaging
modality that can assess the extent and severity of cerebral
Perfusion CT (pCT) can provide rapid, high-resolution information
that can be used to assess and stratify treatment of patients with
acute stroke. In this article, the authors discuss the use of pCT
in the assessment of acute stroke and other cerebrovascular
Cerebral perfusion is defined as the steady-state delivery of
blood to cerebral tissue through capillaries. Perfusion is measured
in mL/100 g tissue/minute and under normal conditions cerebral
perfusion is 50 to 60 mL/100 g/minute. An acute stroke is caused by
an abrupt localized reduction in cerebral blood flow that causes a
reduction in cerebral perfusion. This results in cerebral ischemia
and, ultimately, infarction of the compromised cerebral tissue.
However, there is often viable tissue surrounding the ischemic core
or penumbra. Although the penumbra has a limited blood supply,
metabolism is preserved and this tissue can recover if the insult
is reversed within a narrow time frame.
Currently, thrombolysis remains the treatment of choice for acute
ischemic stroke within 3 hours after onset of symptoms.
Beyond this 3-hour window, no single trial has proven the efficacy
of thrombolytic therapy; however, meta-analysis suggests that there
is a significant reduction in mortality and disability if treatment
occurs within a 3- to 6-hour window.
However, thrombolysis carries a risk-as high as 10%-of intracranial
Therefore, further stratifying patients who will benefit from
thrombolytic therapy is vital for optimal management of patients
with acute stroke.
Patients presenting with acute stroke are first identified based
on neurologic evaluation. The radiologic work-up of acute stroke
begins with an unenhanced CT of the brain. A major purpose of
cranial CT is to assess for the presence of intracranial
hemorrhage. The presence of an intracranial hemorrhage classifies
the acute neurologic event as a hemorrhagic stroke and essentially
excludes the patient from obtaining thrombolytic therapy. CT is
also used to exclude other lesions, such as tumors or abscesses,
which can mimic the clinical presentation of stroke. Most
importantly, CT is used to detect the suspected area of ischemia.
Unfortunately, despite the search for CT signs of acute cerebral
infarction, such as a hyperdense middle cerebral or basilar artery,
obscuration of the lentiform nucleus or loss of the gray-white
junction along the cerebral cortex, the initial CT study is normal
in 60% of cases.
A technique that can improve the sensitivity of CT for the
detection of acute stroke and further stratify patients who will
benefit from thrombolytic therapy is necessary and is now
Evaluation of cerebral blood flow using pCT
There are various techniques available to evaluate cerebral
blood flow and perfusion. Previous investigators have established
that cerebral blood flow can be accurately determined by
intravascular injection of a bolus of contrast agent followed by
rapid image acquisition.
With respect to CT, cerebral blood flow and perfusion can be
measured with the use of a nondiffusible agent, such as an iodine
contrast agent, or the use of a diffusible inert gas indicator,
such as xenon. Imaging is based upon measuring steady-state
delivery of a blood-borne indicator to a given region of cerebral
Perfusion CT utilizes an iodinated contrast agent, which passes
through the cerebral arteries and vascular bed. Temporal changes in
the CT attenuation are recorded. With this bolus-tracking
technique, analysis of time versus concentration curves can provide
information regarding cerebral blood flow (CBF), mean transit time
(MTT), time to peak enhancement (TTP), and cerebral blood volume
(CBV). These parameters can be derived wtih postprocessing software
that uses either a maximum slope model to calculate CBF or a
deconvolution analysis to calculate MTT and CBV.
In the latter case, CBF can be calculated, according to the central
volume principle, from the quotient of CBV and MTT (CBF =
Perfusion CT has been shown to accurately predict final cerebral
infarct size in the acute phase.
In addition, pCT has been shown to be both safe and feasible; the
median time to complete the exam was 23 minutes in one study of 53
The accuracy of pCT can be further enhanced by using a vascular
pixel elimination technique.
This method excludes contrast enhancement within large blood
vessels that would ordinarily result in overestimation of the
quantitative value of cerebral blood flow.
A pCT study begins with an unenhanced CT of the brain (Figure
1). Provided there are no contraindications to further evaluation,
the radiologist then localizes a level of the brain for further
study based upon the neurologic evaluation of the patient. Current
CT scanner technology allows for longitudinal coverage of 2 to 3 cm
of the brain during each infusion of contrast. An extended anatomic
area can be evaluated using the "toggling table" technique;
however, there is loss of temporal resolution because less data is
acquired at each location. Increased signal-to-noise and
lower-quality images may compromise results with this technique.
Although the area to be localized depends upon the clinical
symptoms and the suspected area of involvement, generally one of
the levels includes the basal ganglia, which allows evaluation of
the anterior, middle, and posterior cerebral distributions.
With a 4-detector-row scanner, scanning is initiated, and
repetitive sections are sequentially obtained through the 4
contiguous 5-mm thick slice planes, which span 20 mm of cerebral
tissue. The injector is started at the same time as the scanner,
and 50 mL of low osmolar nonionic contrast agent (300 mg/mL iodine
concentration) is injected at a rate of 5 mL/sec. This rate
requires 18- to 20-gauge intravenous access. The acquisition
continues for 40 seconds. After 5 minutes, a second axial
acquisition is performed, again using 50 mL of contrast agent,
which allows an additional 20 mm of cerebral tissue to be studied.
Thus, a total of 4 cm of brain parenchyma is covered along the
vertical axis, or z-axis.
The first step in processing the information obtained from the
acquisition consists of selecting a region of interest (ROI) on a
magnified view of one image. An arterial enhancement function or
curve for the selected ROI is calculated using commercially
available automated perfusion function software. A composite image
is then created using all four axial slices, and a color-coded
version of the composite image is generated to assist the operator
in identifying the ROIs. The operator draws a line to separate the
right and left cerebral hemispheres. This line allows the program
to identify a mirrored ROI on the contralateral side for
comparison. In bolus tracking, the time course of the changing
attenuation reflects the changes in iodine contrast agent and is
plotted on a time versus concentration curve. A relative value for
CBF can be calculated by integrating the area under this curve,
which is proportional to the fractional vascular volume of cerebral
tissue. The simultaneous measurement of cerebral tissue and
arterial attenuation as a function of time enables the calculation
of MTT. According to the central volume principle, perfusion,
represented by CBF, is equal to the CBV divided by the MTT. Data,
including CBF, CBV, MTT, and TTP, are calculated for each ROI.
Once the above values are calculated, areas of infarction and the
penumbra can be identified. Previous investigators have established
that a CBV drop below 2.5 mL/100 g is indicative of infarcted
tissue, as is CBF <34% when compared with the opposite
(unaffected) side; values that are higher than this threshold but
still abnormally low indicate the penumbra.
Hunter et al
have proposed a probability curve for regional cerebral infarction
using normalized pCBV in patients who present with acute stroke.
Using this curve can help predict the likelihood of infarction for
any given area of cerebral tissue.
pCT versus other perfusion modalities
Perfusion techniques have been used for many years to gain
information regarding tissue physiology. Xenon, a small,
biologically inert gas, has been used in its radioactive form as a
freely diffusible agent to measure cerebral perfusion for more than
More recently, xenon has been used as a contrast agent to measure
tissue perfusion, as it can attenuate X-rays in a similar fashion
as iodine. Xenon-enhanced CT has been shown to be accurate in the
measurement of cerebral perfusion.
In fact, xenon-enhanced CT was used to validate perfusion CT data,
which demonstrated accurate and reliable results.
However, xenon-enhanced CT is available in only a limited number of
institutions and, therefore, is not a diagnostic option for most
patients. Moreover, xenon-enhanced CT requires the use of special
equipment for administering the xenon gas. This can be a cumbersome
procedure and requires a fairly cooperative patient.
Positron emission tomography (PET) is also a very accurate
procedure for assessing cerebral perfusion. This technology is not
widely available, however, and its longer imaging time makes it
less efficacious in the evaluation of acute cerebrovascular events.
Magnetic resonance imaging (MRI) using diffusion-weighted sequences
has been shown to be highly accurate in the evaluation of acute
stroke, with sensitivities ranging from 94% to 100%.
Diffusion-weighted imaging has been shown to be superior to both
conventional MR and unenhanced CT in the evaluation of acute
When using MRI to identify the penumbra, a combination of perfusion
MRI and diffusion MRI yields the greatest accuracy, using the
diffusion-weighted studies to identify the region of infarction and
subtracting these areas from the perfusion MR images to identify
When compared with diffusion and perfusion MRI, pCT has been shown
to be equivalent in identifying the cerebral penumbra in patients
with acute stroke.
There are advantages and disadvantages of pCT when compared with
perfusion MRI. The greatest advantage of pCT is that, in addition
to being widely available, all patients who are candidates for
thrombolysis will require an unenhanced CT to exclude intracranial
hemorrhage. Perfusion CT adds only a small amount of additional
time, requires no specialized hardware or equipment, and generates
additional information within the same visit. While MRI is also
increasingly available in most institutions, it is still difficult
to perform an emergent MRI study on a critically ill patient. The
greatest disadvantages of pCT are the exposure of the patient to an
additional dose of ionizing radiation, the requirement for the
injection of a nonionic intravenous contrast agent, and, currently,
the inability to evaluate the entire brain.
Other pCT applications in cerebrovascular disease
Only a few studies have examined the use of pCT in the
evaluation of patients with chronic cerebral ischemia. MR
techniques to evaluate chronic ischemia are well-established.
However, patients with pacemaker devices and aneurysm clips are
precluded from MR imaging, and these techniques require rapid
scanner gradients and MR-compatible contrast injection devices that
are not widely available.
Perfusion studies (such as PET and xenon-enhanced CT) coupled with
reactivity to an acetazolamide challenge has been used to identify
patients who would benefit from invasive interventions to increase
regional blood flow.
Perfusion CT has been shown to be a useful tool in the
evaluation of chronic cerebral ischemia (Figure 2). Furukawa et al
found that, when compared with xenon-enhanced CT combined with an
acetazolamide challenge, pCT achieves similar values for relative
cerebral blood flow and can serve as an alternative method for the
evaluation of chronic cerebral ischemia. This may have utility in
the evaluation of flow disturbances that are associated with
carotid stenosis in patients with recurrent transient ischemic
attacks. Alternatively, it may be possible to assess the status of
the collateral circulation in patients with vascular occlusive
disease. Perfusion CT and CTA can be used in combination to study
patients with intracranial vasospasm following subarachnoid
hemorrhage. Other potential applications for pCT include the
evaluation of vascular steal phenomena, such as in subclavian
steal, arteriovenous malformations, and direct or indirect carotid
cavernous fistulas. With pCT, it may be possible to study the
sequelae of intracranial mass effect, such as those observed in
patients with subdural hematomas or other intracranial masses.
Certainly, pCT can be used as a postprocedural probe to assess the
efficacy of cerebrovascular revascularization procedures, such as
external carotid artery bypass, intra- or extracranial arterial
stenting, angioplasty, papaverine infusion, or
Perfusion CT is a convenient, safe, and feasible imaging
modality that provides a wealth of information about
cerebrovascular perfusion, including identification of the
penumbra. It promises to afford clinicians an efficient means to
further stratify patients, thereby improving upon the existing
algorithm in the management of patients with both acute and chronic
cerebrovascular diseases. Many questions still remain to be
answered, and although further research is required before making
its application widespread, preliminary results made by the
principle investigators and the enthusiasm that the radiologic
community has shown for pCT predict that these questions will soon