shu-508 and Brain-Neoplasms

Transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCD) are ultrasound neuroimaging modalities that can provide useful diagnostic information on the intracranial vasculature with a high degree of safety. However, the skull can serve as an effective bone barrier, reducing reflected ultrasound signal by up to 100% in some patients and thereby challenging both technical quality and clinical interpretation of TCD and TCCD. Levovist is an IV ultrasound echo-enhancement agent that withstands passage through the heart and lung, increasing signal throughout the entire vascular pool. As part of European phase II and III clinical trials, this agent has been studied for utility of enhancement for TCD and TCCD studies in patients with signs and symptoms of cerebrovascular disease. All patients had either highly insufficient or nonexistent native signal on baseline transcranial ultrasound studies before administration of Levovist. The agent was administered at concentrations of 200, 300, or 400 mg/ml, and studies were repeated. In all studies, 300 to 400 mg/ml was sufficient for enhancement, although in several phase II studies 300 mg/ml Levovist was the preferred dosage in terms of superior imaging with a low level of side effects. In a phase III study, Levovist improved diagnostic utility of TCD and TCCD without compromising safety. Reviews of clinical phase II and III studies show that echo enhancement with Levovist facilitates routine clinical investigation of intracranial vascular anatomy in patients with signs and symptoms of intracranial vascular disease. In patients with no native signal, Levovist-enhanced imaging permits visualization of small peripheral vessels, venous circulation, tissue characteristics, and perfusion data, with no significant loss of safety.

Topics: Aged; Animals; Brain Neoplasms; Cerebrovascular Disorders; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Contrast Media; Female; Humans; Male; Middle Aged; Polysaccharides; Ultrasonography, Doppler, Color; Ultrasonography, Doppler, Transcranial

To study the potential of contrast material-enhanced transcranial color-coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization.. Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography.. All lesions were hyperechoic on B-mode US scans except one grade 2 astrocytoma. The location and extent of hyperechoic lesions correlated well with findings on CT scans and MR images. After injection of contrast material, color Doppler flow signals were seen in nine of 14 low-grade lesions and 14 of 14 high-grade lesions. High-grade malignant tumors always had atypical arterial and venous Doppler spectra with irregular distribution of Doppler shift and signal intensities; these atypical flow patterns were also detected in some low-grade tumors.. In addition to depiction of primary CNS tumors in B-mode, contrast-enhanced TCCS enables evaluation of vascularization associated with tumor parenchyma.

Topics: Adult; Aged; Angiography, Digital Subtraction; Brain Neoplasms; Cerebral Angiography; Cerebral Arteries; Contrast Media; Female; Humans; Male; Middle Aged; Polysaccharides; Tomography, X-Ray Computed; Ultrasonography

Malignancies affecting the central nervous system are intractable to conventional therapies thereby requiring an alternative strategy, such as ultrasound irradiation.. We originally designed a transducer for intracranial insonation and investigated the effect of 210.4 kHz ultrasound on malignant glioma cells.. The insonation of 2.61 W/cm2 effectively disrupted the malignant cells. This effect was reinforced by the echo-contrast agent, Levovist. The condition was applied to tumor-bearing animals and external insonation inhibited subcutaneous tumor growth. It also repressed the growth of intracranially implanted tumors and prolonged survival of the animals. When Levovist was stereotactically injected into the tumors, the effect of insonation was significantly enhanced.. A neuronavigation system or stereotactic device has been used commonly for patients with brain tumor. Administration of combination therapy consisting of insonation and a local echo-contrast agent will have a role in improving the treatment for malignant gliomas.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Cell Membrane; Contrast Media; Female; Glioma; Humans; Microbubbles; Polysaccharides; Rats; Rats, Inbred F344; Sonication; Ultrasonic Therapy; Ultrasonography; Xenograft Model Antitumor Assays

The goal of this study was to evaluate intraoperative power Doppler ultrasonography when used with a contrast-enhancing agent for operations on intracranial tumors.. Forty intracranial tumors were examined using power Doppler ultrasonography with a galactose microparticle-based ultrasonographic contrast-enhancing agent during operations on the brain. The tumors included 37 intracranial neoplasms (14 gliomas, six meningiomas, three hemangioblastomas, two malignant lymphomas, three other primary neoplasms, nine metastatic tumors, and three nonneoplastic lesions). All patients also underwent computerized tomography and magnetic resonance imaging, and all but three of the patients underwent digital subtraction (DS) angiography. Before injection of the ultrasonographic contrast agent, intra- and peritumoral power Doppler flow signals were detected in 32 of the intracranial tumors. After the injection, the signals were enhanced in blood vessels around the tumors and in the tumor parenchyma in 36 tumors. The duration of contrast enhancement continued for 70 to 365 seconds (mean 251.8 +/- 69 seconds) after the injection. Among the tumors, hemangioblastomas displayed particularly strong contrast enhancement. In these intracranial tumors, the echo signals obtained using contrast-enhanced power Doppler ultrasonography correlated with DS angiographic staining. Power Doppler ultrasonograms with the appropriate contrast agent provided better data on the precise real-time position of the tumors and their relationship to adjacent vessels than ultrasonograms obtained before the injection of the contrast agent.. Intraoperative power Doppler ultrasonography performed using a contrast-enhancing agent can facilitate intraoperative real-time navigation and assessment of the intratumoral vasculature and peritumoral vessels, particularly for tumors having abundant vessels such as hemangioblastomas.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Angiography, Digital Subtraction; Brain; Brain Neoplasms; Cerebral Angiography; Child; Child, Preschool; Contrast Media; Female; Glioma; Humans; Image Enhancement; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neovascularization, Pathologic; Neuronavigation; Polysaccharides; Sensitivity and Specificity; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial

Echo-enhancing agents improve the signal intensity of transcranial Doppler signals, enabling a novel approach of three-dimensional transcranial vascular imaging by Doppler ultrasound. The basic principle, system requirements and early clinical results with a custom built system are described. Transcranial color Doppler imaging was performed through the temporal bone acoustic window. During i.v. administration of the transpulmonary stable, galactose-based echo-enhancer Levovist (Schering) the video output of the ultrasound scanner was digitized and the spatial position of the recorded frames was simultaneously registered using a mechanical position sensor. After automatic segmentation of the color information, the 3D datasets were reconstructed offline using a Unix-based workstation (Silicon Graphics). Visualization was achieved by maximum intensity projection or surface visualization techniques. Administration of Levovist resulted in good enhancement of the vascular Doppler signal intensity, enabling acquisition of a 3D dataset of the complete circle of Willis with an imaging window of approximately 3-5 min for one i.v. injection. The vascularity of tumors could be recorded as a 3D dataset and further analyzed. The power Doppler technique with echoenhancement proved a valuable tool for 3D dataset recording. 3D datasets clearly facilitated the diagnosis of the vascular anatomy and lesion vascularity and provided additional information on localization of feeders, vascular displacement and extent of tumor vascularity.

Topics: Blood Flow Velocity; Brain Diseases; Brain Neoplasms; Computer Systems; Contrast Media; Diagnosis, Differential; Humans; Image Enhancement; Image Processing, Computer-Assisted; Neovascularization, Pathologic; Polysaccharides; Sensitivity and Specificity; Ultrasonography, Doppler, Transcranial

Topics: Adolescent; Blood Flow Velocity; Brain Neoplasms; Cerebrovascular Circulation; Child; Contrast Media; Humans; Intracranial Arteriovenous Malformations; Polysaccharides; Ultrasonography, Doppler, Color; Ultrasonography, Doppler, Transcranial; Ultrasonography, Interventional