GENERAL INFORMATION
It is an expectation that all patients receive care/services from a licensed clinician. All appropriate supporting documentation, including recent pertinent office visit notes, 
laboratory data, and results of any special testing must be provided. If applicable: All prior relevant imaging results and the reason that alternative imaging cannot be 
performed must be included in the documentation submitted. 

Where a specific clinical indication is not directly addressed in this guideline, medical necessity determination will be made based on widely accepted standard of care criteria.
These criteria are supported by evidence-based or peer-reviewed sources such as medical literature, societal guidelines and state/national recommendations.

The guideline criteria in the following sections were developed utilizing evidence-based and peer-reviewed resources from medical publications and societal organization 
guidelines as well as from widely accepted standard of care, best practice recommendations.

Purpose
Cerebral perfusion computed tomography (CTP) is an imaging technique that provides quantitative evaluation of cerebral perfusion by generating maps of cerebral blood flow, cerebral blood volume, and mean transit time after passage of an IV contrast bolus through the region of interest. 

Summary of Evidence:
ACR-ASNR-SPR Practice Parameter For The Performance of Computed Tomography (CT) Perfusion in Neuroradiologic Imaging (2)

• Study Design: This document outlines practice parameters and technical standards for performing CT perfusion in neuroradiologic imaging. It is a consensus document developed by the American College of Radiology (ACR), the American Society of Neuroradiology (ASNR), and the Society for Pediatric Radiology (SPR).
• Target Population: The guidelines apply to both adult and pediatric patients undergoing CT perfusion for various indications.
• Key Factors: The document details the indications for CT perfusion, including ischemic stroke diagnosis, differentiation of salvageable ischemic penumbra from unsalvageable ischemic core, and evaluation of cerebral hemorrhage with secondary local ischemia. It also discusses the qualifications and responsibilities of personnel, specifications of the examination, and radiation safety.

ACR Appropriateness Criteria Cerebrovascular Diseases – Aneurysm, Vascular Malformation, and Subarachnoid Hemorrhage⁽¹⁾

• Study Design: This document provides appropriateness criteria for imaging in cerebrovascular diseases, including aneurysms, vascular malformations, and subarachnoid hemorrhage. It is an evidence-based guideline developed by a multidisciplinary expert panel.
• Target Population: The guidelines are intended for patients with cerebrovascular diseases, including those with known or suspected aneurysms, vascular malformations, and subarachnoid hemorrhage.
• Key Factors: The document emphasizes the importance of imaging in the diagnosis and management of cerebrovascular diseases. It provides recommendations for various imaging modalities, including CT perfusion, and discusses their appropriateness in different clinical scenarios.

ACR Appropriateness Criteria Cerebrovascular Diseases – Stroke and Stroke-Related Conditions⁽⁶⁾

• Study Design: This document outlines appropriateness criteria for imaging in stroke and stroke-related conditions. It is an evidence-based guideline developed by a multidisciplinary expert panel.
• Target Population: The guidelines apply to patients with stroke and stroke-related conditions, including those with transient ischemic attacks, acute ischemic stroke, and venous sinus thrombosis.
• Key Factors: The document provides recommendations for various imaging modalities, including CT perfusion, in the diagnosis and management of stroke. It discusses the role of CT perfusion in identifying the ischemic penumbra and guiding treatment decisions, particularly in the context of endovascular therapy.

ANALYSIS OF EVIDENCE
Shared Conclusions^(1,2,6):

• Importance of CT Perfusion: All three documents highlight the importance of CT perfusion in the diagnosis and management of cerebrovascular diseases and stroke. They emphasize its role in identifying ischemic penumbra, guiding treatment decisions, and evaluating cerebral hemorrhage with secondary local ischemia.
• Indications for Use: The documents agree on the primary indications for CT perfusion, such as ischemic stroke diagnosis, differentiation of salvageable ischemic penumbra from unsalvageable ischemic core, and evaluation of cerebral hemorrhage.
• Technical Standards and Safety: The ACR Practice Parameters and Ledbetter et al. both discuss the technical standards and radiation safety associated with CT perfusion, emphasizing the need for appropriate training and qualifications for personnel.

Differing Conclusions^(1,2,6):

• Target Population: While the ACR Practice Parameters apply to both adult and pediatric patients, Ledbetter et al. and Pannell et al. focus primarily on adult patients with specific cerebrovascular diseases and stroke-related conditions.

Overview^(1,2,6)
In summary, the three documents provide a comprehensive overview of the evidence for cerebral perfusion CT, highlighting its importance in the diagnosis and management of 
cerebrovascular diseases and stroke. They share common conclusions on the indications and technical standards for CT perfusion, while differing in their target populations and specific recommendations for various clinical scenarios.

Policy
INDICATIONS
In the following settings after initial CT and/or MRI has been performed or when MRI is contraindicated:

• In the non-acute setting^(1,2):
  • Pre-operative evaluation of cerebral blood flow in patients at high risk for developing cerebral hyperperfusion after carotid revascularization⁽³⁾
  • For assessment of cerebrovascular reserve by using acetazolamide challenge in individuals with intracranial vascular stenosis who are potential candidates for bypass surgery or neuroendovascular treatment⁽⁴⁾
  • For the assessment of microvascular permeability in individuals with intracranial neoplasms⁽⁵⁾
  • A follow-up study may be needed to help evaluate an individual’s progress after treatment, procedure, intervention, or surgery. Documentation requires a medical reason that clearly indicates why additional imaging is needed for the type and area(s) requested
• In the acute setting^(1,2,6):
  • For early detection of acute cerebral ischemia and infarct to determine the appropriateness of an intervention or procedure^(7,8)
    • For suspected infarct indicated by focal neurological deficit or initial imaging within 24 hours of known ischemic infarct⁽⁶⁾
  • Prediction of hemorrhagic transformation in acute ischemic stroke^(7–9)
  • Differentiating post-ictal paralysis or other stroke mimics from acute stroke after MRI has been completed or is contraindicated and will guide treatment⁽⁹⁾
  • For noninvasive evaluation of suspected vasospasm related cerebral ischemia/infarction and/or delayed cerebral ischemia after subarachnoid hemorrhage when transcranial Doppler cannot be done or is indeterminate⁽¹⁾
  • For the assessment of cerebral blood flow after carotid revascularization in individuals with severe carotid artery stenosis or signs/symptoms of cerebral hyperperfusion⁽¹⁰⁾

Rationale
Overview
CTP is not widely used especially in outpatients. It is useful in specific scenarios after initial CT and/or MR imaging has been obtained for assessment of, patients with acute stroke, and also a wide range of patients with other cerebrovascular diseases. In evaluating acute stroke it may assist in differentiating the unsalvageable core infarct and salvageable ischemic regions of the brain that may benefit from thrombectomy or thrombolysis.⁽²⁾

Contraindications and Preferred Studies

• Contraindications and reasons why a CT/CTA cannot be performed may include: impaired renal function, significant allergy to IV contrast, pregnancy (depending on trimester).
• Contraindications and reasons why an MRI/MRA cannot be performed may include: impaired renal function, claustrophobia, non-MRI compatible devices (such as non-compatible defibrillator or pacemaker), metallic fragments in a high-risk location, patient exceeds weight limit/dimensions of MRI machine.

Acute Cerebral Ischemia
Cerebral perfusion CT can quantitatively distinguish the extent of irreversibly infarcted brain tissue (infarct core) from the severely ischemic but salvageable tissue (penumbra), providing a basis for the selection of acute stroke patients that are most likely to benefit from thrombolytic treatment⁽²⁾

Cerebral Ischemia and Infarction and Evaluation of Vasospasm after Subarachnoid Hemorrhage (SAH)
CPT can be useful in identifying patients at risk for cerebral ischemia or infarction and for evaluation of vasospasm after subarachnoid hemorrhage. Screening for vasospasm can be performed with TCD US (transcranial doppler ultrasound). CTA, CT perfusion or MRA may be useful in the setting of indeterminate TCD. CT or MR perfusion can help differentiate patients with vascular narrowing but normal perfusion due to the presence of collateral circulation from those without adequate collaterals.

Carotid Artery Stent Placement/Revascularization
Cerebral perfusion CT helps in the assessment of the hemodynamic modifications in patients with severe carotid stenosis. Pre-operatively, CTP may help identify patients at high risk of developing hyperperfusion syndrome after carotid revascularization. Post-operatively CTP provides valuable information in the follow-up of patients after they have undergone carotid revascularization, especially when there is concern for hyperperfusion syndrome.^(1,2)

Temporary Balloon Occlusion (TBO)
Balloon occlusion testing is used prior to a planned endovascular or surgical procedure that will disrupt blood flow to a part of the brain. CTP can be used to detect patients who may not tolerate a prolonged occlusion during a surgery/procedure. Given the length of testing and the need for transport other methods are generally preferred.^(11,12)

Cerebrovascular Reserve
Cerebral perfusion CT, in conjunction with acetazolamide challenge in patients with intracranial vascular stenosis, can evaluate cerebrovascular reserve capacity and help in estimating the potential risk of stroke. It may help to identify candidates for bypass surgery and endovascular treatment to increase cerebral blood flow.^(13,14)

Intracranial Tumors
Cerebral perfusion CT generates permeability measurements in images of brain tumors depicting areas of different blood flow within tumors and the surrounding tissues. This may allow for diagnosis and grading of tumors and may help to monitor treatment.⁽⁵⁾

References

1. Ledbetter LN, Burns J, Shih RY, et al. ACR Appropriateness Criteria® Cerebrovascular Diseases-Aneurysm, Vascular Malformation, and Subarachnoid Hemorrhage. Journal of the American College of Radiology. 2021;18(11):S283-S304. doi:10.1016/j.jacr.2021.08.012
2. American College of Radiology. ACR-ASNR-SPR Practice Parameter For The Performance of Computed Tomography (CT) Perfusion in Neuroradiologic Imaging.; 2022.
3. Mo D, Luo G, Wang B, et al. Staged carotid artery angioplasty and stenting for patients with high-grade carotid stenosis with high risk of developing hyperperfusion injury: a retrospective analysis of 44 cases. Stroke Vasc Neurol. 2016;1(4):147-153. doi:10.1136/svn-2016-000024
4. Yoshie T, Ueda T, Takada T, Nogoshi S, Fukano T, Hasegawa Y. Prediction of cerebral hyperperfusion syndrome after carotid artery stenting by CT perfusion imaging with acetazolamide challenge. Neuroradiology. 2016;58(3):253-259. doi:10.1007/s00234-015-1623-4
5. Jain R. Perfusion CT Imaging of Brain Tumors: An Overview. American Journal of Neuroradiology. 2011;32(9):1570-1577. doi:10.3174/ajnr.A2263
6. Pannell JS, Corey AS, Shih RY, et al. ACR Appropriateness Criteria® Cerebrovascular Diseases-Stroke and Stroke-Related Conditions. Journal of the American College of Radiology. 2024;21(6):S21-S64. doi:10.1016/j.jacr.2024.02.015
7. Simonsen CZ, Leslie-Mazwi TM, Thomalla G. Which Imaging Approach Should Be Used for Stroke of Unknown Time of Onset? Stroke. 2021;52(1):373-380.  doi:10.1161/STROKEAHA.120.032020
8. Wintermark M, Sanelli PC, Albers GW, et al. Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery. American Journal of Neuroradiology. 2013;34(11):E117-E127.  doi:10.3174/ajnr.A3690
9. Guerrero WR, Dababneh H, Eisenschenk S. The role of perfusion CT in identifying stroke mimics in the emergency room: a case of status epilepticus presenting with perfusion CT alterations. Int J Emerg Med. 2012;5(1):4. doi:10.1186/1865-1380-5-4
10. Vasquez RA, Waters MF, Skowlund CJ, Mocco J, Hoh BL. Computed tomographic perfusion imaging of non-hemorrhagic cerebral hyperperfusion syndrome and reversal following medical treatment after carotid artery angioplasty and stenting. J Neurointerv Surg. 2012;4(3):e2-e2. doi:10.1136/jnis.2010.003558
11. Galego O, Nunes C, Morais R, Sargento-Freitas J, Sales F, Machado E. Monitoring Balloon Test Occlusion of the Internal Carotid Artery with Transcranial Doppler. Neuroradiol J. 2014;27(1):115-119. doi:10.15274/NRJ-2014-10014
12. Sorteberg A. Balloon Occlusion Tests and Therapeutic Vessel Occlusions Revisited: When, When Not, and How. American Journal of Neuroradiology. 2014;35(5):862-865. doi:10.3174/ajnr.A3852
13. Vagal AS, Leach JL, Fernandez-Ulloa M, Zuccarello M. The Acetazolamide Challenge: Techniques and Applications in the Evaluation of Chronic Cerebral Ischemia. American Journal of Neuroradiology. 2009;30(5):876-884. doi:10.3174/ajnr.A1538
14. You SH, Jo SM, Kim YJ, Lee JH, Jo KD, Park WS. Pre- and Post-Angioplasty Perfusion CT with Acetazolamide Challenge in Patients with Unilateral Cerebrovascular Stenotic Disease. J Korean Neurosurg Soc. 2013;54(4):280. doi:10.3340/jkns.2013.54.4.28

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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