In this issue of the AJNR News Digest, we highlight considerations regarding the use of CT perfusion (CTP) imaging for acute neurovascular assessment.

Although the idea of measuring cerebral perfusion by tracking a contrast bolus with rapid sequence imaging has been around since the earliest days of CT, in the mid/late 1970s,¹ it was not until two decades later that multidetector row CT acquisition and postprocessing technology became sufficiently rapid such that CTP could finally be implemented as a routine, practical tool for the assessment of hyperacute stroke.² With proper scan parameters on modern CT systems, wide z-axis CTP coverage can be obtained at acceptably low radiation doses.³

Only in the past year, however, has a potential role for CTP in patient selection for IV and intra-arterial (IA) stroke treatments been definitively suggested by randomized prospective data from the MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, and REVASCAT trials.⁴  Despite this new research—because these trials were designed to test if IAT is effective, rather than if CTP is optimally efficient—and despite continued improvements in CTP’s speed, radiation dose, and image noise over the past 15+ years, the appropriate role of CTP in stroke triage remains both unproven and controversial.⁴

The AJNR articles selected for this issue of the Digest, therefore, were chosen because they reflect important issues impacting the acquisition, postprocessing, interpretation, accuracy, and role of CTP in patients with acute neurologic disorders.

Three of these papers address technical hazards resulting from the lack of standardization and validation with current CTP acquisition and postprocessing protocols.  In “Exposing Hidden Truncation-Related Errors in Acute Stroke Perfusion Imaging”, Copen et al (AJNR 2015;36:638–45) highlight the pitfall of overestimating ischemic lesion volumes when scan acquisition times are insufficient for iodinated contrast to fully circulate via collaterals through the entire, hypoperfused tissue bed. The importance of contrast bolus timing is also underscored in the paper “Timing-Invariant CT Angiography Derived from CT Perfusion Imaging in Acute Stroke: A Diagnostic Performance Study” by Smit et al (AJNR 2015;36:1834–38).

CTP thresholds for quantification of critically ischemic tissue volumes (ie, “infarct core”) vary not only with the postprocessing platform used, but also with regional anatomy.^5,6  In “Toward Patient-Tailored Perfusion Thresholds for Prediction of Stroke Outcome” Eilaghi and Aviv et al (AJNR 2014;35:472–77) discuss the potential marked variability (and hence, limited reliability) of cerebral blood flow/volume thresholds in differing individual patients.

The reliability of CTP for the detection and delineation of both large and small ischemic lesions (ie, lacunar infarcts) is limited by the image noise intrinsic to CT scanning (attributable, in part, to the low signal-to-noise ratios of iodinated contrast in even normally perfused brain tissue capillaries, compared with the high signal typical with MRI).⁷  Indeed,

although Das and Aviv et al showed nominal CTP detection of cortical lacunar infarcts in “Multimodal CT Provides Improved Performance for Lacunar Infarct Detection” (AJNR 2015;36:1069–75), detection of more prevalent deep lacunar infarcts was poor.

The recent IAT trials that used CTP for patient selection showed excellent outcomes in the treated groups, but at the price of excluding many patients who might have derived some benefit from treatment.⁴  Alternative selection strategies, including MRI-based algorithms, that result in a higher proportion of screened patients being treated are being considered.⁸ Whether CTP is optimal for efficient treatment selection is currently under study.  In “Clinical Stroke Penumbra: Use of National Institutes of Health Stroke Scale as a Surrogate for CT Perfusion in Patient Triage for Intra-Arterial Middle Cerebral Artery Stroke Therapy,” Boxerman et al (AJNR 2012;33:1893–900) suggest that, in some settings (normal-appearing unenhanced head CTs at very early times post-ictus comes to mind), clinical exam plus CTA might be sufficient to make a treatment decision.

What, then, are recognized indications for CTP, given its not-yet-established role in IV and IA treatment selection? Certainly, CTP provides valuable differential diagnostic assessment of potential stroke mimics when MRI is contraindicated or unavailable. CTP also provides useful prognostic information, not only with regard to IV treatment outcomes (McDonald et al, "Pretreatment Advanced Imaging in Patients with Stroke Treated with IV Thrombolysis: Evaluation of a Multihospital Data Base", AJNR 2014;35:478–81), but also with regard to the likelihood of reperfusion (Horsch et al, for the Dutch Acute Stroke Study Investigators, "Predictors of Reperfusion in Patients with Acute Ischemic Stroke," AJNR 2015;36:1056–62). Finally, Sanelli et al note the “Cost-Effectiveness of CT Angiography and Perfusion Imaging for Delayed Cerebral Ischemia and Vasospasm in Aneurysmal Subarachnoid Hemorrhage” (AJNR 2014;35:1714–20)—a CTP application in use at many centers.

If you are interested in this topic you may want to read these other articles:

1. Axel L. Cerebral blood flow determination by rapid-sequence computed tomography. Radiology 1980;137:679–86, 10.1148/radiology.137.3.7003648
2. Hunter GJ, Hamberg LM, Ponzo JA, et al. Assessment of cerebral perfusion and arterial anatomy in hyperacute stroke with 3-D functional CT: early clinical results. AJNR Am J Neuroradiol 1998;19:29–37
3. Wintermark M, Lev MH. FDA investigates the safety of brain perfusion CT. AJNR Am J Neuroradiol 2010;31:2–3, 10.3174/ajnr.A1967
4. Liebeskind DS, Parsons MW, Wintermark M, et al. Computed tomography perfusion in acute ischemic stroke: is it ready for prime time? Stroke 2015;46:2364–67, 10.1161/STROKEAHA.115.009179
5. Kamalian S, Kamalian S, Maas MB, et al. CT cerebral blood flow maps optimally correlate with admission diffusion-weighted imaging in acute stroke but thresholds vary by post-processing platform. Stroke 2011;42:1923–38, 10.1161/STROKEAHA.110.610618
6. Payabvash S, Souza L, Wang Y, et al. Regional ischemic vulnerability of the brain to hypoperfusion: the need for location specific computed tomography perfusion thresholds in acute stroke patients. Stroke 2011;42:1255–60, 10.1161/STROKEAHA.110.600940
7. Schaefer PW, Souza L, Kamalian S, et al. Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke. Stroke 2015;46:419–24, 10.1161/STROKEAHA.114.007117
8. Leslie-Mazwi TM, Hirsch JA, Falcone GJ, et al. Endovascular stroke treatment outcomes after patient selection based on MRI and clinical criteria. JAMA Neurol 2016;73:43–49, 10.1001/jamaneurol.2015.3000

 

Image modified from: Horsch AD, Dankbaar DW, Niesten JM, et al. Predictors of reperfusion in patients with acute ischemic stroke.