Assessment of brain perfusion with echo contrast specific imaging modes and Optison.
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Albumins↗
Biomedical subjects
Ulrich Bogdahn
Publications and source records attributed to Ulrich Bogdahn.
Cloning and characterization of the expression pattern of a novel splice product MIA (splice) of malignant melanoma-derived growth-inhibiting activity (MIA/CD-RAP) [corrected].
Melanoma-inhibiting activity/cartilage-derived retinoic acid-sensitive protein, a 11 kDa protein, is mainly expressed in cartilage during embryogenesis, and is related to invasion, metastasis, and immunomodulation of melanoma and glioma cells in vivo and in vitro. Here, we describe an alternative splice product of this gene termed melanoma-inhibiting activity (splice), lacking exon 2 of the original protein. A predicted frameshift by alternate splicing results in a unique C-terminal portion of the protein. Consistent with this, a protein migrating at the predicted molecular weight of the splice form (3.5 kDa) was detected using an N-terminal specific antibody. This band was undetectable when using a C-terminal specific antibody. In addition, we describe the expression pattern of melanoma-inhibiting activity (splice) in different human tumors. Expression was shown in tissue samples of five of six primary melanomas, 11 of 12 primary sites of metastatic melanomas, 10 of 10 systemic metastases of melanomas, four of four central nervous system metastases of melanomas, six of eight primary melanoma cultures, and five of five melanoma cell lines. Only a faint signal was obtained in tissue samples of five of six naevi. Interestingly, seven of eight nonmelanocytic tissue samples and five of seven glioma cell lines showed weak expression of melanoma-inhibiting activity (splice). Approaching first functional aspects, reverse transcriptase-polymerase chain reaction showed weak expression of melanoma-inhibiting activity (splice) in relation to melanoma-inhibiting activity in nonmelanocytic and strong expression in melanocytic cells. Staining with a specific anti-serum raised against a synthetic peptide resembling the amino acid sequence of melanoma-inhibiting activity (splice) showed a more nuclear staining pattern in comparison with melanoma-inhibiting activity. Furthermore, incubation of melanoma and glioma cell cultures with transforming growth factor-beta2 showed inverse regulation of the mRNA of melanoma-inhibiting activity and melanoma-inhibiting activity (splice), both suggesting also a different function within the physiologic role of this unique family of proteins. Melanoma-inhibiting activity (splice) has no homology to any other known protein so far. Whereas the biologic function of melanoma-inhibiting activity (splice) is not clear yet, it might provide a relevant diagnostic and therapeutic tool for malignant melanomas.
Alternative Splicing↗
SonoVue (BR1), a new long-acting echocontrast agent, improves transcranial colour-coded duplex ultrasonic imaging.
BACKGROUND AND PURPOSE: Visualization of normal or pathological flow in the intracranial arteries using transcranial colour-coded duplex sonography (TCCS) is occasionally obstructed by insufficient temporal bone windows, unfavourable insonation angles, or low flow velocities or volumes. SonoVue (BR1) is a new, long-acting echocontrast agent, which could be helpful in these instances. METHODS: SonoVue was studied in two separate multicentre investigations of patients with insufficient bone windows (BR1-014 with 73 patients and BR1-017 with 40 patients) using an identical protocol. The agent was given intravenously as a bolus in four different doses (0.3, 0.6, 1.2 and 2.4 ml). Evaluation was performed on-site and off-site with video clips. RESULTS: The contrast agent was well tolerated. As compared to the precontrast scans, SonoVue facilitated the visualization of vessel patency, stenosis, occlusion, and collateral flow, decreased the need for additional tests, and had an impact on the patient's treatment. In 66-74%, a non-diagnostic investigation was converted into a diagnostic investigation. The highest dose (2.4 ml) allowed for a clinically useful signal enhancement of a median 1.9-6.3 min. CONCLUSIONS: SonoVue at a single dose of 1.2 or 2.4 ml is effective in increasing the detection of normal or pathological flow in the intracerebral arteries in patients who do not have a fully diagnostic unenhanced TCCS examination.
Aged↗
Observation on the integrity of the blood-brain barrier after microbubble destruction by diagnostic transcranial color-coded sonography.
OBJECTIVE: To investigate alteration of the blood-brain barrier from ultrasonic contrast agent destruction by diagnostic transcranial color-coded sonography using gadolinium-enhanced magnetic resonance imaging. METHODS: Healthy male volunteers received 10 mL (400 mg/dL) of Levovist (SH U 508A; Schering AG, Berlin, Germany; n = 6) or 3 mL of Optison (FS069; Mallinckrodt Inc, St Louis, MO; n = 4) followed by 0.3 mmol/kg magnetic resonance imaging contrast agent (Magnevist; Schering) intravenously. Then transcranial color-coded sonography was performed with a conventional color duplex sonographic system, which insonated the brain in a slightly angulated axial plane with temporal average intensity of less than 700 mW/cm2 or acoustic pressure amplitude of less than 2.69 MPa, attenuated by the temporal bone. Before, immediately after, and 2 hours after insonation, T1-weighted axial magnetic resonance imaging was performed. All magnetic resonance images were individually assessed, and T1 signal intensities were measured in 2 regions of interest in both hemispheres at the 3 time points. RESULTS: No focal contrast enhancement or damage to the brain and no significant difference between T1 signal intensities in the right and left brain regions could be detected during early or late phases when either ultrasonic contrast agent was used. CONCLUSIONS: This bioeffects study gives further evidence of the safety of ultrasonic destruction of Levovist and Optison microbubbles by diagnostic transcranial color-coded sonography. However, more subtle local effects may have been missed by gadolinium-enhanced magnetic resonance imaging. Studies on diagnostic contrast-enhanced transcranial color-coded sonography as well as microbubble-based drug delivery strategies should consider ultrasonic contrast agent microbubble characteristics and concentration as well as ultrasound transmission power levels.
Adult↗
Contrast-Enhanced Transcranial and Extracranial Duplex Sonography: Preliminary Results of a Multicenter Phase II/III Study with SonoVuetrade mark.
Transcranial sonography is an ultrasonographic application with real problems of insufficient signal to noise ratio, which make it a primary candidate for applying ultrasonographic contrast enhancing agents. Within an international randomized multicenter phase II/III study, we investigated ten patients with insufficient Doppler signal retrieval using transcranial and extracranial color-coded duplex sonography to define safety, toxicity, optimal dosing, and the potential of the new ultrasound contrast agent SonoVue(trade mark). Patients were studied with standard color duplex systems. SonoVue(trade mark) was administered by IV bolus injection at four different doses. Efficacy parameters included the assessment of global quality of Doppler investigations, color Doppler (CD), and spectral Doppler (SD) evaluated by semiquantitative analysis using a four-point scale from 0 to 3 (very poor to excellent) and the duration of clinically useful signal enhancement. In addition, CD enhancement, evaluated at best signal enhancement, was assessed using a five-point scale, from no enhancement, slight, moderate, optimal to excessive (0-4). All examinations were compared to "gold" standard imaging (magnetic resonance imaging, digital subtraction angiography) to evaluate diagnostic confidence at optimum dosage. No serious adverse events were observed. Mean signal increase over baseline in CD or SD was 2 out of 4 points. Mean time to appearance of contrast enhancement was 22.8 seconds (9-52 sec) at the optimal dosage. The mean duration of enhancement was 281 seconds(20-593 sec) at the optimal dosage, which was of 2.4 ml of SonoVuetrade mark in nine patients. CD and SD signal enhancement (n = 20, CD + SD) was considered optimal in 12 of 20, excessive in 1 of 20, and moderate or insufficient in 5 of 20 and 2 of 20 cases, respectively. There was a tendency for superior improvement in CD signal enhancement. Diagnostic confidence was improved in 8 of 10 cases without false diagnostic conclusions. SonoVuetrade mark has been demonstrated to be a powerful and safe echo signal enhancing agent, which significantly improves transcranial and extracranial ultrasound investigations and increases the confidence in diagnosis.
Journal Article↗
Transcranial color-coded duplex sonography of the carotid siphon: the coronal approach.
Transcranial color-coded sonography can assist in the assessment of the carotid siphon segments C1 and C5 employing two standardized coronal image planes. In 32 volunteers mean velocities in the C1 and C5 were 41+/-16 and 30+/-10 (cm/s+/-S.D.), pulsatility indices (PI) 0.92+/-0.22 and 0.93+/-0.27, and resistance indices (RI) 0.58+/-0.08 and 0.55+/-0.12, respectively. Concluding, this technique is useful in assessing the carotid siphon with the most robust parameters being PI and RI requiring further validation by the "gold standard" angiography.
Adolescent↗
Melanoma-inhibiting activity (MIA/CD-RAP) is expressed in a variety of malignant tumors of mainly neuroectodermal origin.
BACKGROUND: The identification of tumor-specific antigens is an important topic for potential therapeutic and diagnostic applications. Melanoma-inhibiting activity (MIA/CD-RAP), a protein involved in the regulation of tumor growth, invasion, dissemination and immunoreactivity in melanomas and other tumors, is expressed by almost all melanomas and melanoma metastases screened to date so far. Elevated levels of melanoma-inhibiting activity (MIA/CD-RAP) have also been measured in a subgroup of patients with advanced stage breast carcinomas. MATERIALS AND METHODS: To further evaluate the extent and distribution of MIA/CD-RAP expression, early passage melanoma, glioma and other tumor cell lines as well as non-malignant cell lines were screened for the expression of MIA/CD-RAP by PCR, Western blot and immunohistochemistry. RESULTS: All melanomas tested (n = 19) expressed high levels of MIA mRNA and protein. A high incidence of MIA expression was also found in glial tumors (6 out of 27). In contrast, MIA message (mRNA) could not be detected in non-glial CNS-tumors (n = 13). In addition, in CSF of patients harboring a brain tumor, significant higher levels of MIA protein were detectable compared to the systemic values. MIA/CD-RAP-message was detectable in 7 out of 20 systemic tumors, mainly carcinomas of the colon (2 out of 2) and, in low levels, in 8 out of 20 normal non-transformed cell cultures, for example fibroblasts and peripheral lymphocytes. These data indicate that MIA/CD-RAP is widely expressed in human and murine primary cell cultures and cell lines, with nevertheless relative high specificity for melanocytic tumors. Measurements of MIA protein in the cerebrospinal fluid (CSF) and serum of patients harboring metastatic melanoma revealed higher levels in the CSF than in serum. To address functional aspects of MIA/CD-RAP expression, we stably transformed a MIA/CD-RAP-negative glial tumor cell line to express MIA/CD-RAP. When tested in colony forming assay (CFA), these clones showed a marked reduction in colony formation. CONCLUSION: According to these results, MIA/CD-RAP seems to exert a general function for invasive and metastatic tumors.
Central Nervous System Neoplasms↗
Preoperative evaluation of carotid artery stenosis: comparison of contrast-enhanced MR angiography and duplex sonography with digital subtraction angiography.
BACKGROUND AND PURPOSE: Contrast-enhanced MR angiography and extracranial color-coded duplex sonography are noninvasive, preoperative imaging modalities for evaluation of carotid artery stenosis. Innovative techniques and improvements in image quality require frequent reassessment of accuracy, reliability, and diagnostic value compared with those of digital subtraction angiography (DSA). We evaluated contrast-enhanced MR angiography and duplex sonography compared with DSA for detection of high-grade carotid artery stenoses. METHODS: Four readers, blinded to clinical symptoms and the outcome of other studies, independently evaluated stenoses on contrast-enhanced MR angiograms in 71 vessels of 39 symptomatic patients. Duplex sonography was also performed in all vessels. The severity of stenosis was defined according to North American Symptomatic Carotid Endarterectomy Trial criteria (0-29%, 30-69%, 70-99%, 100%). Results of both modalities were compared with the corresponding DSA findings. RESULTS: Contrast-enhanced MR angiography had a sensitivity and specificity of 94.9% and 79.1%, respectively, for the identification of carotid artery stenoses of 70% or greater. Sensitivity and specificity of duplex sonography were 92.9% and 81.9%, respectively. Combining data from both tests revealed a sensitivity and specificity of 100% and 81.4%, respectively, for concordant results (80% of vessels). CONCLUSION: Concordant results of contrast-enhanced MR angiography and duplex sonography increase the diagnostic sensitivity to 100%. The reliability of MR angiography is comparable to that of DSA. The combination of contrast-enhanced MR angiography and duplex sonography might be preferable over DSA for preoperative evaluation in most patients, thus reducing the risk of perioperative morbidity and improving the overall outcome.
Adult↗