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(Stroke. 1997;28:1830-1834.)
© 1997 American Heart Association, Inc.

Articles

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

Andrei V. Alexandrov, MD; Joseph C. Masdeu, MD; Michael D. Devous, Sr, PhD; Sandra E. Black, MD, FRCP(C); James C. Grotta, MD

From the University of Texas at Houston (A.V.A., J.C.G.), New York (NY) Medical College (J.C.M.), the University of Texas at Dallas (M.D.D.), and the University of Toronto (Canada) (S.E.B., A.V.A.).

Correspondence to Dr Andrei Alexandrov, Stroke Program, University of Texas at Houston, MSB 7.044, 6431 Fannin St, Houston, TX 77030. E-mail avalexandrov{at}worldnet.att.net

	Abstract

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
Background 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.

Summary of Review Even if patients with severe stroke, extensive ischemic changes on CT scan, advanced age, and high blood pressure are excluded from thrombolytic therapy, this cannot completely guarantee the safety of using rTPA. Brain SPECT scanning with hexamethylpropyleneamine oxime (HMPAO) may help to screen out patients at risk if performed in addition to clinical and CT tests. The knowledge of pretreatment severity, extent, and location of ischemia might identify good versus poor responders to rTPA therapy. HMPAO-SPECT is widely available and feasible to perform without delaying rTPA therapy. Rigorous quality control and use of reproducible visual and semiquantitative methods of interpreting SPECT are necessary for implementation of SPECT technology in multicenter clinical trials.

Conclusions The major obstacle to general acceptance of thrombolytic therapies and rTPA in particular is the fear of symptomatic hemorrhagic transformation, and because HMPAO-SPECT might reliably identify patients at high risk of symptomatic hemorrhagic transformation, the clinical value of HMPAO-SPECT in patient selection for thrombolysis during the first hours of acute ischemic stroke should be determined through a prospective clinical trial.

Key Words: tissue plasminogen • thrombolytic therapy • tomography, emission computed

	Introduction

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
One highlight of the Decade of Brain is the development of the first effective therapy for acute ischemic stroke. In two controlled clinical studies, intravenous thrombolysis with the rTPA was shown to be significantly better than placebo in improving clinical outcome at 3 months.¹ However, symptomatic intracerebral hemorrhages were 10 times more likely among treated patients than control subjects. Patients more likely to bleed might be identifiable, but currently used clinical and imaging tools (CT) are not specific enough, as is evident from published data.¹ SPECT imaging may prove very helpful to screen out from treatment those patients at increased risk for developing intracerebral hemorrhage. To determine the usefulness of SPECT imaging, studies would need to be performed in a subset of patients in ongoing or future thrombolytic clinical trials. A standardized vascular imaging protocol applicable to a multicenter setting would have to be developed for such a study. This report and the meeting on which it is based represent initial steps forward in developing such a protocol for thrombolytic therapies.

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. The following issues were reviewed: (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. This article represents the views of the meeting participants; it is based on the transcripts of the entire meeting and was reviewed by all participants (see "Appendix").

	Safety of Intravenous Thrombolysis During the First 6 Hours of Stroke Onset

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
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. Approval was based on the positive results of the rTPA Stroke Trial sponsored by the NINDS.¹ In the placebo group, 20% of patients who came into the emergency room within 3 hours of a stroke recovered with minimal or no deficit by 3 months (scores of 0 to 1 with the NIHSS). Of the patients randomized to rTPA, 31% achieved the same favorable outcome, and this benefit was not at the expense of a greater mortality. Mortality was 21% in the placebo-treated patients and 17% in those treated with rTPA.¹

However, despite that positive outcome, a substantial number of patients had SHT. SHT was determined by worsening of the neurological deficit by 2 points or greater using the NIHSS and follow-up CT scans.¹ 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.¹ Therefore, even if rTPA is administered within the first 3 hours, intravenous thrombolysis is associated with an increased incidence of SHT. Clearly, if patients likely to bleed can be reliably identified and excluded from further trials or thrombolytic treatment, then the safety profile and outcome from rTPA therapy could be optimized.

In other recently completed thrombolytic trials,^{2 3 4 5} the rates of SHT were even greater. However, there were substantial differences between these trials and the NINDS rTPA Stroke Trial. For example, the studies were different in terms of the time window (ie, up to 6 hours after stroke onset), rTPA dosages, the number of protocol violations, the absence of a standardized blood pressure management protocol, and the use of other thrombolytic agents such as streptokinase together with aspirin or heparin. Although these differences make meta-analysis logistically difficult, the greater rates of SHT observed in these trials point to the safety of thrombolysis as the key concern in clinical decision making.

	Clinical and CT Findings in Patients With Hemorrhagic Transformation

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
An important result that emerged from the European Cooperative Acute Stroke Study (ECASS)² is that SHT occurred most often when CT scans showed hypodensity in more than one third of the middle cerebral artery territory (R. von Kummer, personal communication, 1996). However, early ischemic changes on CT were not quantified in the NINDS study. More importantly, SHT can still occur after rTPA therapy even when the baseline CT does not show any hypodensity, and conversely not every patient with early CT changes will bleed if given rTPA. Furthermore, if asymptomatic small petechial hemorrhages on outcome scans are excluded as clinically irrelevant, early ischemic changes on CT during the first 6 hours are not helpful in predicting SHT in a series of consecutive patients.⁶

After completion of the NINDS trial, the predictive values of several clinical and imaging criteria were evaluated using logistic regression analysis.⁷ Only early CT findings of infarction (edema, hypodensity, midline shift) and NIHSS scores >20 were significantly associated with an increased risk of SHT (odds ratios [95% CI] were 7.8 [2.2 to 27] for CT and 11 [2.1 to 59] for NIHSS).⁷ Although advanced age (ie, greater than 77 years) may also potentiate the risk of SHT, there was no significant association independent of stroke severity and CT findings.⁷ However, patients still benefit from rTPA in these high-risk groups, and these variables cannot predict who should not be treated. Moreover, the exact threshold of CT abnormality that is sufficient to disqualify a patient from receiving thrombolytic therapy or make the therapy ineffective and potentially more dangerous is not really known.

Diastolic blood pressure also correlates with the rate of SHT⁸ but was not shown to be a specific marker of patients at risk in the NINDS study.⁷ Although patients with hypertension >185/110 mm Hg were excluded and a rigorous posttreatment blood pressure management protocol was implemented in the NINDS trial, the rate of SHT was still significantly greater in the rTPA group than in the control group.¹ Therefore, CT and clinical data alone are not precise measures of tissue viability or risk of SHT and should be supplemented with some form of vascular imaging to identify patients at risk of complications from thrombolysis.⁹ SPECT is a widely available method that may be suitable for this purpose.^{10 11 12}

	Experience With HMPAO-SPECT in Acute Stroke and Thrombolysis

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
Studies in several series of consecutive stroke patients consistently showed that 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.^{13 14 15 16 17 18 19 20 21 22 23} Moreover, focal absence of brain perfusion as determined by visual analysis of HMPAO-SPECT scans during the first 24 hours after stroke onset can be predictive of the risk of hemorrhagic transformation occurring spontaneously or during anticoagulant therapy.¹⁴ In this study of 85 consecutive stroke patients, the neurological deficit scores and CT scans were obtained within 6 hours and HMPAO-SPECT at a median time of 24 hours after stroke onset. No patients had hemorrhagic infarct on admission, and 13 symptomatic and asymptomatic hemorrhagic transformations were found on days 3 through 5. Positive predictive value was 36% (95% CI, 26 to 46) for hemorrhagic transformation of the severe neurological impairment on admission (Canadian Neurological Scale scores <5), 55% (95% CI, 44 to 66) for early signs of ischemia on noncontrast CT, and 73% (95% CI, 64 to 82) for HMPAO-SPECT.¹⁴

The natural history data suggest that HMPAO-SPECT has higher prognostic value the closer it is performed to stroke onset.²³ In a study of 458 consecutive patients using a receiver-operator analysis, HMPAO-SPECT was statistically better than the neurological deficit scores in predicting short-term outcome of ischemic stroke if performed within the first 72 hours after stroke onset compared with SPECT studies performed later during the first week.²³

In two studies, pretreatment HMPAO-SPECT also predicted intracranial bleeding in patients who received intra-arterial thrombolysis with rTPA or urokinase.^{21 22} The study by Ueda et al²² demonstrated that an ischemic region–to–cerebellar ratio <0.35 and an asymmetry index >1.5 were seen in all patients who developed hemorrhagic transformation. These semiquantitative criteria,²² as well as visual determination of the focal absence of brain perfusion,²³ might be evaluated further in a prospective study.

Another potential advantage of adding SPECT to the patient selection process is that rapid differentiation of the severity, extent, and location of cerebral ischemia could allow more homogeneous patient groups to be compared and could ultimately lead to a smaller sample size being required to demonstrate the benefit and safety of thrombolysis.

	Feasibility of Brain SPECT With HMPAO for Triage of Acute Stroke Patients

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
SPECT is one of several vascular imaging methods available that allow fast visualization of the depth, extent, and location of ischemia when the CT scan is negative or inconclusive.^{10 11 12} SPECT scanning with double- and triple-head cameras can be completed within 20 minutes, and even severely ill patients can be examined. Among various radiopharmaceutical agents currently in use, HMPAO is the most studied brain perfusion tracer.¹¹

Although SPECT is not regarded as an emergency procedure, it is feasible to have certified technologists on call who are able to arrive within 30 minutes. The technologist arrival and preparation of HMPAO would therefore take 1 to 1.5 hours. This is a long time, particularly when urgent thrombolysis is being considered. However, with 24-hour in-hospital coverage, HMPAO preparation would take 20 to 30 minutes, and a pretreatment HMPAO injection could be made within 30 to 40 minutes of emergency arrival of a patient with suspected acute ischemic stroke. Emergency nuclear medicine tests are already used for cardiac and lung disorders, which together with stroke and epilepsy could form the basis for routine 24-hour in-hospital coverage.

During business hours, HMPAO is either prepared and delivered by the central pharmacy within 1 hour, or if Technetium generators are available on site it can be prepared in approximately 20 minutes. At night, HMPAO preparation can be delayed for up to 1.5 hours. Either the stable or unstable HMPAO form may be used in the acute stroke setting. With stable HMPAO, the injection can be postponed up to 4 hours after preparation. The unstable form of HMPAO should be injected within 30 minutes of preparation. The preparation and injection of the tracer can be performed by a certified nuclear medicine technologist or other medical personnel (such as triage nurses or radiology technologists) if proper training and safety measures are provided. The normal adult dose of HMPAO for a 70-kg subject is 370 to 740 MBq (10 to 20 mCi) given intravenously in a bolus.

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.²⁴

	Imaging Properties of HMPAO Particular to Cerebral Ischemia

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
After intravenous injection, most of the HMPAO dose is distributed within 2 minutes in proportion to the regional cerebral blood flow.²⁴ The retention mechanism of HMPAO in brain tissue involves a chemical interaction with intracellular glutathione.²⁵ The tracer remains trapped, allowing reproducible imaging during the first 4 hours because of minimal washout from the brain. This feature is particular to HMPAO as opposed to other tracers and makes it suitable for a vascular imaging protocol piggybacked to a randomized clinical trial or a clinical study of rTPA during 0 to 3 hours to document pretreatment brain perfusion levels without delaying study medication.

The luxury perfusion syndrome during the subacute phase of stroke may produce increased uptake of the tracer,²⁶ and HMPAO distribution during the first hours of ischemia is proportional to actual cerebral blood flow when compared with ¹³³Xe regional cerebral blood flow measurements.^{27 28} For this reason, HMPAO is regarded as a perfusion- (as opposed to metabolism-) reflecting tracer, and its trapping mechanism makes it different from other tracers such as ¹²³I-iodoamphetamine and ^99mTc-ethyl cysteinate dimer.²⁵

Early presence of normal or increased HMPAO uptake is a prognostically favorable sign.^{17 23} The focal absence of HMPAO is a hallmark of arterial occlusion, with failure of collateral flow pointing to an increased risk of hemorrhagic transformation, brain edema, and death after stroke.^{13 14 15 16 17 18 19 20 21 22 23} These prognostically valuable measurements can be acquired within a relatively short imaging time with double- and triple-head cameras, typically taking 10 to 20 minutes to obtain an image resolution of 7 to 8 mm full width, half maximum. Since the goal is to identify patients at risk because of extensive lesions with deep ischemia when thrombolysis is considered, fast image acquisition is desirable, and even crude estimates of brain perfusion may prove clinically valuable.

	Visual and Semiquantitative Analysis of Brain SPECT Scans

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
The need for rapid perfusion imaging as an adjunct to the triage provided by clinical examination and CT scanning mandates fast and informative interpretation. Interpretation of CT scans is based on visual analysis and takes only a few minutes. The same principle is applicable to SPECT scans whereby one of five distinct brain perfusion patterns can be recognized visually.²³ Visual SPECT interpretations were reproducible between neurologists and nuclear medicine physicians in one study,²³ pending a prospective multicenter evaluation. 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 ). (2) The extent of the ischemic lesion is described by the number of regions 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.

These criteria (severity, extent, and location of ischemia) as well as asymmetry indexes described by Ueda et al²² may be relevant variables in ascertaining the risk of hemorrhage with thrombolysis and need to be studied prospectively. However, both visual and computer-assisted methods of interpretation need to be validated prospectively in clinical trials.

Although the same scale can be applied to the variety of semiquantitative methods so far proposed,^{15 16 17 18 19 20 21 22} it is not clear which numeric expression of the amount of HMPAO trapped in brain tissue would be best. It may be time consuming and impractical during triage to obtain ROI counts using sophisticated semiquantification, and the additional prognostic value of such quantitation over simple visual analysis has not been established. Two parameters should be calculated as suggested by Ueda et al,²² including the region-to-cerebellar ratio and asymmetry index. Another semiquantitative method called cortical rim segmentation allows semiquantification of asymmetry of HMPAO uptake between homologous ROIs together with volume and extent of the ischemic lesion.²⁹

Because both visual and semiquantitative analyses are aimed at identifying brain tissue at risk, both methods may prove useful, and corresponding threshold values for the severity of brain ischemia may be established prospectively. However, quantification of SPECT data requires rigorous pretrial quality control, since SPECT scanning is to some extent an operator-dependent procedure. Computerized algorithms that correlate best with outcome only can be established using a standardized approach set by a central image processing laboratory.

	Requirements for Quality Control and a Central Imaging Laboratory

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
Rigorous pretrial quality control and establishment of a central imaging laboratory are essential for a prospective multicenter study. The SPECT Safe Thrombolysis Study (SSTS) will prospectively determine the value of the SPECT parameters in predicting the risk of hemorrhagic complications of rTPA administered during the first 3 hours after stroke onset.³⁰ In this section, specific technical considerations and the duties of the central laboratory are presented.

Technical standards for brain imaging procedures have been published elsewhere.³¹ There are, however, several issues pertinent to the stroke setting that require cooperation between neurologists and nuclear medicine physicians. For instance, patients with acute stroke may not be able to tolerate scanning procedures for longer than 10 to 20 minutes. Therefore, by shortening scanning time, dual- or triple-head SPECT cameras are better suited for acutely ill patients than single-head cameras. Patient motion can be corrected by imaging software, and certain modifications in the scanning protocol may improve data acquisition. SPECT scanning should be accomplished at the distance closest to the patient's head and within the minimum time period required to achieve diagnostic resolution. The minimum scanning time can best be established in a prospective clinical trial of thrombolysis. Pretreatment brain perfusion scans can be acquired in 5-minute intervals and stored accordingly so that a comparison to clinical outcome events can determine the minimum time necessary for double- and triple-head cameras to acquire prognostically valuable images.

Pretrial quality control would need to be performed by the central imaging laboratory or the core lab. Before the entrance of a site into the trial, the core lab would evaluate the site's ability to produce high-quality images with a standard acquisition protocol. Each prospective site would provide digital copies of two studies of a standard phantom, one acquired with the protocol standard acquisition and one using a high count rate study. Since a standard object would be imaged, the first study would represent a standard quality image particular to the site, and the second study would show the maximum number of artifacts produced by the camera. This information would be useful for central interpretation of HMPAO scans. For this purpose, the hard copy of transaxial images would be submitted to the core lab together with the raw data recordings made on a digital medium. Once reconstructed at the core site and assessed for quality and resolution, the phantom images would serve as the baseline quality control assessment. During the trial, the principal duties of the core lab would be to receive all images from all sites, translate those SPECT images into a common standard format, reconstruct all images in a standard fashion using preselected filtering and reorientation methods, and apply standardized image analysis methods.

	Implementation of SPECT Through Clinical Trials in Acute Ischemic Stroke

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
Although HMPAO-SPECT is an FDA-approved test for diagnostic imaging of stroke patients, its clinical value has still not been clearly defined. Previously, this could be attributed in part to the absence of an effective treatment for stroke. Now, with implementation of intravenous thrombolysis, interest in SPECT imaging and its cost-effectiveness is still present.^{10 11} However, a prospective analysis must be performed to elucidate relevant variables associated with SHT associated with thrombolysis for ischemic stroke.^{31 32}

Such a prospective multicenter study should include rapid interpretation of the pretreatment levels of HMPAO to evaluate the clinical relevance of the variables of severity, extent, and location of ischemia as determined by SPECT. Both visual and semiquantitative methods of interpretation should be rigorously tested to see whether SPECT can identify tissue at risk for bleeding.

The goal of a prospective evaluation of SPECT would be to provide clinicians with an easy-to-use strategy to identify patients at risk for treatment complications. A trial will lead to clinical implementation of HMPAO-SPECT with rTPA, which could serve as a model for future clinical trials based on vascular imaging since different reperfusion strategies are emerging.

An attempt to evaluate and implement SPECT imaging in the acute stroke setting will require the close cooperation of neurologists and nuclear medicine physicians to achieve a better understanding of which patients should receive thrombolysis for ischemic stroke.

	Selected Abbreviations and Acronyms

 

CI = confidence interval HMPAO = hexamethylpropyleneamine oxime NIHSS = National Institutes of Health Stroke Scale NINDS = National Institute of Neurological Disorders and Stroke ROI = region of interest rTPA = recombinant tissue plasminogen activator SHT = symptomatic hemorrhagic transformation SPECT = single-photon emission computed tomography

	Acknowledgments

 
We wish to thank Lorraine Rufo, Len Ducker, and Thomas Overmyer, Amersham Healthcare, and Vicki Perry and Mike Dwyer, Cerebrovascular Advances Inc, for enthusiastic support and help in organizing the meeting. Several invited attendees were supported by CVA Inc and Genentech Inc. No other financial assistance for the meeting has been received or is pending from these sources. Dr Andrei Alexandrov is a fellow of the Heart and Stroke Foundation of Ontario, Canada. A grant-in-aid to Dr Alexandrov from Amersham Healthcare, Chicago, Ill, was provided to help defray the costs of this meeting and further protocol development.

	Appendix 1

Top Abstract Introduction Safety of Intravenous... Clinical and CT Findings... Experience With HMPAO-SPECT in... Feasibility of Brain SPECT... Imaging Properties of HMPAO... Visual and Semiquantitative... Requirements for Quality Control... Implementation of SPECT Through... Appendix 1 References

 
Participants of the Meeting, July 29-30, 1996, Marriott Hotel at the Medical Center, Houston, Tex, were Andrei V. Alexandrov, MD, University of Texas at Houston; Bruce Barron, MD, University of Texas at Houston; Sandra E. Black, MD, University of Toronto, Canada; Edward Bernbom, Amersham Healthcare; Nicholas Borys, MD, Amersham Healthcare, San Francisco, Calif; Patti Bratina, RN, University of Texas at Houston; Curtis B. Caldwell, PhD, University of Toronto, Canada; David Chiu, MD, University of Texas at Houston; Fong Wang Clow, PhD, Genentech, Inc; Michael D. Devous, Sr, PhD, University of Texas at Dallas; David Edwards, PhD, Cerebrovascular Advances, Inc; Juergen Froehlich, MD, Genentech, Inc; James C. Grotta, MD, University of Texas at Houston; Scott A. Kasner, MD, University of Texas at Houston; Derk Krieger, MD, University of Texas at Houston; Richard A. Kronmal, PhD, University of Washington, Seattle, Wash; Lamk A. Lamki, MD, University of Texas at Houston; Louise Lebrun, MD, Hôpital St Luc, Montreal, Quebec; Joseph C. Masdeu, MD, New York (NY) Medical College; David Sherman, MD, University of Texas–San Antonio; Michael A. Sloan, MD, University of Maryland at Baltimore; Jean Paul Soucy, MD, Hopital Notre Dame, Montreal, Quebec; Bjorn K. Sperling, MD, University of Copenhagen, Denmark; and Alan Waxman, MD, Cedars-Sinai Medical Center, Los Angeles, Calif.

Received February 24, 1997; revision received July 8, 1997; accepted July 15, 1997.

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30. Alexandrov AV, Black SE, Devous MD, Grotta JC, Masdeu JC, Sherman DG. SPECT Safe Thrombolysis Study (SSTS): patients, methods, and study design. Neurology. 1997;47:S33004. Abstract.

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