considers the intravascular and extra-vascular spaces as a single compartment. Fick’s principle calculates tissue perfusion based on conservation of mass within the system. estimates the perfusion either from the maximal slope or the peak height of the same tissue concentration curve normalized to the arterial input function
Intravascular and extra vascular spaces as separate compartments and measures perfusion parameters. Patlak analysis - patlak analysis is a nuclear medicine processing technique that is used to determine the rate constant of tissue uptake of a tracer from the vascular space by using the value of tracer concentration in tissue and blood
to create the greatest peak enhancement and hence the optimal signal-intensity-to noise ratio for CTP map calculation.
CT perfusion physics and its application in Neuroimaging
CT PERFUSION PHYSICS AND ITS
Dr. Suhas Basavaiah
Resident (MD Radio-diagnosis)
• In 1979, Leon Axel first proposed a method of determining the tissue perfusion from dynamic contrast enhanced
• First attempt was made with stable Xenon.
• Due to requirement of rapid image acquisition and processing, it was confined to research studies.
• The advent of spiral CT systems in 1990s enabled perfusion CT to be performed with conventional CT.
• It is a technology that allows functional evaluation of tissue vascularity.
• It measures the temporal changes in tissue density after intravenous injection of a contrast medium bolus using a
series of dynamically acquired CT images.
• Because of rapid technologic advancements in multidetector CT (MDCT) systems and the availability of
commercial software, perfusion CT offers a wide array of clinical and research applications.
• major clinical applications - acute stroke and oncology.
• rapid scan timing and faster image processing - modality of choice for evaluation of the status of cerebral
• In the field of oncology it has found use in diagnosis, staging, prognostic evaluation, and monitoring of response to
• perfusion CT has the potential to become the preferred technique for the assessment of tumor response to
PERFUSION CT TECHNIQUE: BASIC PRINCIPLES
• The fundamental principle - temporal changes in tissue attenuation after intravenous administration of iodinated
• enhancement of tissues - iodine concentration is an indirect reflection of tissue vascularity and vascular physiology.
• After intravenous injection of the iodinated contrast, the ensuing tissue enhancement can be divided into two
phases based on its distribution in the intravascular or extravascular compartment.
• In the initial phase, the enhancement is due to the contrast within the intravascular space, and this lasts
approximately first 40 to 60 seconds.
• Later, in the second phase, due to passage of contrast from intra to extra-vascular compartment, tissue
enhancement results from contrast distribution.
• Thus, in the initial phase, the enhancement is determined by blood flow (BF) and blood volume (BV), whereas in
the second phase, by the vascular permeability to the contrast.
• The temporal changes in tissue attenuation after contrast injection can be recorded quickly, and by applying
appropriate mathematic modeling, tissue perfusion can be quantitated.
TERMS COMMONLY USED IN CT PERFUSION
Blood Flow or Perfusion
• Flow rate through vasculature in tissue region (mL per 100 g/min)
BV or Blood volume
• Volume of flowing blood within a vasculature in tissue region (mL per 100 g)
MTT or Mean transit time
• Average time taken to travel from artery to vein (Seconds)
PS or Permeability surface
• Total flux from plasma to interstitial space (mL per 100 g/min)
Time to peak enhancement
• the time from the beginning of contrast material injection to the maximum concentration of contrast
CT perfusion parameters can be analyzed by –
• Compartmental analysis
• Deconvolution analysis
Both the analytical methods require obtaining time attenuation data from the arterial input for estimation of
tissue vascularity and to correct for inter patient variations in bolus geometry.
SINGLE COMPARTMENT MODEL
• Fick’s principle - tissue perfusion based on conservation of mass within the system
• maximal slope or the peak height of the tissue concentration curve normalized to the arterial input
DUAL COMPARTMENT MODEL
• Patlak analysis - determine the rate constant of tissue uptake of a tracer from the
vascular space by using the value of tracer concentration in tissue and blood
• quantifies the passage of contrast from intravascular space into the extra vascular space.
• It is the most commonly used algorithm because of its advantages over other methods:
I. the absence of unrealistic assumptions about venous outflow
II. the ability to use lower intravenous infusion rates.
• Mean Transit Time is calculated by performing a deconvolution of the regional (tissue) time-attenuation curve with
respect to the arterial time-attenuation curve (arterial input function).
• Cerebral Blood Volume is calculated by dividing the area under the time-attenuation curve in a parenchymal pixel
by the area under the time-attenuation curve in an arterial pixel.
• The central volume equation then can be solved to obtain the cerebral blood flow.
• visual assessment of the venous time-attenuation - normalization of perfusion parameters because it helps correct
the data for partial volume averaging effects.
• In the ideal case, we would examine the inflow to, and the outflow from every region (i.e., pixel).
• Thus, we would expect the outflow signal to be equal to the inflow signal convolved with the impulse
Tracer Measurement over time
• The response to an impulse input is the
distribution of all possible transit times
through the system.
• h(t)dt is the fraction of “particles” that leave
the system between t and t+Dt
• The Mean transit time is at the center of
mass of the distribution, h(t). I.e., 1st
• Rather than measure at inflow and outflow, we make observations of something equivalent to
I. signal at ~inflow (the arterial function) and,
II. signal from the entire pixel.
• The integral H(t), of the histogram is all the tracer that has LEFT the system.
• The residue function, R(t), describes all tracer still remaining, at time t and NOT yet drained from the system.
Our observations are related to R(t)
• In the case of an ideal input, the view from within the pixel would look like:
Why measure CBV?
• 1. Vasodilation (increased CBV ) may occur distal to narrowed carotid arteries.
• 2. Decreased CBV/CBF may reflect slowed cerebral circulation.
• 3. CBV necessary to measure residual Oxygen in tissue
• The evaluation of brain perfusion is based on the central volume principle, according to which
CBF = CBV/MTT
• The two most commonly used CT perfusion imaging techniques are dynamic contrast material–enhanced
perfusion imaging and perfused-blood-volume mapping.
DYNAMIC CONTRAST-ENHANCED CT
• Based on the multicompartmental tracer kinetic model and performed by monitoring the first pass of an
iodinated contrast agent bolus through the cerebral circulation.
• The contrast agent bolus causes a transient increase in attenuation that is linearly proportional to the amount of
contrast material in a given region.
• This principle is used to generate time-attenuation curves for an arterial ROI, a venous ROI, and each pixel.
• The perfusion parameters then can be calculated by employing mathematical modeling techniques such as
• Both the arterial and the venous ROIs are chosen in large vessels that course in a direction nearly
perpendicular to the plane of CT acquisition (the axial plane).
• Color-coded perfusion maps of cerebral blood volume, cerebral blood flow, and mean transit time are
then generated at the workstation
• The baseline CT study should have 3 components: unenhanced CT, vertex to-arch CT angiography (CTA), and
dynamic first-pass CTP.
• cardiac multidetector row CT (MDCT) for the detection of possible left atrial appendage thrombus is optional.
• Contrast Administration - A contrast bolus of 35–45 mL is administered via power injector at a rate of 7 mL/s,
with a saline “chaser” of 20–40 mL at the same injection rate. The contrast used should typically be a high
concentration, ideally 350–370 g/dL of iodine.
• The CTP imaging protocol has been performed at 80 kV, rather than the more conventional 120–140 kV.
Theoretically, given a constant milliampere-second (typically 200 mAs), this kilovolt setting would reduce the
administered radiation dose.
• maximum degree of vertical coverage could potentially be doubled for each bolus by using a “shuttle-mode”
Tube voltage 80 - 100kV
Tube current 200 mAs/ Auto mAs
Detector coverage 40mm
Scan time 31 seconds
Table pitch 1:0.984; 39.37
Noise index 11.57
Gantry rotation time 0.4 sec
Slice interval 5mm
Reconstruction slice thickness 0.625
Reconstruction intervals 3.75 to 5.0mm
Number of shuttle pass 18
Scan type Helical
Filter kernel Soft
PERFUSION CT PROTOCOL
• A typical perfusion CT protocol consists of a baseline acquisition without contrast enhancement, followed by a dynamic
acquisition performed sequentially after intravenous injection of CM
• The dynamic image acquisition includes a first-pass study, a delayed study, or both, depending on the pertinent
physiologic parameter that needs to be analyzed.
Unenhanced CT Acquisition
• Provides wide coverage to include the organ of interest.
• Serves as a localizer to select the appropriate tissue area to be included in the contrast-enhanced dynamic imaging
Dynamic CT Acquisition
• The imaging volume is chosen on the basis of the unenhanced CT images
• The first-pass study for perfusion measurements comprises images acquired in the initial cine/helical phase for a total of
approximately 40 to 60 seconds.
• For permeability measurements with the compartmental model, images are acquired every 10 to 20 seconds.
• Define ROIs for artery and vein. Most
commonly selected artery is ACA and
vein is superior sagittal sinus.
• The new CT perfusion software has
automated vessel selection capability.
Normal :By convention, all color maps are coded RED for higher values and BLUE for lower values.
OTHER TECHNICAL CONSIDERATIONS
• Motion during data acquisition can lead to image misregistration and can cause errors in the estimation of
• breath-holding instructions to the patient, use of abdominal Straps , use of motility-inhibiting agents, to curtail
bowel peristalsis during the perfusion examination of bowel.
• In addition, luminal distention with water or saline is encouraged for studies of hollow viscera to enable optimal
• Metallic stents, prostheses, and surgical implants cause beam-hardening artifacts and can negatively influence the
• areas with excessive tumor necrosis or those located along organs with motion (in chest examinations) and areas
near metallic prostheses or stents should be avoided.
• A major concern of perfusion CT is the risk for exposure to ionizing radiation, especially in patients
who require serial perfusion studies.
• In patients with compromised renal function, contrast-induced nephropathy is a valid concern and
should be dealt with cautiously
• Unenhanced CT followed by CT angiography of the brain can be used to assess arterial patency and tissue
perfusion during the infusion of a single bolus of contrast.
• Cerebral blood volume values are obtained by subtracting the unenhanced CT image data from the CT
angiographic source image data.
• degree of parenchymal enhancement depends on the actual cerebral blood volume and the quantity of contrast
material reaching the tissue during the image acquisition - the subtracted images are referred to as perfused-blood-
• Can depict entire brain parenchyma, however cannot quantitate CBF and MTT.
PITFALL AND CONTROVERSIES
• the accuracy of the ﬂow values obtained has not been fully validated.
• Perfusion CT uses an intravascular tracer to measure CBF, which reﬂects a different physiologic mechanism than that
of PET and xenon CT.
• Few studies reported systematically low values for CBF as measured with perfusion CT, compared with xenon CT.
• Larger ROIs may result in greater volume averaging of gray and white matter - lower quantitative values for CBF,
compared with the results obtained when smaller ROIs are used.
• It is probably more accurate to use an input artery from the normal side. Extra-cranial arteries can be better choices.
• The reproducibility of perfusion CT has also not been fully validated.
• restricted anatomic coverage
• Increased radiation exposure.
CTP IN STROKE
• Stroke is a leading cause of mortality and morbidity in the developed world.
• The goals of an imaging evaluation are
I. to establish a diagnosis as early as possible
II. to obtain accurate information about the intracranial vasculature
III. to identify critically ischemic or irreversibly infarcted tissue (“core”) and to identify severely ischemic but
potentially salvageable tissue (“penumbra”).
• This information can guide triage and management in acute stroke.
ACUTE STROKE IMAGING PROTOCOL
• When acute stroke patients present within 6 hours of the onset of symptoms - un-enhanced CT or with
• Hemorrhage at unenhanced CT or >1/3 MCA territory - not treated with thrombolytic drugs.
• ischemia of < 1/3 MCA territory, those who present <3 hours after the onset of acute stroke - intravenous
• 3–6 hours after the onset of symptoms - CT angiography and CT perfusion imaging to assess the intracranial and
neck vessels and detect any penumbra.
• Intraarterial therapy is usually considered for patients in whom a penumbra is seen.
• Patients in whom no penumbra is seen are not usually treated with thrombolytic drugs
ROLE OF CT IN ACUTE STROKE EVALUATION
The three key CT techniques—
CT Perfusion Imaging
• Widely available
• Performed quickly
• Does not involve the administration of intravenous contrast material.
• It can:
I. help identify a hemorrhage (a contraindication to thrombolytic therapy)
II. help detect early-stage acute ischemia by depicting features such as the hyperdense vessel sign, the
insular ribbon sign, and obscuration of the lentiform nucleus.
III. identification and quantification of parenchymal involvement in acute stroke.
Hyperdense Vessel sign
Axial unenhanced CT images in a proximal segment of the left MCA in a 53-year-old man
(a) and a distal segment of the left MCA in a 62-year-old woman
(b), obtained 2 hours after the onset of right hemiparesis and aphasia, show areas of hyperattenuation (arrow)
suggestive of intravascular thrombi
Obscuration of lentiform nucleus
Acute ischemia of the lenticulostriate
territory result in obscuration of the
lentiform nucleus, which appears
May be seen within 2 hours after the
onset of a stroke
Axial unenhanced CT image obtained in a 53-year-old man shows
hypoattenuation and obscuration of the left lentiform nucleus
(arrows), which, because of acute ischemia in the lenticulostriate
distribution, appears abnormal in comparison with the right
Insular Ribbon Sign
• Acute ischemia of the insular
cortex, which is susceptible to
early and irreversible ischemic
damage, also causes local
hypoattenuation, which results in
the so-called insular ribbon sign
Axial unenhanced CT image, obtained in a 73-year-old
woman 21/2 hours after the onset of left hemiparesis,
shows hypoattenuation and obscuration of the posterior
part of the right lentiform nucleus (white arrow) and a loss
of gray matter–white matter definition in the lateral
margins of the right insula (black arrows).
• Widely available technique for assessment of both the intracranial and extracranial circulation.
• Its utility in acute stroke lies in –
I. demonstrating thrombi within intracranial vessels and
II. evaluating the carotid and vertebral arteries in the neck .
• (a) Unenhanced CT image in a 72-year-old woman with acute right hemiplegia shows hyperattenuation in a proximal segment of the
left MCA (arrows).
Axial (b) and coronal (c) reformatted images from CT angiography show the apparent absence of the same vessel segment (arrows).
The presence of an intravascular thrombus in this location was confirmed by comparing the reformatted images with the CT source
images (not shown).
• Intra-arterial thrombolysis may be more efficacious - acute stroke and a significant thrombus burden
• demonstration of a significant thrombus burden can guide appropriate therapy in the form of
intraarterial or mechanical thrombolysis.
• identification of carotid artery disease and visualization of the aortic arch - cause ischemic event and
guidance for the interventional neuroradiologist.
CT PERFUSION IMAGING
• The imaging volume is chosen on the basis of the unenhanced CT images
• The arterial ROI is typically chosen in either of the two anterior cerebral arteries (if they are unaffected) or
in the unaffected MCA.
• The venous ROI is usually placed over the superior sagittal sinus, transverse sinus, or torcular herophili.
• At least one of the axial sections passes through the level of the basal ganglia.
• cerebral blood volume, cerebral blood flow, and mean transit time are quantitated.
• CT perfusion maps then can be generated in a short time at an appropriate workstation
• A penumbra can be evaluated based on perfusion parameter mismatch.
SIGNIFICANCE OF A PENUMBRA
• brain tissue is exquisitely sensitive to ischemia, because of the absence of neuronal energy stores.
• complete absence of blood flow, the available energy for 2–3 minutes.
• In acute stroke, ischemia is incomplete and injured area of the brain receives collateral blood supply
from uninjured arterial and leptomeningeal territories.
• Acute cerebral ischemia may result in a irreversibly infarcted tissue core surrounded by a peripheral
region of stunned cells that is called a penumbra .
• Evoked potentials in the peripheral region are abnormal, and the cells have ceased to function, but
this region is potentially salvageable with early recanalization .
Schematic of brain involvement in acute stroke shows a core of irreversibly infarcted tissue surrounded by a
peripheral region of ischemic but salvageable tissue referred to as a penumbra. Without early recanalization, the
infarction gradually expands to include the penumbra.
CBF CBV MTT
Infarcted core Markedly
Penumbra Moderately decreased Normal or
Gray matter White matter
CBF 60 – 85 ml/100
25 – 40 ml/100
CBV 4 ml/100 g 2 ml/100 g
MTT (s) 4 s 4.8 s
Normal Perfusion CT Parameters
CTP Parameters in Ischemic stroke
HYPOTHESIS IN STROKE
• The clinical application of CT perfusion imaging in acute stroke is based on the hypothesis -
• the penumbra shows either
(a) Increased MTT with moderately reduced CBF and normal or increased CBV - autoregulatory mechanisms or
(b) increased MTT with markedly reduced CBF and moderately reduced CBV,
• the infarcted tissue shows severely decreased CBF (<30%) and CBV with increased MTT
• quick visual analysis for color changes that are indicative of perfusion deficits or with a more tedious measurement
of perfusion parameters within ROIs placed in multiple regions.
• CT perfusion maps of
(a )cerebral blood volume
(b ) cerebral blood flow show, in the left hemisphere, a region of decreased blood volume (white oval) that corresponds to the
ischemic core and a larger region of decreased blood flow (black oval in b) that includes the ischemic core and a peripheral region of
The difference between the two maps (black oval = white oval) is the penumbra.
• Acute stroke in a 65-year-old man with left hemiparesis. CT perfusion maps of
( a )cerebral blood volume
(b) cerebral blood flow
(c ) and mean transit time
show mismatched abnormalities (arrows) that imply the presence of a penumbra.
The area with decreased blood volume represents the ischemic core, and that with normal blood volume but decreased blood flow
and increased mean transit time is the penumbra.
• CTP imaging is more accurate than unenhanced CT for detecting stroke and determining the extent of stroke
• MTT more sensitive, while CBF & CBV maps are more specific for detection of acute stroke.
• Hence CT angiography and CT perfusion studies in patients with acute stroke could be performed, processed,
and interpreted quickly
• Investigators in subsequent trials showed good clinical outcomes of thrombolytic drug therapy.
• Thrombolytic therapy may be made more effective by performing appropriate CTP rather than relying on
the time of onset as the sole determinant of selection.
OTHER APPLICATIONS OF CT PERFUSION IN
• chronic cerebral ischemia from carotid artery stenosis - CBF is preserved initially because of the
• The cerebrovascular reserve - vasodilatation ability of cerebral arteries to compensate for CBF
• It is necessary to quantify - risk of ischemia, which can be triggered by any hemodynamic stress, and
requires intervention to increase CBF.
• Endovascular Hemodynamic stress - tolerance test (acetazolamide administration)
• Frequent complication after aneurysmal subarachnoid hemorrhage (SAH)
• MTT maps are reviewed for arterial territories with prolonged MTT values. Such territory is
considered at risk for vasospasm and then evaluated.
• If CTA of the corresponding artery is abnormal, the diagnosis of vasospasm is made
• Finally, the arterial territories are carefully assessed for a decrease in cortical CBF values.
• If present, the latter prompts a conventional angiogram for possible endovascular treatment.
• distinguishing between patients with preserved and deranged autoregulation.
• detect altered brain perfusion - compression by an epidural/subdural hematoma
• require more aggressive and early treatment to prevent intracranial hypertension.
• Normal brain perfusion or hyperemia - favorable outcome, and oligemia in case of unfavorable
Patient who fell from a 6-m height, admitted with a Glasgow Coma Scale score of 9. Neurological examination
in the emergency room revealed an asymmetry of tone and deep tendon reflex involving both right upper and lower
limbs. Admission contrast-enhanced cerebral CT demonstrated a displaced left parietal skull fracture, associated with a
large cephalhematoma. A small left parieto-occipital epidural hematoma (white arrowhead) and a small contusion area
(white star) could also be identified on the conventional CT images. PCT demonstrated a much wider area of brain
perfusion compromise (white arrows), with involvement of the whole left temporal and parietal lobes, the latter showing
TEMPORARY BALLOON OCCLUSION
• Performed in patients in whom prolonged temporary occlusion is considered as part of the surgical or
• in conjunction with a quantitative analysis of CBF can help identify patients who will not tolerate permanent
• use of an absolute CBF value of < 30 mL/100 g/min as a criterion for the success or failure.
• patients undergo angiography and balloon occlusion, during which time they are clinically evaluated for 30
• Patients who pass the clinical portion of the examination are brought to the CT suite with the balloon in place.
• A perfusion CT scan is obtained with the balloon inﬂated and again with the balloon deﬂated.
• The balloon is reinﬂated, 1,000 mg of acetazolamide is injected intravenously, and a ﬁnal perfusion CT scan is
Utility of perfusion CT in oncology include:
(1) lesion characterization (differentiation between benign and malignant lesions);
(2) identification of occult malignancies;
(3) provision of prognostic information based on tumor vascularity
(4) monitoring therapeutic effects of the various treatment regimens, including chemoradiation and
• increased angiogenic activity and neovascularization results in increased blood volume and hyperpermeability
related to the immature vessels – increase in rCBV
• Microvascular permeability increase - aggressiveness of tumors; reduction in permeability in response to
antiangiogenic therapy correlates with decreased tumor growth.
• quantification of the abnormal vasculature within tumors - assessment of tumor aggressiveness.
• measure vascular physiologic changes by virtue of changes in the contrast enhancement characteristics of tissues.
• perfusion CT allow earlier assessment of response with treatment with newer antiangiogenic drugs effect than
conventional methods, which rely on tumor size.
• perfusion CT is clearly a viable alternative to other modalities used to measure cerebral perfusion.
• technique is fast and available for most standard spiral CT scanners equipped with the appropriate software.
• It is indispensable in imaging of patients with acute stroke.
• It can also be utilized in evaluation of patients with other cerebrovascular diseases.
• It may also be helpful in diagnosis and subsequent treatment response in patients with a variety of tumors.
• By virtue of its temporal resolution, it can replace PET in tumor imaging.
• It can also be utilized in imaging the disorders of liver, lungs, pancreas and pelvis.
• Further investigations are necessary to determine the accuracy, reliability, and reproducibility of the quantitative