Thrombolytic therapy, the only proven acute treatment for ischemic stroke, aims to recanalize arterial occlusion. There is experimental evidence of enhancement of thrombolysis through ultrasound at various frequencies both continuous and interminttent pulse wave. Ongoing clinical trials are examining thrombolysis with tissue plasminogen activator in combination with catheter-based intraarterial or transcranial ultrasound. CLOTBUST is an on going phase II clinical trial of transcranial pulse wave ultrasound at 2 MHz and thrombolysis.

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Ultrasound has been in use for diagnostic imaging and therapy in medicine for half a century. Recently, there have been numerous reports on the application of thermal and nonthermal ultrasound energy for treating various diseases of the brain. In addition to thermal ablation of brain tumors, non-thermal ultrasound combined with drugs has shown considerable promise, especially for treatment of vascular diseases of the brain and regenerative medicine. Ultrasound energy can enhance the effects of thrombolytic agents such as urokinase for treatment of stroke. Therapeutic ultrasound catheters are currently being developed. Non-invasive methods such as high-intensity focused ultrasound (HIFU) in conjunction with MRI and CT are already being applied in the clinical field. Chemical activation of drugs by ultrasound energy for treatment of tumors is another new field recently termed “sonodynamic therapy”. Combination of genes with microbubbles has given rise to great hopes that it can be applied to gene therapy for the brain. Various examples of ultrasound combined modalities are under investigation, and could lead to revolutionary methods of brain therapy.

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PURPOSE: This study was conducted to assess the usefulness of ultrasonography combined with angiography for carotid stent placement.
MATERIALS AND METHODS: Six patients who underwent carotid stent placement between June and December 2002 were examined by ultrasonography using a SONOLINE Elegla machine (Siemens) with a 5.1-9.0-MHz linear probe. Smart Stent (Cordis) was used for all patients. Ultrasonographic examination including longitudinal and transverse views of the common and internal carotid arteries was done before and after pre-balloon dilatation, after stenting, and before and after post-balloon dilatation. The change in the form of plaque was evaluated at the time of both pre-balloon dilatation and post-balloon dilatation. We decided the positioning of the stent under ultrasonographic guidance, but placed the stent under fluoroscopic guidance.
RESULTS: It was easier to position the balloon and stent relative to the plaque using ultrasonography than using angiography. The change in plaque form resulting from extension and contraction of the balloon was directly observed. It was possible to decide the position of the stent based on the grade of atherosclerotic change in the carotid artery and also to evaluate the adjustment of the stent in the carotid artery.
CONCLUSION: Combined use of angiography and ultrasonography for stent placement is practicable and convenient.

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We evaluated the tendency for MES to appear during cerebral angiography (AG). The subjects were 89 patients (M/F=44/45, mean age=53 y). During AG, a transcranial Doppler (TCD) study was performed in two channels (proximal and distal MCA) by TC2020. The protocol for MES detection was a threshold level of 6 to 9 dB, and a saving time of 1 s. Micro-bubble was defined at more than 400 Hz, and solid embolus was less than 400 Hz for frequency analysis of MES. Within 10 days after AG, MRI was performed in 17/89cases (19%).
Results: TCD studies were not possible in 11 women and 3 men, and there were 75 detectable cases. MES were detected in 62 of 75 cases. The numbers of MES in each AG were 5±4.4 on regular AG, 2±2.2 on test injection, and 2±0.7 during catheterization.
Frequency analysis for MES showed that solid embolus was mostly observed during catheterization in 13% (8/62), and that micro-bubbles were detected during injection of contrast medium in 87% (54/62). Among the 17 MES-positive cases, two had ischemic lesions detected on MRI.
It is concluded that use of a minimum necessary amount of contrast medium and careful handling of catheters are recommended in order to decrease the incidence of MES.

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The purpose of the present study was to determine the clinical significance of deep venous thrombus (DVT) in legs diagnosed by ultrasonography in patients with paradoxical brain embolism. The authors performed ultrasonography on the legs of 67 consecutive patients who were diagnosed as having paradoxical brain embolism. We compared the clinical background between DVT-positive and DVT-negative groups, and between hemiplegic-side DVT and non hemiplegic-side DVT groups. DVT were detected in 27 (40%) of all patients. Patients were significantly older in the DVT-positive group (p = 0.044). National Institutes of Health Stroke Scale (NIHSS) scores on admission were worse in the DVT-positive group (p = 0.066). Time from the onset of brain embolism to performance of ultrasonography was longer in the DVT-positive group (p = 0.068). DVTs were detected in hemiplegic-side legs in 14 of 19 patients with hemiparesis. NIHSS score on admission was significantly worse in the hemiplegic-side DVT group (p = 0.018). Period between the onset of brain embolism and performance of ultrasonography was longer in the hemiplegic-side DVT group (p = 0.174). In conclusion, DVTs detected by ultrasonography may be de novo thrombi acquired after the onset of brain embolism.

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We evaluated the incidence of deep vein thrombosis (DVT) in patients with hemiplegia after stroke using ultrasonography.
Thirty patients with post-stroke hemiplegia (Brunnstrom stage 1-2) were enrolled. We evaluated clinical signs of DVT, ultrasonographic findings and D-dimer an average of 19.1 days after onset. Ultrasonographic findings were classified into three groups: (1) DVT: visualization of an intraluminal thrombus, lack of venous compressibility, and lack of signal on the color flow image. (2) Moyamoya-echo: intraluminal high echo signal with venous compressibility. (3) Normal findings.
Nine patients (30%) had direct findings of DVT in the affected lower extremity. Six had proximal and three had calf DVT. Two of nine had DVT in the non-affected lower extremity. Moyamoya-echo was seen in six patients (20%). Patients with DVT and moyamoya-echo were older than patients with normal findings. D-dimer assays of patients with DVT showed higher values compared with moyamoya-echo and normal findings. Patients with hemiplegia after stroke were candidates at high risk of DVT. Ultrasonography was useful for screening of DVT. We think that Moyamoya-echo is a precursor sign of DVT.

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A proposal has been made to introduce a new Japanese guideline for detection of micro-embolic signals using trans-cranial Doppler (TCD). This guideline is in accordance with the Consensus on Micro-Embolus Detection by TCD proposed by the International Consensus Group on Micro-Embolus Detection in 1998. Micro-embolic signals are called HITS or MES. HITS include artifacts in place of MES. Recommended settings are: (1) use of a 2-MHz probe; (2) sample volume within 10 mm; (3) power set as low as reasonably possible; and (4) use of a headband to affix the TCD probe. The characteristics of HITS/MES are: (5) an intensity at least 3 dB higher than the background that reflects the blood stream; (6) a recording time of more than 30 minutes but not more than one hour to maintain the normal brain temperature; and (7) signals without associated sounds or a low emboli-blood ratio (EBR) excluding HITS. Other recommendations include: (8) recording HITS as digital data, using digital audio tape or CD-R; (9) having data double-checked by an expert who is not familiar with the clinical profile of the examinee; and (10) checking all data manually. The results are better than those obtained from an automatically detected HITS/MES system that is not yet at the completion stage.

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