Perfusion-computed tomography (CT) was developed to assist in the evaluation of cerebral blood flow.  It provides a detailed study of cerebral blood perfusion, which is intended to identify ischemic brain regions, especially within the first few hours after stroke onset.  In clinical practice, perfusion CT requires the use of a non-diffusible indicator, such as an iodine contrast agent.  This document addresses the use of perfusion-computed tomography for cerebral perfusion imaging.

For information regarding cerebral perfusion studies using magnetic resonance imaging (MRI), please refer to RAD.00046 Cerebral Perfusion Studies using Diffusion and Perfusion Magnetic Resonance Imaging.

Investigational and Not Medically Necessary: 

Cerebral perfusion-computed tomography is considered investigational and not medically necessary for all indications including, but not limited to, the evaluation of cerebral ischemia.

Perfusion CT (PCT) can be performed with a diffusible gas indicator such as xenon (Xe), however in clinical practice an iodinated contrast agent is typically used, given the limited availability of medical grade Xe.  Images are obtained in the cine mode depicting the cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT).  These parameters can be combined to identify the core and penumbra.  One of the appeals of PCT is that the standard imaging of individuals with stroke symptoms is an unenhanced (plain) CT scan in the emergency room to both diagnose acute infarction and exclude intracranial hemorrhage.  Therefore, a PCT can be added to a plain CT scan both to increase the detection of early strokes and to distinguish between the ischemic core and the penumbra.  When plain CT, PCT and CT angiography are used together, the combined imaging test may be referred to as multimodal CT.  Multimodal CT is designed to demonstrate the infarcted tissue (plain CT or PCT), the site of arterial occlusion (CT angiography) and its hemodynamic consequences (PCT).  One area of investigation involves the assessment of the different zones of ischemia following a stroke.  For example, following an occlusion of a major intracerebral artery (i.e. stroke), a gradient of hypoperfusion emerges, characterized as the ischemic core of irreversible damage, surrounded by a region of relative hypoperfusion, known as the "penumbra."  Tissue within the penumbra is functionally impaired, but can be salvaged by effective reperfusion, such as with thrombolytic treatment.  Currently candidates for thrombolytic therapy are primarily identified by the time since symptom onset, with a target window of opportunity of 3 hours, based on randomized trials of tissue plasminogen activator (tPA).  However, it is hypothesized that the subset of individuals with a penumbra persisting beyond 3 hours could still be potentially salvaged with thrombolytic therapy.  Therefore, one potential role of cerebral perfusion CT is its use to distinguish between the ischemic core and the penumbra and to identify candidates for thrombolytic therapy. 

In 2008, Provenzale and colleagues published a systematic review of both CT and MRI perfusion imaging in the assessment of acute cerebrovascular disease.  The authors identified 8 different roles for this imaging:

1. Perfusion to guide treatment
2. Predict clinical outcomes
3. Predict final infarct size
4. Determine effects of a therapy on perfusion abnormalities
5. Characterize infarct types or to better understand infarct-like processes
6. As a comparison with diffusion weighted imaging, but no outcome measure
7. Compare perfusion with an imaging technique other than MRI
8. Solely as an entry criteria (for clinical trials)

For the purposes of this document, studies of clinical utility are the basis of medical necessity, specifically data demonstrating that the results of the test can be used to direct and improve clinical decision making and treatment.  Of the categories listed above, only the first category, perfusion to guide treatment, clearly relates to clinical decision making.  For individuals with symptoms of acute stroke, the key management decisions are related to whether or not the person is a candidate for thrombolytic therapy, based on infarct size, size of penumbra or time from symptom onset.  Studies in category 2 and 3 essentially validate perfusion imaging as a test and provide information that could be used in decision making.  Category 4 included articles that documented the effect of treatment on the perfusion imaging deficits, but this information was not used to guide the clinical management of individuals.  Categories 5 to 7 explore the underlying pathophysiology of acute ischemia.  Category 8 described research studies where results of perfusion imaging defined trial eligibility. 

The authors did not identify any article of CT perfusion that fell into category 1.  In categories 2 and 3, the authors identified 46 articles that used a variety of trial designs and outcomes to explore the predictive value of perfusion imaging.  While the authors concluded that in general the studies showed the perfusion defects are related to clinical outcomes, i.e. the clinical validity, the authors point out that there is still insufficient data to determine how this information can be used in making decisions regarding treatment, i.e. the clinical utility.  

In 2007, the American Heart Association published clinical guidelines for the early management of adults with ischemic stroke. (Adams 2007).  These guidelines gave perfusion CT the following Class IA recommendation: "Multimodal CT and MRI may provide additional information that will improve diagnosis of ischemic stroke." However despite this recommendation the text of the guidelines notes, "The role of perfusion CT and CT angiography in making acute treatment decisions has not yet been established." Therefore, the AHA guidelines suggest that there is adequate evidence documenting the clinical validity of perfusion CT, but not the clinical utility. 

The Agency for Healthcare Research and Quality (AHRQ) published an Evidence Report/Technology Assessment on Acute Stroke: Evaluation and Treatment in 2005 which addressed multiple issues regarding CT perfusion and angiography, in terms of how these modalities affect the safety and efficacy of thrombolytic therapy for acute ischemic stroke.  The AHRQ Report stated that, "Prospective use of CT perfusion and angiography techniques in patient selection for thrombolysis was not identified" (AHRQ, 2005).

Both perfusion CT and perfusion/diffusion MRI (discussed in RAD.00046)  are imaging techniques that have been investigated to provide more detailed diagnostic and prognostic information related to acute and chronic cerebral ischemia, primarily related to stroke.  For example, plain computed tomography (i.e. without contrast) is highly sensitive in the detection of acute intracranial hemorrhage, but is much less sensitive in the identification of ischemic brain lesions within the first few hours of stroke onset.  Chronic, progressive, occlusive disease and ischemia from vasospasm are also conditions that have been difficult to diagnose with current imaging techniques.

Cerebral (Ischemic) Infarction: An area of coagulation necrosis in brain tissue, (i.e., tissue death), due to local anemia resulting from obstruction of the circulation to the area.

Perfusion-computed tomography: This newer imaging technique uses either a diffusible inert gas indicator, (i.e., xenon/Xe) or a non-diffusible indicator, (such as iodine) to measure cerebral blood flow (CBF), as well as other measures, such as mean transit time (of cerebral blood through the cerebral arteries and vascular bed) and cerebral blood volume; the ability to measure these perfusion parameters has been made possible with the development of high-speed helical/spiral CT scanners.

Stroke: A generic term used to represent any one or all of a group of disorders, including cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage; stroke is characterized by a non-convulsive, focal, neurologic deficit that lasts greater than 24 hours in duration.

Subarachnoid Hemorrhage: Bleeding into the subarachnoid space, characterized by the sudden onset of severe headache that is typically dramatic; there may also be rapid alteration of consciousness, or vomiting, or both;  other symptoms include minimal headache, nuchal rigidity (stiff neck), fixed neurologic deficits, cranial nerve palsy, drowsiness, confusion, stupor, or coma.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

When services are Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Hoeffner EG, Case I, Jain R, et al. Cerebral perfusion CT: technique and clinical applications.  Radiology. 2004; 231(3):632-644.
2. Kloska SP, Nabavi DG, Gaus C, et al.  Acute stroke assessment with CT: Do we need multimodal evaluation.  Radiol. 2004; 233(1):79-86.
3. Koenig M, Kraus M, Theek C, et al.  Quantitative assessment of the ischemic brain by means of perfusion-related parameters derived from perfusion CT.  Stroke. 2001; 32(2):431-437.
4. Moustafa RR, Baron JC.  Clinical review: imaging in ischaemic stroke – implications for acute management.  Crit Care. 2007; 11(5):227-236.
5. Provenzale JM, Shah K, Patel U, McCrory DC. Systematic review of CT and MR perfusion imaging for assessment of acute cerebrovascular disease. AJNR Am J Neuroradiol. 2008; 29(8):1476-1482.
6. Schellinger PD, Fiebach JB, Hacke W. Imaging-based decision making in thrombolytic therapy for ischemic stroke: present status. Stroke. 2003; 34(2):575-583.
7. Schramm P, Schelllinger PD, Klotz E, et al.  Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration.  Stroke. 2004; 35(7):1652-1658.
8. Touho H, Karasawa J. Evaluation of time-dependent thresholds of cerebral blood flow and transit time during the acute stage of cerebral embolism: a retrospective study. Surg Neurol. 1996; 46(2):135-145.
9. Wintermark M, Flanders AE, Velthuis B, et al.  Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke. 2006; 37(4):979-985.
10. Wintermark M, Reichhart M, Thiran JP, et al. Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients. Ann Neurol. 2002; 51(4):417-432. 

Government Agency, Medical Society, and Other Authoritative Publications:

1. Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults With ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Stroke. 2007; 38(5):1655-1711.  Available at: http://stroke.ahajournals.org/cgi/reprint/38/5/1655  Accessed on June 9, 2011.
2. Agency for Healthcare Research and Quality.  Acute stroke: evaluation and treatment. Health Technology Evidence Reports (Summary). 2005; (127):1-7.  Available at: http://www.ahrq.gov/downloads/pub/evidence/pdf/acutestroke/acstroke.pdf.  Accessed on June 9, 2011.
3. Centers for Medicare and Medicaid Services. National Coverage Determination: Computerized Tomography. NCD #220.1. Effective November 22, 1985. Available at: http://www.cms.hhs.gov.  Accessed on June 9, 2011.

Cerebral Perfusion Computed Tomography