Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA): Design of a Prospective, Multicenter Trial of Diagnostic Tests

Background and Relevance: Intracranial atherosclerosis is responsible for 70,000 ischemic strokes each year in the USA. Noninvasive testingsuch as transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) to identify intracranial atherosclerosis is in widespread use, but has not been rigorously validated against the gold standard, catheter angiography. The recently NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial will compare warfarin with aspirin for stroke prevention in patients with intracranial atherosclerosis. WASID requires performance of angiography along with TCD and MRA, providing an opportunity to critically evaluate these noninvasive tests. Main Objective: The purpose of the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) study is to develop the noninvasive diagnosis of intracranial atherosclerosis. The primary aim of SONIA is to define velocity values on TCD and anatomic abnormalities on MRA that identify severe (50–99%) intracranial stenosis of large, proximal arteries seen on catheter angiography. SONIA will define the criteria, or ‘cutpoints’, for an abnormal TCD or MRA and show that they perform with a reliable positive predictive value (PPV). Study Design: SONIA will be conducted in collaboration with WASID. Study-wide cutpoints defining positive TCD and MRA have been developed and reviewed by the site investigators of WASID. Hard copy angiography, TCD and MRA generated in WASID will be centrally read in SONIA. TCD and MRA cutpoints seek to achieve a target PPV of 80% for the identification of severe intracranial stenosis on angiography. Conclusions: Central readings will be used to validate the cutpoints and to develop measures of negative predictive value, and inter- and intra-observer variability. Sensitivity and specificity will be determined after adjustment for verification bias and employed in receiver-operator characteristic analyses. SONIA will use these techniques to develop TCD and MRA cutpoints that minimize the clinical consequences of test errors occurring in the noninvasive evaluation of patients with suspected intracranial atherosclerosis.

[1]  A. Luft,et al.  Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part II--Clinical aspects and recommendations. , 2000, Neurosurgery.

[2]  A R Luft,et al.  Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part I--Pathophysiological and pharmacological features. , 2000, Neurosurgery.

[3]  H. A. Smith,et al.  A standardized method for measuring intracranial arterial stenosis. , 2000, AJNR. American journal of neuroradiology.

[4]  A. Alexandrov,et al.  Accuracy and Criteria for Localizing Arterial Occlusion With Transcranial Doppler , 2000, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[5]  D B Matchar,et al.  Incidence and occurrence of total (first-ever and recurrent) stroke. , 1999, Stroke.

[6]  A. Alexandrov,et al.  Yield of transcranial Doppler in acute cerebral ischemia. , 1999, Stroke.

[7]  M. Takahashi,et al.  Intracranial vascular stenosis and occlusion: MR angiographic findings. , 1997, AJNR. American journal of neuroradiology.

[8]  G. Schuierer,et al.  Intracranial vascular stenosis and occlusion: comparison of 3D time-of-flight and 3D phase-contrast MR angiography , 1998, Neuroradiology.

[9]  M A Waclawiw,et al.  Stroke prevention trial in sickle cell anemia. , 1998, Controlled clinical trials.

[10]  A. Missoum,et al.  Detection of vertebrobasilar intracranial stenoses: transcranial Doppler sonography versus angiography , 1997, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[11]  A. Donald.  Verification bias: a pitfall in evaluating screening tests. , 1996, Nursing research.

[12]  E. Feldmann,et al.  Performance of carotid ultrasound in evaluating candidates for carotid endarterectomy is optimized by an approach based on clinical outcome rather than accuracy. , 1996, Stroke.

[13]  E. Oddone,et al.  Endarterectomy for asymptomatic carotid artery stenosis. , 1995, JAMA.

[14]  J S Lewin,et al.  High Resolution, Magnetization Transfer Saturation, Variable Flip Angle, Time‐of‐Flight MRA in the Detection of Intracranial Vascular Stenoses , 1995, Journal of computer assisted tomography.

[15]  M. B. Brown,et al.  The Warfarin-Aspirin Symptomatic Intracranial Disease Study , 1995, Neurology.

[16]  W. Steinbrich,et al.  Intracranial arteries: prospective blinded comparative study of MR angiography and DSA in 50 patients. , 1995, Radiology.

[17]  R. Adams,et al.  Transcranial Doppler Correlation With Angiography in Detection of Intracranial Stenosis , 1994, Stroke.

[18]  M. Takahashi,et al.  Intracranial vascular stenosis and occlusion: diagnostic accuracy of three-dimensional, Fourier transform, time-of-flight MR angiography. , 1994, Radiology.

[19]  P. Gorelick.  Distribution of atherosclerotic cerebrovascular lesions. Effects of age, race, and sex. , 1993, Stroke.

[20]  G. Albers,et al.  Stroke prevention in nonvalvular atrial fibrillation: A review of prospective randomized trials , 1991, Annals of neurology.

[21]  C. Warlow,et al.  MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis , 1991, The Lancet.

[22]  J. Ley-Pozo,et al.  Noninvasive detection of occlusive disease of the carotid siphon and middle cerebral artery , 1990, Annals of neurology.

[23]  E. Feldmann,et al.  Chinese‐white differences in the distribution of occlusive cerebrovascular disease , 1990, Neurology.

[24]  A. Fox,et al.  Clinical events following neuroangiography: a prospective study. , 1987, Stroke.

[25]  R. Whaley,et al.  Complications following transfemoral cerebral angiography for cerebral ischemia. Report of 159 angiograms and correlation with surgical risk. , 1987, Surgical neurology.

[26]  J. Fleiss.  The design and analysis of clinical experiments , 1987 .

[27]  J. Bogousslavsky,et al.  Atherosclerotic disease of the middle cerebral artery. , 1986, Stroke.

[28]  K. Davis,et al.  The prognosis of carotid siphon stenosis. , 1986, Stroke.

[29]  L. Solberg,et al.  Cerebral atherosclerosis in New Orleans. Comparisons of lesions by age, sex, and race. , 1985, Laboratory investigation; a journal of technical methods and pathology.

[30]  M. Modic,et al.  Intracranial internal carotid artery stenosis: longterm prognosis. , 1982, Stroke.

[31]  P. Holland,et al.  Discrete Multivariate Analysis. , 1976 .

[32]  E. Keeler,et al.  Primer on certain elements of medical decision making. , 1975, The New England journal of medicine.

[33]  W. S. Fields,et al.  Joint Study of Extracranial Arterial Occlusion II. Arteriography, Techniques, Sites, and Complications , 1968 .

[34]  W. S. Fields,et al.  Joint Study of Extracranial Arterial Occlusion as a Cause of Stroke: I. Organization of Study and Survey of Patient Population , 1968 .

[35]  Prognosis of patients with symptomatic vertebral or basilar artery stenosis. The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study Group. , 1998, Stroke.

[36]  R. Sacco,et al.  Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. , 1995, Stroke.

[37]  R. Edelman,et al.  Intracranial vertebrobasilar system: MR angiography. , 1994, Radiology.