Echocontrast-Enhanced Transcranial Color-Coded Sonography for the Diagnosis of Transverse Sinus Venous Thrombosis
Background and Purpose Early diagnosis of cerebral transverse sinus venous thrombosis (TSVT) is difficult because of nonspecific and variable clinical presentations. Therefore, we evaluated the diagnostic value of transcranial color-coded duplex sonography (TCCS) after administration of an echocontrast-enhancing agent (cTCCS) in clinically suspected TSVT.
Methods We examined 14 patients (6 men, 8 women; mean age, 48 years; range, 18 to 70 years) with signs and symptoms suggestive of cerebral TSVT. Color-coded signals from the contralateral transverse sinus were displayed transtemporally before and after injections of an echocontrast agent by TCCS. Sonographic findings were correlated with MRI and MR venography (MRV).
Results Before echocontrast enhancement, TCCS displayed color Doppler signals in 7 of 28 transverse sinus. Echocontrast TCCS obtained sufficient color signals in 27 of 28 transverse sinus. Thus, diagnostic confidence was achieved in all but 1 patient. In 13 patients, cTCCS identified 3 cases with symmetrical blood flow in the transverse sinus, which was confirmed by MRV. Accordingly, asymmetry of venous blood flow was correctly assessed by cTCCS in the other 10 patients. In 6 of these 10 patients, cTCCS demonstrated residual color flow signals, which on MRI/MRV corresponded to partial TSVT (4 cases) and to hypoplasia (1 case) of the transverse sinus. One case of complete thrombotic occlusion of the transverse sinus was missed by cTCCS because of color Doppler signals originating from an adjacent dural fistula. Echocontrast TCCS diagnosis of occlusion of a transverse sinus was confirmed by MRI/MRV in all cases (aplasia of transverse sinus, n=1; complete TSVT, n=3). Systolic peak flow velocities were significantly decreased in hypoplastic or partially occluded transverse sinus (9.4±4.0 cm/s) and significantly increased contralaterally (28.4±6.5 cm/s) with respect to patients with symmetrical appearance of the transverse sinus (17.5±1.9 cm/s) (P<.05).
Conclusions TCCS examination of the cerebral venous system is difficult without contrast media application and almost useless for the study of TSVT. However, cTCCS is of practical value in the initial workup of patients with clinically suspected TSVT and may provide further insight for follow-up studies in view of monitoring the recanalization.
Diagnosis of TSVT is difficult because of the nonspecific clinical presentation in many cases and the occurrence in association with numerous conditions and diseases.1 2 3 4 5 Furthermore, the infrequent performance of early cerebral angiography may prevent or delay accurate diagnosis of TSVT, particularly in cases with subacute onset of symptoms. More recently, MRI combined with MRV has been introduced as a reliable noninvasive examination technique that is able to demonstrate both venous blood flow abnormalities and intraluminal clot signals.6 7 8 However, limited availability, significant costs, and technical difficulties in performing MRV in severely ill patients are current limitations of this noninvasive examination technique.
For more than a decade, transcranial Doppler sonography has been an established method for the routine evaluation of the arterial cerebral circulation. However, its use for the assessment of the intracranial veins was limited9 10 11 12 because of the considerable anatomic and hemodynamic variabilities of the venous system. TCCS, introduced more recently, permits the real-time visualization of the intracranial vascular anatomy and blood flow dynamics and has also been applied for studies of the cerebral venous system in normal subjects and selected patients with superior sagittal sinus thrombosis.13 In patients with TSVT, however, this technique has thus far not been used. Since these patients are particularly difficult to diagnose otherwise and may remain misdiagnosed, we investigated the diagnostic significance of TCCS with additional enhancement of color Doppler signals (cTCCS) by means of an echocontrast agent in patients with clinically suspected TSVT.14
Subjects and Methods
During a 7-month period, 14 consecutive patients (6 men [mean age, 51 years; range, 26 to 70 years]; 8 women [mean age, 46 years; range, 18 to 65 years]) with a presumed diagnosis of TSVT were studied. Eight patients were examined in the acute setting (<1 week); in 6 patients, time between onset of symptoms to diagnostic workup in our institution was delayed (patient characteristics and the initial clinical presentation are summarized in the Table⇓).
We used an Acuson 128 XP sonographic system with a 2-MHz phased-array sector transducer for the ultrasound examinations. The technical principles of color Doppler flow imaging have been reported elsewhere.15 16 The contralateral transverse sinus was visualized transtemporally with the transducer parallel to the orbitomeatal line. Scanning depths were regularly set between 140 and 160 mm to sufficiently visualize the contralateral skull. The internal occipital protuberance was used as a landmark for the torcular herophili. Evaluation of the intensity of color Doppler signals as an indicator of venous blood flow was performed before and after one to three injections of Levovist. With respect to venous blood flow, color Doppler signals were classified after application of the echocontrast agent as follows: 0, absent (no signal obtainable); 1, weak (thin and discontinuous cTCCS signal); 2, normal (continuous cTCCS signal); and 3, excessive (broadened cTCCS signal with substantial FLASH artifacts). Whereas sufficient Doppler signals before echocontrast application were only rarely obtained, postechocontrast peak flow velocities of the transverse sinus were regularly recorded by means of the integrated pulsed-wave Doppler system. The same protocol was used to evaluate the contralateral transverse sinus through the opposite transtemporal bone window.
Levovist consists of transpulmonary stable microbubbles formed in a galactose suspension. This causes a signal increase of approximately 25 dB and therefore an improved signal-to-noise ratio. Depending on the signal increase, the following concentrations were used17 : 16 mL of 200 mg/mL, 10 mL of 300 mg/mL, and 8 mL of 400 mg/mL. Bolus injections were made into a cubital vein at a constant injection speed (1 to 2 mL/s). Echocontrast-enhanced TCCS examinations (cTCCS) were performed after informed consent was given. A total of 34 echocontrast injections (mean, 2.4 injections per patient; range, 2 to 4 injections) were needed with concentrations of 200 mg/mL (n=20), 300 mg/mL (n=12), and 400 mg/mL (n=2) to achieve adequate enhancement of venous color Doppler signals. However, with increasing experience, fewer injections and lower concentrations were required to establish the diagnosis.
Investigations were performed within 1 week after the sonographic study by an investigator blinded to the cTCCS results. MR images were obtained using a 1.5-T superconductive MRI system (Magnetom SP63, Siemens Erlangen) with a circular polarized head coil. Each patient underwent a routine protocol including T1-, proton-density-, T2-, and postcontrast T1-weighted (0.01 mmol/kg Gd-DTPA) imaging. Additionally, the patients underwent flow-sensitive, FLASH, 2D MRV (repetition time, 32 milliseconds; echo time, 10 milliseconds; flip, 60°; field of view, 230 mm; matrix, 2562; acquisitions, 1; measurement time, 8 minutes) postprocessed by the maximum intensity projection algorithm and axial T1 images after administration of gadolinium. Finally, in some patients, a new technique of 3D digital subtraction MRV using precontrast and postcontrast strongly T1-weighted MPRAGE imaging with high tissue resolution was applied. The final MRV data were obtained from MPRAGE subtraction images. MRV was evaluated with respect to flow asymmetries of the transverse sinus; axial MRI was evaluated for the presence of a clot signal.18
Before echocontrast enhancement, TCCS displayed venous color Doppler signals in only 7 of 28 transverse sinus. Color signals in these 7 cases were inadequate for the assessment of normal or pathological venous blood flow (Figure⇓). Application of the echocontrast agent sufficiently improved the ultrasound signal in 27 of 28 transverse sinus (Table⇑). Thus, satisfactory diagnostic confidence was achieved in all but 1 patient (patient 2) in whom visualization of one transverse remained insufficient.
In the remaining 13 patients, cTCCS identified 3 cases with symmetrical blood flow in the transverse sinus, which was confirmed by MRV (patients 10, 12, and 13). Accordingly, asymmetry of venous blood flow was correctly assessed by cTCCS in the other 10 patients. Six of these 10 patients (patients 1, 6, 7, 8, 11, and 14) with side-to-side differences of transverse sinus blood flow cTCCS demonstrated residual color flow signals, which on MRI and MRV corresponded to partial TSVT by an intraluminal clot signal in 4 cases and to hypoplasia of the transverse sinus in 1 case. However, thrombotic occlusion of the transverse sinus was missed by cTCCS in 1 patient because of misinterpretation of color Doppler signals originating from an adjacent dural fistula (patient 7).
Echocontrast TCCS diagnosis of complete absence of blood flow in a transverse sinus was confirmed by MRI/MRV in all cases (patients 3, 4, 5, and 9) (aplasia of transverse sinus, n=1; complete TSVT, n=3). Additionally, MRI and MRV revealed 1 case (patient 5) of an incomplete thrombosis of the superior sagittal sinus.
Complete thrombotic occlusion was almost exclusively seen in patients examined immediately after onset of symptoms (patients 5, 7, and 9), whereas delayed diagnostic workup, mainly because of a prolonged and nonspecific presentation, might have resulted in partial recanalization in others.
Systolic peak flow velocities within the proximal transverse sinus in patients with symmetrical appearance of the venous blood flow showed minor side-to-side differences. Velocities ranged from 15 to 20 cm/s (17.5±1.9 cm/s). In comparison, flow velocities were significantly decreased in hypoplastic or partially occluded transverse sinus (9.4±4.0 cm/s) and significantly increased contralateral to a transverse sinus with decreased or absent venous blood flow (28.4±6.5 cm/s) (P<.05).
Levovist injections were well tolerated, and no side effects were noted during or after the echocontrast injections.
The present study confirms the common experience of most investigators working with conventional transcranial Doppler and TCCS, which is that reliable sonographic assessment of the cerebral venous system without ultrasound enhancement is extremely difficult. Only 7 of 28 transverse sinus were visualized on TCCS before the application of an echocontrast enhancing agent, while cTCCS provided adequate diagnostic information about blood flow in the transverse sinus in 13 of 14 patients. However, while normal cTCCS findings securely ruled out thrombosis of the transverse sinus, differentiation of TSVT from congenital hypoplasia or aplasia of the transverse sinus was difficult because direct sonographic visualization of the clot was impossible. Unfortunately, congenital asymmetries of the transverse sinus are not uncommon: Hacker19 reported a prevalence of aplasia of 14% for the left and 3.3% for the right transverse sinus. Intra-arterial angiography and MRV present similar problems of differentiating between thrombotic occlusion and normal variants of the paired transverse sinuses, in particular if dilated or tortuous collateral veins as a sign of venous obstruction are absent.20 Therefore, in all cases with absent or significantly reduced blood flow in the transverse sinus, confirmation of TSVT by visualization of the clot signal on MRI is required regardless of the vascular examination technique, which initially detected absent or significantly asymmetrical blood flow.
Although a reliable sonographic differentiation between asymmetrical and thrombosed transverse sinus was not feasible in the present study, significantly increased color-coded blood flow in the contralateral transverse sinus often combined with elevated venous blood flow velocities, indicating that compensatory venous drainage was found to be more pronounced in cases with thrombotic occlusion compared with congenital asymmetries. Increasing knowledge of the sonographic appearance of the cerebral venous system using cTCCS will certainly improve the assessment of the variations of the collateral blood flow pathways and pathological hemodynamics in TSVT. In the present study, adequate adjustment of the insonation angle for recording pulsed-wave Doppler velocity spectra was technically difficult because of the tilted course of the transverse sinus. With regard to this methodological limitation, peak systolic velocities for normal transverse sinus of the present study were slightly higher than those published thus far (17.5 versus 12.0 cm/s).13 Transverse sinus judged to be hypoplastic or partially thrombosed showed significantly decreased venous blood flow velocities with respect to the contralateral transverse sinus, as well as when compared with that in normal control subjects.
Early diagnosis of cerebral TSVT may be difficult because of its variable and frequently nonspecific clinical appearance. In this respect, CT is still important in the initial diagnostic workup of clinically suspected TSVT for the exclusion of other diseases, such as ischemic brain infarct, intracerebral hemorrhage, tumor, and abscess.21 However, in transverse TSVT, CT findings are not specific and may even be normal. Since cTCCS is a noninvasive and easily applicable examination technique, it is an ideal complementary screening procedure, in particular in patients with soft signs of TSVT, especially where MRI studies including MRV are not available.
Recanalization of the thrombosed venous sinus represents the most important prognostic factor.22 MRI has shown its capacity to document thrombus regression. In comparison, because of the invasiveness and the potential risks, angiography is not suited for repeated examinations to monitor the time course of recanalization.4 23 The findings of the present case series suggest that follow-up examinations using cTCCS may provide an adequate alternative for monitoring the degree of recanalization of TSVT, although the reproducibility of the cTCCS results has yet to be evaluated.
In conclusion, our findings demonstrate the potential diagnostic significance of echocontrast-enhanced TCCS in the initial diagnostic workup of patients with clinically suspected TSVT. In addition, cTCCS is a promising method for follow-up studies in patients with transverse TSVT, thus providing relevant information to guide further diagnostic and therapeutic measures.
Selected Abbreviations and Acronyms
|cTCCS||=||transcranial color-coded duplex sonography with echocontrast-enhancing agent|
|FLASH||=||fast low-angle shot|
|TCCS||=||transcranial color-coded duplex sonography|
|TSVT||=||transverse sinus venous thrombosis|
We thank M. Garcia and Dr S. Meairs for their editorial comments. We are indebted to Dr A. Bauer from the Schering AG for his helpful support concerning the echocontrast agent.
- Received September 26, 1996.
- Revision received January 23, 1997.
- Accepted January 27, 1997.
- Copyright © 1997 by American Heart Association
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