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Edwards et al. Vessel Plus 2021;5:42 https://dx.doi.org/10.20517/2574-1209.2021.18 Page 9 of 14

with metal foreign bodies such as pacemakers. CTP does not face these challenges. Additionally, MRI within
[70]
24-48 h of symptoms has been reported to miss as many of 12%-20% of PCS [66-69] . Choi et al. demonstrated
in a cohort of PCS presenting with vertigo or dizziness and DWI MRI confirmed stroke, that 4% had a
negative early DWI MRI when performed within 48 h. However, when perfusion imaging (CT or MRI) was
added to clinical assessment (Head impulse, nystagmus, test of skew, plus acute hearing loss detected by
[70]
finger rubbing), 100% of these early strokes missed on MRI were detected .
PCS due to acute basilar artery occlusion is associated with a high rate of death and disability . The
[71]
optimal treatment pathway for this condition has not been established [71,72] . Even in the era of endovascular
thrombectomy, the rate of good functional outcome remains at ~30% . The Posterior circulation Alberta
[73]
stroke program early CT score (pc-ASPECTS) has been used to predict outcome after vertebrobasilar
[74]
stroke . Studies have demonstrated improved detection of ischaemic lesions when using CTP compared to
CTA-SI alone for assessment of pc-ASPECTS [61,75] . Furthermore, CTP-based assessment demonstrated
[75]
substantially better inter-rater agreement and was predictive of functional outcome . This ability to
accurately identify lesions and predict outcome may help to guide therapy.

PCS perfusion abnormalities vary considerably depending on the site of vascular occlusion [Figure 4A-F].
The size and distribution of the perfusion lesion are influenced by the involvement of different posterior
circulation vessels including the basilar, vertebral, cerebellar or posterior cerebral arteries. It has been well
established that CTP is less sensitive in detection of small volume infarcts than DWI . Multiple studies
[76]
have confirmed the factors associated with reduced sensitivity of PCS detection include small stroke volume
[15]
and location outside of the cerebellum or posterior cerebral artery territory . Small brainstem strokes are
[56]
not well visualised. Despite this lower sensitivity, NCCT alone is even less sensitive in detecting PCS . A
[77]
[14]
study by Ostman et al. demonstrated that compared to non-enhanced CT, CTP improved sensitivity in
detecting cerebellar lesions from 12% to 52%. This difference was even more pronounced in cerebellar
lesions greater than 5 mL with sensitivity increasing from 32% to 91%.
Among the perfusion parameters, MTT [57,61] , TTD and TTP have been most frequently reported as
[57]
[56]
sensitive markers of PCS. Similarly, CBV has been shown to be a specific marker of PCS ischaemia [56,57] . To
date, there have been no studies characterising the optimal perfusion threshold for ischaemic core and
penumbra volume in PCS. Current proprietary automated core and penumbra maps are based on
thresholds derived from anterior circulation stroke [17,32,34,38,41,44] . As such, caution should be applied to
automated estimates of core and penumbra in PCS until these thresholds are validated. It is prudent for
clinicians to inspect the raw perfusion maps as lesions may be apparent at subthreshold levels [Figure 1I-K,
Figure 2I-L].

Future directions
CTP has been integral to studies of acute therapies over the extended time window [3,4,6,7] . Ma et al. used
[4]
CTP-based criteria to select patients who benefit from thrombolysis up to 9 h after stroke onset. Further
randomised control trials are underway exploring even later window thrombolysis utilising CTP-based
selection criteria [Tenecteplase in Stroke Patients Between 4.5 and 24 h (TIMELESS), NCT03785678 and
Extending the time window for Tenecteplase by Effective Reperfusion of peNumbrAL tissue in patients with
Large Vessel Occlusion (ETERNAL), NCT04454788]. Unfortunately, these studies have been limited to
patients with acute hemispheric infarction. Given the promising diagnostic applications of CTP for PCS,
future trials of acute therapy using CTP based selection may be warranted.