EAppendix
Standardization of TCD and MRA Performance
All sites participating in SONIA followed standardized guidelines for TCD and MRA performance as listed below.
TCD Performance Standards
1. Labs must follow Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL) standards and techniques. These include sonography performed through appropriate acoustic windows, arteries sampled at multiple depths, and acoustic intensity decreased when insonating over the eye.
2. Equipment type and probe specifications must meet ICAVL standards. These include transmit frequencies 2.0-2.5 MHz, range-gated Doppler with ability to adjust depth of range-gate, audio output, visual display of Doppler signal, and permanent record of waveforms [38].
3. Spectral analysis is required.
4. The signal must be optimized prior to measuring the velocity. The power should be on the lowest setting that gives a sharp waveform outline and a small sample volume should be used. The velocity scale should be set so the waveform fills ½ to ¾ of the scale. Once a signal is found, the vessel should be tracked and the probe manipulated to achieve the sharpest waveform outline and the highest velocity.
5. All normal arteries are examined in 5 mm increments and focal mean velocity elevation is identified.
6. Arteries are examined in 2 mm increments at the site of stenosis and highest mean velocity is measured.
7. A hard copy image of the highest mean velocity is submitted for each vessel insonated. A complete exam shows 13 vessels.
MRA Performance Standards
1. Technologist certified in MRI by ASRT or eligible candidate
2. Magnet field strength of at least 1.5 T
3. Multislab 3D Time-of-Flight (TOF) capability
4. Magnetization transfer suppression (MTS) to reduce background noise
5. Voxel size £1 mm3
6. TR £50 msec
7. TE £ 7 msec
8. Provide source and maximum intensity projection (MIP) images
9. Standardize number of MIP images on a page to 12 on 1 format (12 projections; 15° separation; 1.5 magnification); use 20 images on 1 film sheet format for source images
10. Edit MIP images tightly to eliminate extraneous noise while including all pertinent anatomy
Guidelines for angiography are the same as those used in WASID: contrast media must be 270-300 mg% and only single injection of a vessel is required.
Adherence to the TCD and MRA standards was ensured in two ways. Prior to entering the trial, each site recruited for SONIA must complete a SONIA Training Manual by submitting sample MRA and TCD case studies. These studies demonstrate that the site has the capability to meet the standards. Throughout the trial, every TCD or MRA is examined for quality, and sites are notified when studies are inadequate. Whenever possible, the quality problems are corrected before the study is centrally read. Only studies that meet the quality criteria are used in calculating PPV and NPV. Persistent failure to meet standards results in a site being dropped from SONIA.
Standardization of Readings
Standardized measurement methods are used to read all SONIA studies. Stenosis on angiograms is quantified using the general equation:
% stenosis = [1-(Dstenosis/Dnormal)] x 100
where Dstenosis is the diameter of the artery at its narrowest point. In the angiogram measurement methods previously published for extracranial arteries, Dnormal is measured as Ddistal [27, 28]. These methods were not appropriate for SONIA because the intracranial vessels are branched, narrow somewhat in distal parts, are often tortuous, and have no equivalent to the carotid bulb. SONIA angiograms are measured using criteria below.
Angiogram Measurement Criteria for Intracranial Vessels [29]
1. Ideally Dnormal is the diameter of the part of the artery proximal to the stenosis at its widest, non-tortuous segment.
2. If the entire proximal artery is diseased, Dnormal is the diameter of the part of the artery distal to the stenosis at its widest, non-tortuous segment.
3. If the entire artery is diseased, Dnormal is the diameter of the most distal, non-tortuous segment of the feeding artery with parallel margins.
4. For the intracranial carotid artery, Dnormal is the widest, non-tortuous portion of the petrous carotid artery if it is normal. If not, the most distal segment of the extracranial internal carotid artery is used.
5. For tandem lesions, the most severe lesion is measured.
6. If the lumen of the vessel cannot be seen, stenosis is defined as 99%.
SONIA readings are performed with a Mitutoyo 573-225-10 hand-held caliper.
There were no published measurement methods for intracranial vessels on MRA, but the one chosen for SONIA was selected because it is consistent and reproducible. Measurements are performed using the Mitutoyo 573-225-10 hand-held caliper following the same criteria used on angiograms. Flow gaps are identified visually. Over 50% stenosis or the presence of a flow gap defines a positive test. Whenever possible, both source and MIP images are examined, as source images have been shown to improve the sensitivity of MRA. When source and MIP images are available, MIP images are read if source images do not visualize a vessel. If both types of images visualize a vessel, the least severely diseased image type is measured as MRA generally overestimates degree of stenosis. Once image type, source or MIP, has been selected for a given vessel, the single view with the highest percent stenosis is measured.
Stenosis on TCD is identified using mean velocity cutpoints. The cutpoints are based on SONIA pilot data. Local readings are performed at each site automatically by the TCD equipment. Central readings are performed by manually drawing a horizontal midline on the hard copy of the waveforms. The horizontal midline separates three cardiac cycles of the waveform into equal parts, and mean velocity is read where the midline intersects the vertical axis. This method of measuring TCD was used in the STOP trial and found to be highly reproducible.