Biomedical subjects

Kohkan Shamsi

Publications and source records attributed to Kohkan Shamsi.

10 recordsLinked to original sources

PubMed2006

Vasovist-enhanced MR angiography.

Vasovist (MS-325) is the first intravascular contrast agent approved for use with magnetic resonance angiography in the European Union. Vasovist reversibly binds to albumin, providing extended intravascular enhancement compared to existing extracellular magnetic resonance contrast agents. Prior to approval, Vasovist underwent extensive testing to evaluate the safety and efficacy of the drug; the clinical trials program included blinded, placebo-controlled dose ranging, efficacy in a variety of vascular beds (AIOD, renal, pedal), examination of potential drug interaction with warfarin and comparison with XRA. The clinical trials show that Vasovist-enhanced MR angiography is safe and well-tolerated in patients with vascular disease, effective for the detection of vascular stenosis and aneurysms, significantly more accurate (both more sensitive and specific) than non-contrast MR angiography for the diagnosis of vascular stenoses, and similar to conventional angiography for the overall characterization of vascular disease, without the need for catheterization.

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PubMed2006

A summary of safety of gadofosveset (MS-325) at 0.03 mmol/kg body weight dose: Phase II and Phase III clinical trials data.

OBJECTIVE: We sought to summarize the Phase II and Phase III clinical trials safety data for gadofosveset (Vasovist, MS-325), a new magnetic resonance angiography contrast agent. MATERIALS AND METHODS: Subjects with known or suspected vascular disease were administered 0.03 mmol/kg gadofosveset (767 subjects) or placebo (49 subjects) in phase II and phase III studies. Overall safety data were pooled from 8 studies and included adverse event monitoring, clinical laboratory assays, vital signs, oxygen saturation, physical examination, and electrocardiography. The safety was monitored for 72 to 96 hours postinjection (PI), and safety comparison with x-ray angiography using iodinated contrast media also was performed in 318 subjects. In the phase II trial, 5 doses of gadofosveset and placebo were evaluated. In this study, 38 patients were administered placebo and 39 patients received 0.03 mmol/kg gadofosveset. RESULTS: In pooled data, treatment related adverse events were reported by 176 (22.9%) patients receiving gadofosveset and by 16 (32.7%) patients receiving placebo. In phase II trial, treatment-related adverse events were reported by 13 of the 39 (33.3%) patients receiving gadofosveset and 9 of the 38 (23.7%) patients receiving placebo. No severe or serious adverse events were reported in either gadofosveset or placebo groups in this phase II trial. Pooled data revealed no clinically significant trends in adverse events, laboratory assays, vital signs, or oxygen saturation. A QTc prolongation of 2.8 milliseconds was observed at 45 minutes after MS-325 injection; however, this trend was similar to that of the placebo group at the same time point (3.2 milliseconds). CONCLUSION: Gadofosveset has exhibited a good safety profile and can be safely administered as an intravenous bolus injection. The overall rate and experience of adverse events was similar to that of placebo. The safety profile of gadofosveset is comparable with that of other gadolinium contrast agents as reported in the literature.

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PubMed2005

Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study.

PURPOSE: To assess prospectively the efficacy and safety of postcontrast magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) compared with that of precontrast MR imaging in patients who are known to have or are suspected of having liver lesions and who are scheduled for hepatic surgery. MATERIALS AND METHODS: Investigational review board approval and written informed consent were obtained. HIPAA went into effect after data collection. A total of 172 patients were enrolled. After precontrast MR imaging, 169 patients (94 men, 75 women; mean age, 61 years; age range, 19-84 years) received an intravenous bolus of 25 micromol/kg Gd-EOB-DTPA and underwent dynamic gradient-recalled-echo and delayed MR imaging 20 minutes after injection. Arterial and portal phase computed tomography (CT) were performed within 6 weeks of MR imaging. The standard of reference was surgery with intraoperative ultrasonography (US) and biopsy and/or pathologic evaluation of resected liver segments and/or 3-month follow-up of nonresected segments if intraoperative US was not available. Three blinded reviewers and unblinded site investigators identified liver lesions on segment maps. The Wilcoxon signed rank test was used to compare differences in per-patient sensitivity of precontrast and postcontrast MR images. Adverse events were recorded, and patient monitoring and laboratory assay were performed at time of injection and up to 24 hours after contrast material administration. RESULTS: At MR imaging, 316 lesions were identified in 131 patients. In 77% (P = .012), 72% (P = .15), and 71% (P = .027) of patients for readers 1, 2, and 3, respectively, more lesions were seen at precontrast and postcontrast MR imaging combined than at precontrast MR imaging alone. Sensitivity values for blinded readings were significantly greater at postcontrast MR imaging than at precontrast MR imaging for two of three blinded readers. For all blinded readers, combined precontrast and postcontrast MR images showed no difference in sensitivity compared with helical CT scans. The use of MR imaging, however, yielded fewer patients with at least one false-positive lesion (37%, 31%, and 34% of patients for readers 1, 2, and 3, respectively) than did helical CT (45%, 36%, and 43% of patients for readers 1, 2, and 3, respectively). CONCLUSION: Compared with precontrast MR imaging, postcontrast MR imaging with Gd-EOB-DTPA demonstrated improved sensitivity for lesion detection in the majority of blinded readers, with no substantial adverse events.

Adult↗

PubMed2005

MR angiography of aortoiliac occlusive disease: a phase III study of the safety and effectiveness of the blood-pool contrast agent MS-325.

PURPOSE: To evaluate prospectively the safety and effectiveness of aortoiliac magnetic resonance (MR) angiography enhanced with MS-325 (gadofosveset trisodium) at a dose of 0.03 mmol/kg; effectiveness was defined as accuracy relative to the reference standard, conventional angiography. MATERIALS AND METHODS: Study was approved by institutional review boards of participating institutions, and required national approvals were obtained. Study protocol conformed to Good Clinical Practice guidelines, and informed patient consent was obtained. Patients with known or suspected peripheral vascular disease received 0.03 mmol/kg MS-325 for aortoiliac MR angiography. They were also examined with conventional angiography. MS-325-enhanced MR was evaluated for safety and effectiveness. Along with unenhanced two-dimensional time-of-flight MR angiography, it was compared with conventional angiography for presence of vascular stenosis. Student t tests were used to identify significant improvement in diagnostic sensitivity, specificity, and accuracy, as well as quantitative characterization of stenoses by three blinded readers. Correlations between readers of conventional angiograms were calculated and compared with MR results. RESULTS: In 174 patients, MS-325-enhanced MR angiography showed significant improvement (P < or = .001) in sensitivity, specificity, and accuracy for diagnosis of clinically significant (> or =50%) stenosis, compared with unenhanced MR. For all readers, areas under the receiver operating characteristic curve for both quantitative and qualitative measures of significant disease increased (P < .001) for MS-325-enhanced MR compared with time-of-flight MR. All readers also expressed higher confidence in diagnosis (P < .001) and found fewer images uninterpretable with MS-325 enhancement. All measures of interpretation accuracy approached corresponding measures of correlation between readers of conventional angiograms. Incidence of severe and serious adverse events with MS-325 was low. No patients were withdrawn from study due to adverse events or abnormalities in laboratory results. There were no clinically important trends in findings at hematology, blood chemistry, urinalysis, electrocardiography, or physical examination. CONCLUSION: MR angiography with MS-325 provides significant improvement in effectiveness over unenhanced MR (and minimal and transient side effects) at a dose of 0.03 mmol/kg and was safe and effective for MR evaluation of patients with aortoiliac occlusive disease.

Adult↗

PubMed2005

Conspicuity of liver hemangiomas: short tau inversion recovery, T1, and T2 imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid.

PURPOSE: To compare conspicuity of liver hemangiomas on STIR, T1-weighted, and T2-weighted magnetic resonance (MR) images before and after administration of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) (hepatocellular contrast agent), using contrast-to-noise ratios (CNRs). MATERIALS AND METHODS: Thirteen hemangiomas were imaged using breath-hold gradient echo (GRE) T1, fat-saturated turbo spin echo (TSE)-T2, and short tau inversion recovery (STIR) sequences. Background noise and signal-to-noise ratios (SNRs) for liver and hemangioma, along with CNR for normal liver and hemangioma, were measured on each sequence before and after administration of Gd-EOB-DTPA. Hemangioma conspicuity was also evaluated qualitatively. RESULTS: After Gd-EOB-DTPA administration, the quantitative liver SNR decreased 54% on STIR, increased 45% on T1-weighted images, and increased 14.5% on TSE-T2-weighted images. The CNR for liver and hemangioma increased 50% on STIR images (P < 0.0001), increased 46% on T1-weighted imaging (P = 0.0033), and increased 22% on TSE-T2-weighted MR imaging (MRI) (P = 0.0083). After contrast, the CNR for TSE-T2 images was greater than those for both the T1 and STIR images (P < 0.0001 for both). Qualitatively, signal change was visually apparent in the liver on T1 and STIR, but not on T2 images or in the hemangiomas on any sequence. CONCLUSION: Despite the statistically significant T1 and STIR increase in CNR, liver hemangiomas were most conspicuous on TSE-T2 images after Gd-EOB-DTPA. This pilot study with hemangiomas highlights the newly recognized potential benefit of TSE-T2 imaging with hepatocellular contrast.

Adult↗

PubMed2005

Aortoiliac occlusive disease in patients with known or suspected peripheral vascular disease: safety and efficacy of gadofosveset-enhanced MR angiography--multicenter comparative phase III study.

PURPOSE: To prospectively determine the safety and efficacy of the gadolinium-based blood pool magnetic resonance (MR) imaging contrast agent gadofosveset in patients known to have or suspected of having peripheral vascular disease. MATERIALS AND METHODS: Ethical committee approval and patient written informed consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. Adults known or suspected to have peripheral vascular disease received gadofosveset (0.03 mmol per kilogram of body weight) for MR angiography of the aortoiliac region. Gadofosveset-enhanced MR angiography and unenhanced two-dimensional time-of-flight MR angiography were compared with the reference standard, conventional angiography, for the presence of vascular stenosis. All patients were monitored for adverse events with hematologic analysis, analysis of blood chemistry, urinalysis, and electrocardiographic parameters; these methods were analyzed to determine safety. RESULTS: A total of 274 patients were enrolled at 37 centers. Gadofosveset-enhanced MR angiography showed significant improvement (P < .001) compared with unenhanced MR angiography for each of the readers for diagnosis of clinically significant (> or = 50%) stenosis. Specificity and accuracy were significantly greater for three readers, and sensitivity increased significantly for two readers. For all readers, the area under the receiver operator characteristic curve for both quantitative and qualitative measures of significant disease increased (P < .001) for gadofosveset-enhanced MR angiography versus two-dimensional time-of-flight MR angiography. All readers also expressed more confidence in diagnosis (P < .001) and found fewer images to be uninterpretable (0.5% vs 11.0%). The most common adverse events were as follows: feeling hot, 12 (4.4%) patients; nausea, 10 (3.6%) patients; headache, nine (3.3%) patients; and burning sensation, eight (2.9%) patients. Only four serious adverse events were reported, in three patients, and all events were rated as unlikely related to the drug. No patients were excluded because of adverse events or laboratory abnormalities. There were no clinically important trends in the findings of hematologic analysis, blood chemistry, urinalysis, electrocardiography, or physical examination. CONCLUSION: On the basis of substantial improvements over non-contrast MR angiography in efficacy and a minimal and transient side-effect profile, gadofosveset was found to be safe and effective for MR angiography in patients known or suspected to have peripheral vascular disease.

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PubMed2004

MR coronary angiography with SH L 643 A: initial experience in patients with coronary artery disease.

PURPOSE: To prospectively assess the accuracy of breath-hold three-dimensional magnetic resonance (MR) coronary angiography with the gadolinium-based intravascular contrast agent SH L 643 A in patients with coronary artery disease. MATERIALS AND METHODS: Twelve patients (seven men, five women; age range, 46-78 years; mean age, 61.3 years) with angiographically proved coronary artery disease (luminal narrowing >50%) underwent breath-hold three-dimensional MR coronary angiography before and after injection of SH L 643 A (0.1 mmol gadolinium per kilogram body weight). For all MR examinations, signal-to-noise ratio and contrast-to-noise ratio were measured. Image quality was assessed with a four-point scale. Conventional angiograms and MR angiograms were evaluated for depiction of the left main, proximal and middle left anterior descending, proximal left circumflex, and proximal and middle right coronary artery segments in a blinded fashion by two experienced readers in consensus. Results of this evaluation were compared by using a paired Student t test. P < .05 was considered to indicate a statistically significant difference. RESULTS: For the 72 coronary artery segments, the contrast-to-noise ratio significantly improved after administration of SH L 643 A, compared with the prior ratio (9.8 +/- 5.1 [standard deviation] vs 23.0 +/- 8.7; P < .01), whereas the difference in signal-to-noise ratio did not reach statistical significance (25.2 +/- 11.4 vs 29.5 +/- 9.8; P > .3). Image quality significantly improved from a mean of 2.0 +/- 0.9 for nonenhanced images to 2.9 +/- 0.9 (P < .03) for contrast material-enhanced images. The proportion of segments for which images were nondiagnostic decreased from 38% to 10% with application of SH L 643 A. Overall sensitivity and specificity of contrast-enhanced MR coronary angiography for detection of coronary artery disease were 80% and 93%, respectively, and accuracy was 87%. CONCLUSION: Use of SH L 643 A improves detection of coronary artery disease at three-dimensional MR coronary angiography.

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PubMed2003

MR angiography with gadofosveset trisodium for peripheral vascular disease: phase II trial.

PURPOSE: To evaluate the dose response and safety of gadofosveset trisodium-enhanced magnetic resonance (MR) angiography compared with nonenhanced two-dimensional time-of-flight MR angiography and with x-ray angiography as the standard. MATERIALS AND METHODS: In this randomized, 20-center, double-blind study, 238 men and women who had peripheral vascular disease or were suspected of having it received intravenous injection of placebo or gadofosveset (0.005, 0.01, 0.03, 0.05, or 0.07 mmol per kilogram of body weight). MR angiographic images were evaluated by three blinded readers, and x-ray angiographic images were evaluated by two readers. Hypothesis testing for the presence of a dose response was based on a linear test for trend for increase in area under the receiver operating characteristic curve as a function of dose for each reader of MR angiographic images independently. RESULTS: Gadofosveset administration resulted in a dose-dependent increase in diagnostic accuracy for detection of aortoiliac occlusive disease as reflected in the area under the receiver operating characteristic curve for each reader (P <.001). The plateau in effectiveness improvement began at the 0.03 mmol/kg dose. At doses of 0.03 mmol/kg and higher, gadofosveset-enhanced MR angiography provided an approximate 20% increase in accuracy over nonenhanced MR angiography for diagnosis of clinically significant aortoiliac occlusive disease. Gadofosveset exhibited a good safety profile in all dose groups. Three serious adverse events were possibly or probably related to gadofosveset administration. There were no dose-related trends in severe or serious adverse events in patients receiving gadofosveset. CONCLUSION: A dose of 0.03 mmol/kg of gadofosveset was safe and effective for evaluation of aortoiliac occlusive disease with MR angiography.

Adult↗

PubMed2003

Coronary arteries: contrast-enhanced MR imaging with SH L 643A--experience in 12 volunteers.

PURPOSE: To assess SH L 643A for three-dimensional breath-hold and respiratory-gated magnetic resonance (MR) imaging in the depiction of coronary arteries. MATERIALS AND METHODS: Twelve healthy male volunteers underwent either three-dimensional breath-hold (n = 6) or respiratory-gated (n = 6) coronary MR angiography before and after intravenous injection of 0.1 mmol SH L 643A per kilogram of body weight. For nonenhanced and contrast material-enhanced examinations, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements were obtained. Image quality was assessed in consensus with a five-point scale. Statistical analysis of nonenhanced and contrast-enhanced images was based on a two-tailed paired Student t test. A P value at the.05 significance level was used. RESULTS: Overall statistically significant improvement in CNR was observed after administration of SH L 643A compared with that on nonenhanced images (8.7 +/- 5.3 [SD] vs 23.6 +/- 7.2, P <.01). While SNR of contrast-enhanced images showed improvement over that of nonenhanced images, the difference was not statistically significant (25.4 +/- 0.8 vs 30.2 +/- 16.8, P >.2). Image quality improved from a mean of 3.1 +/- 0.8 for nonenhanced images to 4.0 +/- 0.8 (P <.01) for contrast-enhanced images. CONCLUSION: SH L 643A causes significant improvement of the blood-myocardium contrast enhancement at coronary MR angiography compared with that with nonenhanced sequences.

Adult↗

PubMed2002

Preoperative evaluation of malignant liver tumors: comparison of unenhanced and SPIO (Resovist)-enhanced MR imaging with biphasic CTAP and intraoperative US.

The purpose of this study was to evaluate the diagnostic efficacy of iron-oxide-enhanced MRI vs CT during arterial portography (CTAP) and intraoperative ultrasound (IOUS) in detection of liver neoplasms. Seventeen patients with malignant focal liver lesions (liver metastases, n=7), hepatocellular carcinomas (HCC, n=9), and cholangiocellular carcinoma (CCC, n=1) underwent presurgical Resovist-enhanced MRI and CTAP. Two independent observers (A and B) assessed the blinded images of unenhanced and iron-oxide-enhanced MRI vs CTAP for the presence, number, and location of the liver lesions. These results were compared lesion by lesion and segment by segment with the results of intraoperative ultrasound ( n=17) serving as the reference standard. Eighty lesions were detected by intraoperative ultrasound in 17 patients. In comparison with IOUS (lesion-by-lesion analysis) the sensitivity was 86.8% for CTAP, 65% for combined unenhanced MR imaging, and 86.8% for combined Resovist-enhanced MRI as well as 86.8% for the combination of unenhanced and Resovist-enhanced MRI. Compared with the sensitivity of combined unenhanced MRI the sensitivity of CTAP as well as the sensitivity of combined Resovist-enhanced MRI was significantly higher (p<0.05). False-positive results were much higher in CTAP as compared with combined unenhanced and SPIO-enhanced MRI. Using the segment-by-segment analysis the specificity of combined unenhanced MRI with 100% (96.7-100%) as well as combined Resovist-enhanced MRI with 100% (96.7-100%) was significantly higher (p<0.05) in comparison with the specificity of CTAP with 91.1% (83.2-96.1%). The accuracy of combined unenhanced MRI was 100% (93.2-100%), combined Resovist-enhanced MRI 100% (93.6-100%) and of CTAP 85.2% (72.9-93.4%). In the detection of focal liver lesions iron-oxide-enhanced MR imaging is superior to unenhanced MRI and similar to CTAP.

Adult↗