LCD L38667: Computed Tomography Cerebral Perfusion Analysis (CTP)

CTP (using automated post-processing software algorithmic analysis) is medically reasonable and necessary in patients with small acute ischemic stroke (AIS) caused by a unilateral large vessel occlusion (LVO) in the proximal anterior circulation evaluated at stroke centers; CTP can be used to aid in selection for endovascular mechanical thrombectomy (EVT) if one of the following other conditions is fulfilled:

• Treatment (femoral puncture) can be started within 6-24 hours of the time last known to be at neurologic baseline and who meet the pre-CTP inclusion/exclusion criteria* as defined by the DAWN trial (1), or

• Treatment (femoral puncture) can be started within 6-16 hours of the time last known to be at neurologic baseline and who meet the pre-CTP inclusion/exclusion criteria* as defined by the DEFUSE 3 trial (2)

*excluding criteria purely related to study mechanics (e.g., able to return for protocol required follow-up visits, etc.).

Noncontrast CT (NCCT) is the mainstay for initial AIS imaging due to widespread availability, rapid scan times, and detection of intracranial hemorrhage (which leads to very different management from infarction). Multimodal CT includes NCCT, CT angiography (CTA) (to assess site of vascular occlusion), and CT Perfusion Imaging (CTP). CTP consists of a temporal sequence of head CT scans obtained during the wash-in and wash-out of an IV bolus of iodinated contrast agent. Post-acquisition data analysis by dedicated software allows creation of multiple hemodynamic parametric maps (based on contrast time-density curves) for clinical interpretation. Hemodynamic parameters include time to maximum contrast intensity (Tmax), mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV), mathematically related by the equation CBF = CBV/MTT (3). These maps are able to estimate brain regions with high probability of irreversible infarction (ischemic core) versus areas of potentially reversible ischemia (penumbra). Both core and penumbra are estimates of probabilistic tissue fate. While CTP has been studied in acute ischemic stroke for decades (4), only recently was it found likely to influence treatment decision (5). Subsequently, two level I randomized controlled trials (RCTs) (DAWN and DEFUSE 3) found CTP helped determine eligibility for EVT in the late time period (6-24 hr.) of an acute ( The DAWN trial (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) studied whether patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late EVT (1). See table for key inclusion criteria. Patients were randomly assigned to EVT plus standard medical management (MM) (N=107, mean age 69.4 yr.) or to MM alone (N=99, mean age 70.7 yr.). Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (moderate to severe stroke) for both groups. The trial was stopped for efficacy at the first interim analysis. At 90 days, the rate of functional independence, as defined by a score of 0-2 on the modified Rankin scale (mRS) of 0-6, was greater for EVT than MM (49% versus 13%; adjusted difference, 33%; 95% CI, 21–44; posterior probability of superiority >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the EVT group and 3% in the MM group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00).

Key Inclusion Criteria for DAWN and DIFUSE 3

Parameter

DAWN