Brain Single-Photon Emission CT With HMPAO and Safety of Thrombolytic Therapy in Acute Ischemic Stroke Proceedings of the Meeting of the SPECT Safe Thrombolysis Study Collaborators and the Members of the Brain Imaging Council of the Society of Nuclear Medicine Stroke. 1997;28:

BACKGROUD To reliably identify patients at risk for symptomatic hemorrhagic transformation (SHT), future trials of thrombolysis for acute ischemic stroke might use a vascular imaging protocol applicable to a multicenter setting. The goal of this commentary is to address the safety of intravenous thrombolysis with the recombinant tissue plasminogen activator (rTPA) and potential solutions offered by single-photon emission CT (SPECT) as a noninvasive brain perfusion imaging modality.

INTRODUCTION In clinical studies, IV thrombolysis with the rTPA was shown to be significantly better than placebo in improving clinical outcome at 3 months. Symptomatic intracerebral hemorrhages were 10 times more likely among treated patients than control subjects.

INTRODUCTION CT are not specific enough SPECT imaging may prove very helpful to screen out from treatment those patients at increased risk for developing intracerebral hemorrhage On July 29 through 30, 1996, the SPECT Safe Thrombolysis Study collaborators and the members of the Brain Imaging Council of the Society of Nuclear Medicine met in Houston, Tex, to discuss the potential of nuclear medicine technology to assist in clinical decision making attendant to thrombolysis in the acute stroke setting

INTRODUCTION (1) safety of intravenous thrombolysis during the first 6 hours of stroke onset; (2) clinical and CT findings in patients with hemorrhagic transformation; (3) experience with HMPAO-SPECT in acute stroke and thrombolysis; (4) feasibility of brain SPECT with HMPAO for triage of acute stroke patients; (5) imaging properties of HMPAO particular to cerebral ischemia; (6) visual and semiquantitative analysis of brain SPECT scans; (7) requirements for quality control and a central imaging laboratory; and (8) implementation of SPECT technology through clinical trials in acute ischemic stroke.

Safety of Intravenous Thrombolysis During the First 6 Hours of Stroke Onset In 1996, intravenous thrombolysis with rTPA was approved by the Food and Drug Administration (FDA) as the "first-ever" effective treatment for ischemic stroke during the first 3 hours after symptom onset. Mortality was 21% in the placebo-treated patients and 17% in those treated with rTPA

Safety of Intravenous Thrombolysis During the First 6 Hours of Stroke Onset The incidence of fatal bleeding in the rTPA group of the NINDS-rt-PA Stroke Trial was 2.9% compared with 0.3% in the placebo group, while the incidence of symptomatic bleeding was 6.4% compared with 0.6% at 36 hours after stroke onset even if rTPA is administered within the first 3 hours, intravenous thrombolysis is associated with an increased incidence of SHT

Clinical and CT Findings in Patients With Hemorrhagic Transformation SHT occurred most often when CT scans showed hypodensity in more than one third of the middle cerebral artery territory early ischemic changes on CT during the first 6 hours are not helpful in predicting SHT SHT can still occur after rTPA therapy even when the CT does not show any hypodensity, and not every patient with early CT changes will bleed if given rTPA.

Clinical and CT Findings in Patients With Hemorrhagic Transformation Only early CT findings of infarction (edema, hypodensity, midline shift) and NIHSS scores >20 were significantly associated with an increased risk of SHT The risk of SHT:advanced age (ie, greater than 77 years), patients with hypertension >185/110 mm Hg,but CT and clinical data alone are not precise measures of tissue viability or risk of SHT

Experience With HMPAO-SPECT in Acute Stroke and Thrombolysis Experience With HMPAO-SPECT in Acute Stroke and Thrombolysis patients at risk of hemorrhagic transformation, brain edema, and death had markedly decreased brain perfusion, usually less than 40%, compared with the nonaffected side, while those who recovered spontaneously had minimal or no decrease in brain perfusion on HMPAO-SPECT PPV was 36% for hemorrhagic transformation of the severe neurological impairment on admission (Canadian Neurological Scale scores <5), 55% for early signs of ischemia on noncontrast CT, and 73% for HMPAO-SPECT.

Experience With HMPAO-SPECT in Acute Stroke and Thrombolysis Experience With HMPAO-SPECT in Acute Stroke and Thrombolysis The study by Ueda et al demonstrated that an ischemic region-to-cerebellar ratio 1.5 were seen in all patients who developed hemorrhagic transformation

Feasibility of Brain SPECT With HMPAO for Triage of Acute Stroke Patients Discussion of how long for preparing HMPAO Since "time is brain," SPECT scanning should not delay rTPA therapy. If pretreatment scanning is not feasible, SPECT can be postponed until after initiation of rTPA infusion because of the excellent retention properties of HMPAO

Imaging Properties of HMPAO Particular to Cerebral Ischemia Imaging Properties of HMPAO Particular to Cerebral Ischemia HMPAO dose is distributed within 2 minutes in proportion to the regional cerebral blood flow The retention mechanism of HMPAO in brain tissue involves a chemical interaction with intracellular glutathione the luxury perfusion syndrome during the subacute phase of stroke may produce increased uptake of the tracer

Visual and Semiquantitative Analysis of Brain SPECT Scans A more detailed SPECT stroke scale is proposed here that allows visual and/or computer-assisted assessment of the severity, extent, and location of the ischemic lesion as follows: (1) The severity of ischemia can be described as mild (<20% difference between homologous ROI or high and mixed visual patterns), moderate (21%to 90% ROI, low pattern), or severe (91% to 100% ROI,focal absence of brain perfusion23 ).

Visual and Semiquantitative Analysis of Brain SPECT Scans (2) The extent of the ischemic lesion is described by the number ofregions affected (frontal, parietal, temporal,occipital, and basal ganglia/internal capsule). A lesion that exceeds one third of the middle cerebral artery territory will occupy two or more regions. (3)The location of the ischemic lesion indicates whether the perfusion defect involves cortical or subcortical structures or both.

Requirement for Quality control and a Central Imaging Laboratory

Implementation of SPECT Through Clinical Trials in Acute Ischemic Stroke Providing clinicians with an easy-to-use strategy to identify patients at risk for treatment complication Requiring the close cooperation of neurologists and nuclear medicine physicians