Stroke is a common and serious disorder, with an incidence of ≈795 000 each year in the United States alone. Worldwide, stroke is a leading cause of death and disability. Recombinant tissue plasminogen activator (rtPA) was approved a decade ago for the treatment of acute ischemic stroke. The guidelines for its use include stroke onset within 3 hours of intravenous drug administration, preceded by a computed tomographic (CT) scan to exclude the presence of hemorrhage, which is a contraindication to the use of the drug. Although randomized, controlled studies in Europe and North America demonstrated the efficacy of this treatment, it also was associated with an incidence of intracranial hemorrhage of 6.4%,1,2⇓ which was shown on subsequent studies to be even greater if there was not strict adherence to the administration protocol.3 The goal of these controlled studies was to evaluate patient outcome. There was no attempt to determine the site, or even the actual presence, of a vascular occlusion, the degree of tissue injury, or the amount of tissue at risk for further injury that might be salvageable.

More than a decade later, progress for treating acute ischemic stroke has been slow,4,5⇓ yet the goals for treating this common disease have expanded. First, there is the need to extend the therapeutic window from 3 to ≥6 hours. Even with the rapid communication and transportation in our societies today, very few patients present for treatment within 3 hours.6 Second, there is the desire to improve the efficacy of treatment. It had been shown even before the randomized, controlled studies that intravenous rtPA works better in small peripheral vessels than in the large vessels at the skull base.7 Third, there is a need to decrease the complication rate, especially if patients are to be …

Recommendations for imaging of acute ischemic stroke: A scientific statement from the American Heart Association

A number of techniques have been developed during the past four decades to evaluate cerebral perfusion. The oldest used 133Xe, a lipophilic radioactive tracer that easily diffuses through the blood-brain barrier (BBB). It was either injected or inhaled, and probes placed over the scalp were used to measure perfusion to the cerebral cortex.1,2 In the mid-1970s, the development of a scanner to detect the emission of positrons led to positron emission tomography (PET) in humans.3 Using a number of radioisotopes, this technology can measure cerebral blood flow (CBF) and various metabolic processes, but until recently it has been primarily used as a research tool. Stable (“cold”) xenon was found to attenuate x-rays in a manner similar to iodine, and there were a number of projects in the 1970s to use this gas as a contrast agent for the rapidly emerging technology of computed tomography (CT), particularly as a perfusion tracer.4 This resulted in the development of the xenon-enhanced CT (XeCT) technique to calculate CBF in patients.5 With improvements in single photon emission CT (SPECT) during the 1980s, a number of compounds that are metabolized in the central nervous system (CNS) were found to be appropriate for perfusion imaging.6,7 Perfusion-weighted and diffusion-weighted magnetic resonance (MR) imaging (PWI and DWI) were developed in the late 1980s,8,9 and that technology has continued to improve. Finally, with the evolution of helical and spiral multislice CT technology, CT perfusion (CTP) imaging is becoming a potentially important clinical technique.10

Although the development of these technologies has been fascinating, their role in evaluating a variety of diseases of the CNS is controversial. It might seem obvious that a disorder of blood flow, such as acute stroke or chronic vascular occlusive disease, should be studied with a perfusion imaging technique. …

Guidelines and Recommendations for Perfusion Imaging in Cerebral Ischemia: A Scientific Statement for Healthcare Professionals by the Writing Group on Perfusion Imaging, From the Council on Cardiovascular Radiology of the American Heart Association

Background and Purpose—We have developed a dynamic CT method to measure absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). In this study we evaluated the ability of CT-derived functional maps to detect infarction in a rabbit model of focal cerebral ischemia. Methods—Sequential dynamic CT studies were performed at 2 different slices in 5 control rabbits and another 8 after induction of focal cerebral ischemia. The size of critically ischemic tissue was correlated to size of infarction measured by postmortem 2,3,5-triphenyltetrazolium chloride staining. In the control rabbits, short-term variability of the parameters was assessed by ANOVA analysis. Results—In 7 of 8 animals of the ischemia group, cerebral infarction was visible on 2,3,5-triphenyltetrazolium chloride staining, constituting 16.7±10.6% of the ipsilateral hemisphere. Good agreement of CBF functional maps with tissue specimens was found with respect to size and location of infarction. Best prediction of...

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.32.1.175

Perfusion Mapping Using Computed Tomography Allows Accurate Prediction of Cerebral Infarction in Experimental Brain Ischemia

The invention provides, in a general sense, a new labeling strategy employing 99m Tc chelated with ethylenedicysteine (EC). EC is conjugated with a variety of ligands and chelated to 99m Tc for use as an imaging agent for tissue-specific diseases. The drug conjugates of the invention may also be used as a prognostic tool or as a tool to deliver therapeutics to specific sites within a mammalian body. Kits for use in tissue-specific disease imaging are also provided.

Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging

The aim of this study was to define the accuracy of 99mTc-ethyl cysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT) in distinguishing transient ischemic attack from completed ischemic stroke at early stages after the onset of symptoms. In a prospective study we examined 82 patients within 6 hours after the onset of symptoms (neurologic deficit caused by middle cerebral artery ischemia) using both 99mTc-ECD-SPECT and computed tomography (CT). The follow-up was based on Scandinavian Stroke Scale (SSS) 24 hours and 5–7 days, as well as on CT 7 days, after the event. SPECT evaluation was performed both visually and using semiquantitative region-of-interest (ROI) analysis. According to visual SPECT analysis, on admission 59 of 82 patients had activity deficits in the symptomatic hemisphere. After 7 days, all these patients had neurologic symptoms (SSS 28 ± 12 points), caused by a cerebral infarction as evidenced with CT. Twenty-three of 82 patients displayed no early activity deficit ...

https://journals.sagepub.com/doi/pdf/10.1097/00004647-199808000-00013

Differentiation Between Transient Ischemic Attack and Ischemic Stroke Within the First Six Hours After Onset of Symptoms by Using 99mTc-ECD-SPECT

Single-photon emission tomography (SPET) is widely used in the investigation of acute stroke. We investigated the relationship between SPET data and functional outcome in a large group of acute stroke patients. One hundred and eight patients underwent cerebral computed tomography (CT) and technetium-99m hexamethylpropylene amine oxime SPET after acute ischaemic stroke. We categorised the clinical presentation according to the Oxford classification of acute stroke. Outcome was measured 1 year after stroke using mortality and the Barthel Index for survivors. SPET scans were interpreted without reference to the clinical data using a semi-automatic technique. Three experienced observers determined the presence of luxury perfusion using suitably scaled SPET images in conjunction with the CT scan. Both SPET volume and severity of deficit were significantly negatively correlated with Barthel Index at 1 year (rs=−0.310,P<0.0001, andrs=−0.316,P<0.0001 respectively). In patients scanned with SPET within 16 h of stroke onset, the correlations were more strongly negative (rs=−0.606,P<0.0001, andrs=−0.492,P<0.005 respectively). Luxury perfusion was not associated (χ2=0.073,df=1,P=0.79) with good functional outcome (Barthel score ≥60). Stepwise logistic regression identified Oxford classification, total deficit volume and patient's age as significant predictors of functional outcome. Overall predictive accuracy was 72%. Predictive accuracy was better in patients who received SPET within 16 h of stroke onset. SPET provides useful information about the functional outcome of acute stroke at 1 year. However, the accuracy of prediction decreases the longer SPET is delayed. Prognostication using SPET in combination with clinical assessment and other investigations may also be considered.

Prognostic value of single-photon emission tomography in acute ischaemic stroke.

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Prognostic value of single-photon emission tomography in acute ischaemic stroke.