| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Pediatric Imaging |
1 From the Departments of Radiology (A.J.M., J.E.H.T., M.C.D., G.S.D.) and Pediatrics (R.V.I., M.G.S.), University of Mississippi Medical Center, Jackson. From the 1999 RSNA scientific assembly. Received March 29, 2000; revision requested May 10; revision received July 14; accepted August 2. Address correspondence to A.J.M., 226 Oakwood Ct, Winston-Salem, NC 27103 (e-mail: abemalouf@yahoo.com).
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
MATERIALS AND METHODS: One hundred twenty-five asymptomatic patients aged 2–16 years with sickle cell anemia or sickle cell-ß thalassemia were examined by using transcranial duplex power Doppler US with a 2.5-MHz transducer and classified according to STOP criteria. The results were compared with those obtained in the nonduplex STOP study. Eight of 10 patients with abnormal results, as well as one who had normal results and a subsequent stroke, were examined with MR imaging and MR angiography.
RESULTS: Ten (8.0%) patients were judged to have abnormal findings by using the duplex Doppler US and STOP criteria compared with 9.4% of patients in the nonduplex US STOP study. Of the eight patients with abnormal transcranial Doppler US results who underwent MR imaging and MR angiography, six had abnormal MR imaging findings and all eight had abnormal MR angiographic findings.
CONCLUSION: The STOP protocol can be reproduced by using duplex power Doppler US. Abnormal results with the STOP criteria strongly suggest vascular abnormality.
Index terms: Brain, infarction, 13.4352, 13.78 • Cerebral blood vessels, US, 178.12984, 178.12989 • Sickle cell disease (SS, SC), 13.651, 13.652 • Ultrasound (US), power Doppler studies, 178.12984, 178.12989
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
In a Medical College of Georgia study with 315 patients examined by using nonduplex TCD US, Adams et al (4) found that the patients with time-averaged maximum velocities (TAMVs) of 200 cm/sec or higher in the distal ICA, ACA-MCA bifurcation, or MCA had a markedly increased risk of stroke. Identification of this high-risk group allowed evaluation of chronic transfusion as a means of preventing initial stroke in the larger follow-up Stroke Prevention Trial in Sickle Cell Anemia (STOP) study, which involved 1,934 patients and had results that demonstrated a 92% decrease in the relative stroke rate in the treated group (1).
The results of this trial resulted in a clinical alert by the National Heart, Lung, and Blood Institute, which recommended TCD US screening in children with sickle cell disease. The authors were requested by pediatric hematologists to begin screening patients by using the STOP protocol, which we did by using power Doppler US. In this article we report our experience in implementing the nonduplex US STOP protocol, with duplex power Doppler US used to identify patients at high risk for stroke.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The clinicians ordered magnetic resonance (MR) imaging and MR angiography for patients with abnormal TCD US results, when feasible, to correlate for evidence of vascular abnormality or ischemia, because these patients were candidates for chronic transfusion. MR imaging and MR angiography were ordered for eight of 10 patients with abnormal TCD studies. Because the US and MR studies were performed as a requested standard of clinical service care, pursuant to the National Heart, Lung, and Blood Institute clinical alert, and the data were later collected through a review of records with patient anonymity protected, exemption of investigational review board approval was granted.
An Elegra unit (Siemens, Issaquah, Wash) and 2.5-MHz pulsed Doppler probe were used for all US studies. TCD US was performed by using power Doppler imaging with the STOP technique, which was adapted for duplex imaging (1,4). All studies were performed by sonographers who had attended workshops on the STOP technique, and they were supervised and the results interpreted by one of three radiologists (A.J.M., J.E.H.T., M.C.D.).
An acoustic window through the thin temporal bone was found for examination of the MCA, ACA, distal ICA and bifurcation, and posterior cerebral artery. The circle of Willis was identified at the level of the cerebral peduncles with power Doppler imaging. The most peripheral portion of the MCA was identified and velocity measurements were obtained with Doppler gate advancement in 2–3-mm increments. At the bifurcation, flow is bidirectional, with flow within the MCA toward and flow within the ACA away from the transducer. Measurements were made in both the ACA and the MCA portions of the bifurcation.
The gate was then advanced medially into the ACA, and measurements were taken. The bifurcation was again found, and the probe was angled slightly caudad to obtain measurements in the distal ICA, usually 4 mm proximal to the bifurcation. The probe was then angled posteriorly to evaluate the proximal posterior cerebral artery, with flow toward the transducer. The basilar artery was examined with the patient in the decubitus position, the neck flexed, and the probe angled through the foramen magnum in the midline. The vertebral arteries may be seen joining as they form the basilar artery at the medullopontine junction. From this position, flow in the basilar artery is away from the transducer.
We used color Doppler US for our studies initially but quickly switched to power Doppler US, because we found that it enabled us to visualize vessels much better. We used the same approach and vessels as those used in the STOP study, similar Doppler sample volumes (5 mm), and no angle correction (ie, 0°), because the nonduplex machines did not have angle correction capability. In all segments, particular attention was paid to recording the highest velocity obtained. If a patient underwent more than one examination during the study period, the highest value was used for classification, because the velocity measurement may be underestimated but should not be overestimated with no angle correction and declining velocities can represent stenoses exceeding critical levels (4,6).
We chose to manually measure the TAMV, as in the STOP study, to eliminate any changes that might be introduced by electronic wave-follower forms of measurement. As in the STOP study, the TAMV was measured by placing the cursor at a level such that a horizontal line through that level would make the area above the line and below the peak velocity envelope in systole equal to the area below the line and above the peak velocity envelope in diastole (Fig 1). Although our machine had no full-width horizontal cursor to facilitate measurement across several regular cardiac cycles, as in the STOP study, we found that in the majority of cases in which the TAMV was not near a cutoff point, we could place the short horizontal cursor and visually extend the line to accurately estimate the TAMV (Figs 2, 3). If the velocity was close to the abnormal cutoff point of 200 cm/sec, we zoomed the image to one on one on the workstation, filmed the zoomed image, and used a sharp film pencil to draw the horizontal line across all the cycles on the image to better visualize the correct level. These methods allowed us to avoid a possible problem associated with using electronic wave-follower measurement.
|
|
|
|
|
|
|
The patients were classified as in the STOP study, as summarized in Table 1. Because the patients with abnormal results were candidates for chronic transfusion, which is not without risk, and there is some day-to-day variation in velocities, when the study results were abnormal, the patient returned in a week to confirm the abnormal value (1,4,11). Although two abnormal studies were required to confirm an abnormal case and thus make the patient a candidate for transfusion, these studies did not have to be consecutive. Patients who were classified as "conditional" (ie, with velocities 
170 cm/sec but not meeting abnormal criteria) were scheduled for follow-up at less than the 6-month screening interval—usually 2 months. If readable signals in both the right and left MCA and bifurcation could not be obtained, the study was classified as inadequate, and the patient was reexamined as soon as possible—the following week, if feasible. At least two sonographers attempted to obtain readable signals at any reattempted previously inadequate examination.
|
MR angiography involved transverse three-dimensional time-of-flight imaging with a spoiled gradient-echo sequence (49.0/6.9, 25° flip angle, 512 x 224 matrix), first-order flow compensation, and superior and inferior saturation pulses. Sixty 1-mm-thick partitions were acquired. Maximum intensity projection was used to create collapsed transverse images and coronal projection images. To avoid the possible problems related to maximum intensity projection imaging, individual partitions were reviewed in each case (7). All MR studies were reviewed by a single neuroradiologist (G.S.D.) without knowledge of the Doppler US findings. Clinical follow-up was supervised by two pediatric hematologists (R.V.I., M.G.S.).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
|
All eight patients with abnormal TCD US and MR angiographic findings were started on transfusion therapy. Two of the patients with abnormal velocities were started on transfusion therapy on the basis of TCD US findings alone and did not undergo MR studies. One patient with high normal velocities had a stroke 3
months after his imaging studies. MR imaging depicted chronic right periventricular ishcemic changes and an acute right midfrontal gyrus infarct in the anterior cerebral arterial distribution. MR angiography depicted mild stenoses of the left proximal MCA and right proximal ACA.
At follow-up, one (0.8%) patient with a high normal velocity (167 cm/sec) had a stroke 3 months after his initial study; results of the repeat study performed at the time of the stroke revealed a velocity of 171 cm/sec. At the time this article was written, no patients with conditional velocities had had a stroke. One patient with abnormal velocities had a stroke between the time of TCD US and the initiation of transfusion therapy. At the time of this writing, the status of two patients with conditional velocities had progressed such that they had abnormal velocities at follow-up. One patient with two inadequate studies had a stroke 12 months after his last TCD US study. At the time of this writing, our follow-up ranged from 12 to 24 months, and no other strokes had occurred.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
TCD US findings associated with cerebrovascular disease in patients with sickle cell anemia have been described by several authors (3,6–9,15). Seibert et al (16) reported nine TCD US findings associated with cerebrovascular disease in sickle cell disease. To our knowledge, Adams et al (3,6,10,17) were among the first investigators to use nonduplex Doppler US to examine patients with sickle cell disease and thereby define the expected blood flow velocity values in children without known cerebrovascular disease, report elevated velocities in patients with angiographically proved lesions, and demonstrate the effectiveness of nonduplex Doppler US in screening for cerebrovascular disease. Expanding on an earlier study, Adams et al (4) reported on a Medical College of Georgia prospective study of nonduplex Doppler US performed in 315 children who had sickle cell anemia or sickle cell-ß thalassemia without a history of stroke at entry. With a 40–60-month follow-up, patients with blood flow velocities lower than 170 cm/sec in all vessels had a 2% risk of subsequent stroke and were later designated the "normal" group. Those patients with velocities of 170 cm/sec or higher in any vessel but lower than 200 cm/sec in the distal ICA or MCA had a 7% risk of subsequent stroke and were designated the "conditional" group. Those with velocities of 200 cm/sec or higher in the distal ICA or MCA were noted to have a 40% incidence of stroke at follow-up and designated the "abnormal" group. Identification of the latter, high-risk group made possible the evaluation of periodic blood transfusions for prevention of initial strokes; this treatment had been shown to greatly reduce the incidence of recurrent strokes (18,19). The results of STOP demonstrated a 92% difference in the rate of initial stroke between patients with abnormal velocities who received transfusions and those with abnormal velocities who did not (1). This finding led to early termination of the trial and the issuance of a clinical alert by the National Heart, Lung, and Blood Institute, in which TCD screening in children aged 2–16 years with sickle cell disease and without a history of stroke was recommended (20).
We expect the TAMV measurement method described herein to be new to many radiologists (21,22). We used this method because it was used in the STOP study, which produced the velocities used to classify the patients, and it has not yet been shown that these values are valid with wave-follower forms of measurement. In addition, as mentioned earlier, early in our experience, while using both forms of measurement, we noted problems with the wave-follower capturing signals clearly above the velocity envelope; this was possibly related to the relatively high gain settings used for these studies.
Although a full-width horizontal cursor, as is available on nonduplex STOP machines, would be ideal, our method of visually extending the level of the short cursor works well when the TAMV is not near a cutoff point for abnormal values. When the TAMV is near a cutoff point, the method used in the STOP study—that of a full-width horizontal cursor across several regular cardiac cycles—can be reproduced by filming the image and drawing a horizontal line (Fig 1) with a sharp film pencil. Although the 200 cm/sec mark is always present on our scale, for the conditional cutoff point of 170 cm/sec or other values that are not precisely marked on the scale that may be used in the future, the small cursor can be set at the desired value, the image filmed, and the relationship of the drawn line to the cursor ascertained. Although we did not have nonduplex machines for direct comparison, side-by-side comparisons of velocity values obtained in the same patient with both nonduplex and duplex machines by using both manual and wave-follower measurement methods would be ideal to evaluate any differences. Future inclusion of a full-width horizontal cursor on the duplex machines used by most radiologists would be extremely helpful.
MR imaging findings in sickle cell disease, both in symptomatic and asymptomatic patients, have been reported (7–9,13,16,23–26). Some investigators have reported that lesions at MR imaging in asymptomatic patients are associated with a high incidence of subsequent stroke (24). Although six (75%) of eight patients with abnormal TCD US findings in our study had abnormalities at MR imaging, in the original STOP study, only 44 (35%) of 127 patients who had abnormal TCD findings had abnormal MR imaging findings (1).
Results of previous reports (7,25) have shown good correlation between MR angiography and angiography in symptomatic patients with sickle cell disease. Seibert et al (16) reported a strong correlation between a combination of both positive TCD findings and positive MR angiographic findings, and subsequent stroke, whereas a negative MR angiogram was associated with a low risk of subsequent stroke. Data obtained by Abboud et al (27) from follow-up of children in the STOP trial who underwent MR studies suggest that TCD US is more sensitive than MR angiography in enabling the identification of children with sickle cell disease who are at risk for stroke. Although they noted that the patients with normal MR angiograms or mild abnormalities at MR angiography were more likely to have resolved abnormal TCD findings at follow-up than were the patients with moderate to severe stenoses or occlusions, three of nine patients with abnormal TCD US scans and subsequent stroke had initially normal MR angiograms. Therefore, more data on the follow-up of larger numbers of patients who undergo MR angiography seem to be necessary to determine whether MR angiography can be helpful in further quantifying the risk of stroke in these patients. The fact that all of the MR angiographic studies performed in our study patients with abnormal TCD US scans were abnormal supports the theory that these patients are at high risk for subsequent stroke. The clinical stroke that occurred in one patient between the time of TCD US, MR imaging, and MR angiography and the beginning of transfusion, as well as the subclinical acute infarct noted on the MR image in another patient, further confirms the high-risk nature of this group.
As noted earlier, one of the patients with all velocities lower than 170 cm/sec had a subsequent stroke. The causes for this false-negative case might be technical error in the TCD US study, artery-to-artery embolism from abnormal intima (4,24) without hemodynamically significant stenosis, or small-vessel disease, which are believed to be causes of stroke in such patients (24–26). Although we are currently scheduling follow-up studies at 2-month intervals for the patients with conditional velocities, this protocol would be expensive over time, and patient compliance with these short-term follow-up appointments has been a problem. Results of further follow-up of these patients may demonstrate a longer interval at which these patients—particularly those with velocities in the lower conditional range—can be safely followed up. Alternatively, if further study results indicate that MR angiographic findings strongly correlate with subsequent risk of stroke, selective use of MR angiography in patients with conditional velocities might obviate further short-term follow-up.
One of the eight patients with inadequate studies subsequently had a clinical stroke. Although poor penetration of the skull by the ultrasound beam may be a cause of inadequate studies, this is relatively unusual in children (6), and in our study, we were able to visualize the brain parenchyma with varying amounts of vascular flow at power Doppler imaging in six (75%) of eight patients in whom an adequate study ultimately could not be obtained, including the patient with the subsequent stroke. The inability to find vascular signals for one or more vessels with nonduplex equipment or the lack of depiction of a vessel with visualization of the brain parenchyma or other vessels with duplex equipment has been reported in symptomatic patients with vascular occlusion (3,15) and in asymptomatic patients who later developed symptoms (4). One of the patients classified as a normal case in the Medical College of Georgia study had no vascular signals of the ICA or MCA on one side and later had a clinical stroke (4). (Inadequate classification was not used in the MCG study.) Therefore, we believe that a patient with an inadequate study, especially when there is visualization of the brain parenchyma or other vessels, should be considered for other studies, such as MR imaging or MR angiography.
Power Doppler US has been reported to be superior to conventional color Doppler US in the depiction of intracranial vessels and able to depict vessels relatively independent of the angle of the vessel to the US beam (28,29). This was also our experience. From the examiner’s point of view, we found that the excellent depiction of the circle of Willis afforded by power Doppler US allowed quick orientation to the vessels and rapid, confident placement of the sample volume. Therefore, the learning curve was relatively short. In addition, in some patients, the locus of increased velocity was quite short, and it was possible to pass over it without realizing it. The images from previous studies, with the excellent vascular visualization enabled by using power Doppler US in documenting a site of previous concern, allows these areas of concern to be confidently identified for careful repeat examination and optimal measurement.
Our experience indicates that by adhering carefully to the techniques of the STOP protocol, the results can be duplicated by using duplex power Doppler US, with the added benefits of excellent vascular visualization. We believe that in addition to paying meticulous attention to technique, it is important to maintain a database of the patients examined, which includes a record of velocities, classifications, MR findings, and clinical follow-up, both to monitor results and for possible use as other criteria are found to be useful.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
Abbreviations: ACA = anterior cerebral artery, ICA = internal carotid artery, MCA = middle cerebral artery, STOP = Stroke Prevention Trial in Sickle Cell Anemia, TAMV = time-averaged maximum velocity, TCD = transcranial Doppler
Author contributions: Guarantor of integrity of entire study, A.J.M.; study concepts and design, all authors; literature research, A.J.M.; clinical studies, A.J.M., J.E.H.T., M.C.D., R.V.I., M.G.S.; data acquisition, A.J.M.; data analysis/interpretation, A.J.M., J.E.H.T., M.C.D.; manuscript preparation, A.J.M., J.E.H.T., M.C.D.; manuscript definition of intellectual content, all authors; manuscript editing, A.J.M.; manuscript revision/review, all authors; manuscript final version approval, all authors.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  J. Krejza, W. Rudzinski, M.A. Pawlak, M. Tomaszewski, R. Ichord, J. Kwiatkowski, D. Gor, and E.R. Melhem Angle-Corrected Imaging Transcranial Doppler Sonography versus Imaging and Nonimaging Transcranial Doppler Sonography in Children with Sickle Cell Disease AJNR Am. J. Neuroradiol., September 1, 2007; 28(8): 1613 - 1618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Oguz, X. Golay, F. B. Pizzini, C. A. Freer, N. Winrow, R. Ichord, J. F. Casella, P. C. M. van Zijl, and E. R. Melhem Sickle Cell Disease: Continuous Arterial Spin-labeling Perfusion MR Imaging in Children Radiology, May 1, 2003; 227(2): 567 - 574. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |
