Neuroimaging Paradigms to Identify Patients for Reperfusion Therapy in Stroke of Unknown Onset

Abstract

Despite the proven efficacy of intravenous alteplase or endovascular thrombectomy for the treatment of patients with acute ischemic stroke, only a minority receive these treatments. This low treatment rate is due in large part to delay in hospital arrival or uncertainty as to the exact time of onset of ischemic stroke, which renders patients outside the current guideline-recommended window of eligibility for receiving these therapeutics. However, recent pivotal clinical trials of late-window thrombectomy now force us to rethink the value of a simplistic chronological formulation that “time is brain.” We must recognize a more nuanced concept that the rate of tissue death as a function of time is not invariant, that still salvageable tissue at risk of infarction may be present up to 24 h after last-known well, and that those patients may strongly benefit from reperfusion. Multiple studies have sought to address this clinical dilemma using neuroimaging methods to identify a radiographic time-stamp of stroke onset or evidence of salvageable ischemic tissue and thereby increase the number of patients eligible for reperfusion therapies. In this review, we provide a critical analysis of the current state of neuroimaging techniques to select patients with unwitnessed stroke for revascularization therapies and speculate on the future direction of this clinically relevant area of stroke research.

A Comparison of T2 Relaxation-Based MRI Stroke Timing Methods in Hyperacute Ischemic Stroke Patients: A Pilot Study

“…The ability of the FLAIR ratio and the DWI/FLAIR mismatch approach was comparatively weak, which is in accordance with previous studies that have reported low sensitivity of FLAIR-based methods. 8,49,50 The changes in T 2 relaxation that occur during early ischemia reflect the radical changes in water dynamics caused by anoxic depolarization, whereby water is shifted from the extracellular to intracellular compartment, ie, cytotoxic edema, followed by the time-dependent breakdown of intracellular macromolecules. 51 The same pathophysiological factors (cytotoxic edema with the breakdown of intracellular macromolecules) that cause changes in T 2 relaxation, therefore, also contribute to the signal of images with a T 2 w component.…”

“…The potential utility of FLAIR imaging for estimating onset time has received considerable attention within the stroke imaging literature (see Etherton et al 8 for review) but has only recently been directly compared with the T 2 relaxation time. 16 Results by Duchaussoy et al 16 and from our study suggest that the T 2 relaxation time will provide a more accurate estimation of stroke onset time than FLAIR-based approaches.…”

Acute Stroke

“…[30][31][32][33] MRI could also be used to estimate IS duration in patients presenting with unclear symptom onset. 34 The presence of a DWI-FLAIR (fluid attenuated inversion recovery) mismatch (DWI-positive lesion without a corresponding hyperintense signal in FLAIR sequences) suggests the presence of IS with onset within 4.5 hours. 35 Although ultrarapid (<10 minutes) stroke MRI protocols are becoming increasingly available, it remains to be determined whether direct access to MRI in all stroke patients is costeffective.…”

“…38,39 However, advanced neuroimaging techniques such as CT perfusion (CTP) or MR perfusion (MRP) can estimate the time of onset and quantify the extent of irreversible damage (ischemic core) and the volume of potentially salvageable hypoperfused brain tissue (ischemic penumbra). 34,40 Patients with a large core-penumbra mismatch may be selected for reperfusion treatment beyond conventional time windows (4.5 hours for IVT and 6 hours for EVT). Perfusion studies can acquire several parameters such as cerebral blood volume and flow (CBV and CBF), mean transit time (MTT), and time to peak enhancement.…”

Leukoaraiosis May Confound the Interpretation of CT Perfusion in Patients Treated with Mechanical Thrombectomy for Acute Ischemic Stroke

“…T he main utility of perfusion images obtained from patients with acute ischemic stroke is the identification and quantifi-cation of areas of nonviable tissue (NVT) and areas of ischemic penumbra that represent hypoperfused but still salvageable tissue. 1,2 These focal alterations in patients eligible for acute stroke therapies can be evaluated by dynamic contrast-enhanced CT and MR imaging acquisitions, 3,4 the former being the most commonly used technique worldwide for the assessment of cerebral perfusion in patients with acute stroke. 5 However, a great variability exists not only in image acquisition and postprocessing techniques but also in intrinsic features of cerebral perfusion.…”