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Novel serine palmitoyl transferase inhibitor mitigates contrast-induced nephropathy
S106
’
Tuesday
Scientific Session
Conclusion: Our initial results demonstrate that indexed splenic arterial and venous flow increases dramatically in splenomegaly, far above what would be expected from increases in splenic size alone. This relationship suggests a hemodynamic etiology for hypersplenism-associated thrombocytopenia. Quantification of splenic hemodynamics at 4D flow MRI may be useful in the triage of patients referred for partial splenic embolization.
3:39 PM
Abstract No. 227
Interventional optical molecular imaging for percutaneous liver procedures: initial clinical trial results
TUESDAY: Scientific Sessions
R. Sheth, R. Arellano, A. Samir, S. Ganguli, R. Oklu, A. Zhu, D.A., Gervais U. Mahmood; Massachusetts General Hospital, Boston, MA Purpose: To demonstrate the clinical value of a point-of-care, hand-held optical molecular imaging (OMI) platform for the localization of focal hepatic lesions during percutaneous hepatic interventions. Materials and Methods: Patients with suspected hepatocellular carcinoma or liver metastases from colorectal cancer scheduled for percutaneous liver biopsy or thermal ablation were eligible for this study. Indocyanine green (ICG) at 0.5 mg/ kg was administered intravenously 24 hours prior to their scheduled procedure in this prospective, IRB-approved, HIPAA-compliant prospective study. Intraprocedurally, a handheld device composed of an endoscope that fits coaxially through a standard 17 gauge introducer needle was advanced into the liver, and real-time measurements of ICG fluorescence were obtained. A point-of-care fluorescence imaging system was used to image ICG fluorescence within biopsy samples. Results: Intraprocedural OMI was successfully performed on 7 lesions in 6 patients, including 6 biopsy procedures and 2 ablation procedures (one lesion underwent both biopsy and ablation). The median size of the targeted lesions was 16mm (range 10-21mm). Five of 6 biopsies (83%) yielded an accurate pathologic diagnosis, and 1 biopsy showed benign liver parenchyma; both ablated lesions showed no residual disease 1 month after the procedure. The median overall added procedure time to perform OMI was 2 minutes. ICG was found to localize with high target to background ratios (median 7.9, range 2.4 - 13.4) in all target lesions. No trial-related adverse events were reported. Conclusion: We demonstrate the clinical translation of OMI to percutaneous hepatic interventions. Real-time intraprocedural OMI may complement current imaging techniques to improve the accuracy of lesion localization during percutaneous interventions, thereby reducing false negative biopsies and improving margin definition during thermal ablations.
3:48 PM
Abstract No. 228
Novel serine palmitoyl transferase inhibitor mitigates contrast-induced nephropathy M. Naeem, V. Frank, G. Baird, T.P. Murphy, W.K. Park; Diagnostic Imaging, Brown University/ Rhode Island Hospital, Providence, RI
’
JVIR
Purpose: De novo ceramide synthesis is one of the mechanism of cell death in contrast-induced nephropathy. We hereby present our preliminary data regarding the novel inhibitor of serine palmitoyltransferase inhibitor (SPTi), rate limiting enzyme in denovo ceramide synthesis, in protecting renal epithelial cells against contrast-mediated injury. Materials and Methods: Iohexol was diluted to prepare concentrations of 100, 200 and 300 mg iodine/ml and the cultured renal epithelial cells (HEK-293 and LLC-PK1) were exposed in vitro for different time periods (90,120,720 and 1440 mins) against the above mentioned concentrations. Apoptotic assays were done to assess cell death by measuring Bax, a proapoptotic molecule. Myriocin, a commercially available SPT inhibitor, and our novel SPTi were used to assess their relative efficacies in preserving cell viability. Cell death was measured by using WST-8 assay at 620nm and 450 nm absorbance. For all experiments, the differences of optical density 450-620 (ODdiff) were modeled using generalized Estimating Equation with classic sandwich estimation, where observations were nested by slides. All multiple comparison were conducted using Bonferroni correction and alpha ¼.05 for all analyses. Results: Between 120 and 720 minutes, significant cell death was observed for 100mg (p¼.0072), 200mg (po.0001) and 300 mg (po.0001). The mechanism of cell death was apoptosis as evident by increase expression of Bax, a proapoptotic molecule. On repeated experiments with 2 nmol Myriocin, we found that Myriocin was unable to rescue the cells as compared to no Myriocin (p¼.999). No difference was detected between the two: controls without Myriocin and the Myriocin treatment, with the exception of 100mg Iohexol concentration which revealed a significant decrease in cell death relative to controls (p¼ 0.0159 and p¼0.0011). As SPT inhibitor dose increased, cell death decreased. At 30micromol SPT concentration, cell death was significantly less than at 1 micromol (po.0001), and approached significance compared with no drug for all SPT concentrations (p¼.08) Conclusion: The novel SPTi molecule significantly mitigates renal tubule epithelial cell death after exposure to iodinated contrast media.
3:57 PM
Abstract No. 229
Feasibility of a semi-automatic, model-based segmentation software for diseased livers R.E. Schernthaner1, R. Ardon2, R. Duran1, S. Sahu1, J. Sohn1, J.H. Geschwind1, M. Lin3; 1Radiology, The Johns Hopkins Hospital, Baltimore, MD; 2Philips Medisys, Suresnes, France; 3U/S Imaging and Interventions (UII), Philips Research North American, Briarcliff Manor, NY Purpose: Accurate liver segmentation has several clinical applications, e.g. the assessment of liver growth after portal vein embolization. However, using the applications currently available is often time-consuming, limiting their applicability in daily clinical practice. Thus, a semi-automatic software prototype was developed that consists of an automatic first pass based on an anatomical liver model, with a second pass process that allows for semi-automatic modification. The purpose of this study was to evaluate the feasibility of this prototype. Materials and Methods: 25 hepatocellular carcinoma patients with underlying cirrhosis were included. A radiologist
’
Tuesday
Scientific Session
Conclusion: Our initial results demonstrate that indexed splenic arterial and venous flow increases dramatically in splenomegaly, far above what would be expected from increases in splenic size alone. This relationship suggests a hemodynamic etiology for hypersplenism-associated thrombocytopenia. Quantification of splenic hemodynamics at 4D flow MRI may be useful in the triage of patients referred for partial splenic embolization.
3:39 PM
Abstract No. 227
Interventional optical molecular imaging for percutaneous liver procedures: initial clinical trial results
TUESDAY: Scientific Sessions
R. Sheth, R. Arellano, A. Samir, S. Ganguli, R. Oklu, A. Zhu, D.A., Gervais U. Mahmood; Massachusetts General Hospital, Boston, MA Purpose: To demonstrate the clinical value of a point-of-care, hand-held optical molecular imaging (OMI) platform for the localization of focal hepatic lesions during percutaneous hepatic interventions. Materials and Methods: Patients with suspected hepatocellular carcinoma or liver metastases from colorectal cancer scheduled for percutaneous liver biopsy or thermal ablation were eligible for this study. Indocyanine green (ICG) at 0.5 mg/ kg was administered intravenously 24 hours prior to their scheduled procedure in this prospective, IRB-approved, HIPAA-compliant prospective study. Intraprocedurally, a handheld device composed of an endoscope that fits coaxially through a standard 17 gauge introducer needle was advanced into the liver, and real-time measurements of ICG fluorescence were obtained. A point-of-care fluorescence imaging system was used to image ICG fluorescence within biopsy samples. Results: Intraprocedural OMI was successfully performed on 7 lesions in 6 patients, including 6 biopsy procedures and 2 ablation procedures (one lesion underwent both biopsy and ablation). The median size of the targeted lesions was 16mm (range 10-21mm). Five of 6 biopsies (83%) yielded an accurate pathologic diagnosis, and 1 biopsy showed benign liver parenchyma; both ablated lesions showed no residual disease 1 month after the procedure. The median overall added procedure time to perform OMI was 2 minutes. ICG was found to localize with high target to background ratios (median 7.9, range 2.4 - 13.4) in all target lesions. No trial-related adverse events were reported. Conclusion: We demonstrate the clinical translation of OMI to percutaneous hepatic interventions. Real-time intraprocedural OMI may complement current imaging techniques to improve the accuracy of lesion localization during percutaneous interventions, thereby reducing false negative biopsies and improving margin definition during thermal ablations.
3:48 PM
Abstract No. 228
Novel serine palmitoyl transferase inhibitor mitigates contrast-induced nephropathy M. Naeem, V. Frank, G. Baird, T.P. Murphy, W.K. Park; Diagnostic Imaging, Brown University/ Rhode Island Hospital, Providence, RI
’
JVIR
Purpose: De novo ceramide synthesis is one of the mechanism of cell death in contrast-induced nephropathy. We hereby present our preliminary data regarding the novel inhibitor of serine palmitoyltransferase inhibitor (SPTi), rate limiting enzyme in denovo ceramide synthesis, in protecting renal epithelial cells against contrast-mediated injury. Materials and Methods: Iohexol was diluted to prepare concentrations of 100, 200 and 300 mg iodine/ml and the cultured renal epithelial cells (HEK-293 and LLC-PK1) were exposed in vitro for different time periods (90,120,720 and 1440 mins) against the above mentioned concentrations. Apoptotic assays were done to assess cell death by measuring Bax, a proapoptotic molecule. Myriocin, a commercially available SPT inhibitor, and our novel SPTi were used to assess their relative efficacies in preserving cell viability. Cell death was measured by using WST-8 assay at 620nm and 450 nm absorbance. For all experiments, the differences of optical density 450-620 (ODdiff) were modeled using generalized Estimating Equation with classic sandwich estimation, where observations were nested by slides. All multiple comparison were conducted using Bonferroni correction and alpha ¼.05 for all analyses. Results: Between 120 and 720 minutes, significant cell death was observed for 100mg (p¼.0072), 200mg (po.0001) and 300 mg (po.0001). The mechanism of cell death was apoptosis as evident by increase expression of Bax, a proapoptotic molecule. On repeated experiments with 2 nmol Myriocin, we found that Myriocin was unable to rescue the cells as compared to no Myriocin (p¼.999). No difference was detected between the two: controls without Myriocin and the Myriocin treatment, with the exception of 100mg Iohexol concentration which revealed a significant decrease in cell death relative to controls (p¼ 0.0159 and p¼0.0011). As SPT inhibitor dose increased, cell death decreased. At 30micromol SPT concentration, cell death was significantly less than at 1 micromol (po.0001), and approached significance compared with no drug for all SPT concentrations (p¼.08) Conclusion: The novel SPTi molecule significantly mitigates renal tubule epithelial cell death after exposure to iodinated contrast media.
3:57 PM
Abstract No. 229
Feasibility of a semi-automatic, model-based segmentation software for diseased livers R.E. Schernthaner1, R. Ardon2, R. Duran1, S. Sahu1, J. Sohn1, J.H. Geschwind1, M. Lin3; 1Radiology, The Johns Hopkins Hospital, Baltimore, MD; 2Philips Medisys, Suresnes, France; 3U/S Imaging and Interventions (UII), Philips Research North American, Briarcliff Manor, NY Purpose: Accurate liver segmentation has several clinical applications, e.g. the assessment of liver growth after portal vein embolization. However, using the applications currently available is often time-consuming, limiting their applicability in daily clinical practice. Thus, a semi-automatic software prototype was developed that consists of an automatic first pass based on an anatomical liver model, with a second pass process that allows for semi-automatic modification. The purpose of this study was to evaluate the feasibility of this prototype. Materials and Methods: 25 hepatocellular carcinoma patients with underlying cirrhosis were included. A radiologist