MRI plays a major role in follow-up of patients with malignant bone tumors. However, after limb s... more MRI plays a major role in follow-up of patients with malignant bone tumors. However, after limb salvage surgery, orthopaedic tumor endoprostheses might cause significant metal-induced susceptibility artifacts. To evaluate the benefit of view-angle tilting (VAT) and slice-encoding metal artifact correction (SEMAC) for MRI of large-sized orthopaedic tumor endoprostheses in an experimental model and to demonstrate clinical benefits for assessment of periprosthetic soft tissue abnormalities. In an experimental setting, tumor endoprostheses (n=4) were scanned at 1.5T with three versions of optimized high-bandwidth turbo-spin-echo pulse sequences: (i) standard, (ii) VAT and (iii) combined VAT and SEMAC (VAT&SEMAC). Pulse sequences included coronal short-tau-inversion-recovery (STIR), coronal T1-weighted (w), transverse T1-w and T2-w TSE sequences. For clinical evaluation, VAT&SEMAC was compared to conventional metal artifact-reducing MR sequences (conventional MR) in n=25 patients with metal implants and clinical suspicion of tumor recurrence or infection. Diameters of artifacts were measured quantitatively. Qualitative parameters were assessed on a five-point scale (1=best, 5=worst): "image distortion", "artificial signal changes at the edges" and "diagnostic confidence". Imaging findings were correlated with pathology. T-tests and Wilcoxon-signed rank tests were used for statistical analyses. The true size of the prostheses was overestimated on MRI (P<0.05). A significant reduction of artifacts was achieved by VAT (P<0.001) and VAT&SEMAC (P=0.003) compared to the standard group. Quantitative scores improved in the VAT and VAT&SEMAC group (P<0.05). On clinical MR images, artifact diameters were significantly reduced in the VAT&SEMAC-group as compared with the conventional-group…
The objective of this study was to investigate the improvement in diagnostic quality of an iterat... more The objective of this study was to investigate the improvement in diagnostic quality of an iterative model-based reconstruction (IMBR) algorithm for low-tube-voltage (80-kVp) and low-tube-current in abdominal computed tomography angiography (CTA). A total of 11 patients were imaged on a 256-slice multidetector computed tomography for visualization of the aorta. For all patients, three different reconstructions from the low-tube-voltage data are generated: filtered backprojection (FBP), IMBR, and a mixture of both [Formula: see text]. To determine the diagnostic value of IMBR-based reconstructions, the image quality was assessed. With IMBR-based reconstructions, image noise could be significantly reduced, which was confirmed by a highly improved contrast-to-noise ratio. In the image quality assessment, radiologists were able to reliably detect more third-order and higher aortic branches in the IMBR reconstructions compared to FBP reconstructions. The effective dose level was, on average, 3.0 mSv for 80-kVp acquisitions. Low-tube-voltage CTAs significantly improve vascular contrast as presented by others; however, this effect in combination with IMBR enabled yet another substantial improvement of diagnostic quality. For IMBR, a significant improvement of image quality and a decreased radiation dose at low-tube-voltage can be reported.
To evaluate quantitative perfusion measurements of dynamic indocyanine green (ICG)-enhanced optic... more To evaluate quantitative perfusion measurements of dynamic indocyanine green (ICG)-enhanced optical imaging for monitoring synovitis in the hands of patients with inflammatory arthritis compared with dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and clinical outcome. This study was approved by the ethics committee at the institution. Individual joints (n = 840) in the hands and wrists of 28 patients (14 women; mean age, 53.3 years) with inflammatory arthritis were examined at three different time points: before start of therapy and 12 and 24 weeks after start of therapy or therapy escalation. Treatment response was assessed by using clinical measures (simple disease activity index [SDAI]), ICG-enhanced optical imaging, and DCE MR imaging. Dynamic images were obtained for optical imaging and DCE MR imaging. The rate of early enhancement (REE) of the perfusion curves of each joint was calculated by using in-house developed software. Correlation coefficients were estimated to evaluate the associations of changes of imaging parameters and SDAI change. Quantitative perfusion measurements with optical imaging and MR imaging correctly identified patients who responded (n = 18) and did not respond to therapy (n = 10), as determined by SDAI. The difference of REE after 24 weeks of treatment compared with baseline in responders was significantly reduced in optical imaging and MR imaging (optical imaging: mean, -21.5%; MR imaging: mean, -41.0%; P < .001 for both), while in nonresponders it was increased (optical imaging: mean, 10.8%; P = .075; MR imaging: mean, 8.7%; P = .03). The REE of optical imaging significantly correlated with MR imaging (ρ = 0.80; P < .001) and SDAI (ρ = 0.61; P < .001). Quantitative analysis of contrast-enhanced optical imaging allows for potential therapeutic monitoring of synovitis in patients with inflammatory arthritis.
To assess the capability of the folate receptor (FR)-targeted ultrasmall superparamagnetic iron o... more To assess the capability of the folate receptor (FR)-targeted ultrasmall superparamagnetic iron oxide (USPIO) P1133 to provide FR-specific enhancement of breast cancers on magnetic resonance (MR) images. This study was approved by the institutional Animal Care and Use Committee. The FR-targeted contrast agent P1133 was incubated with various FR-positive human breast cancer cell lines, with and without free folic acid (FFA) as a competitor. Labeling efficiencies were evaluated with MR imaging and inductively coupled plasma mass spectrometry. Subsequently, six athymic rats with implanted FR-positive MDA-MB-231 breast cancers underwent MR imaging at 3 T before and up to 1 hour and 24 hours after injection of P1133. Six athymic rats with implanted FR-positive MDA-MB-231 cancers injected with the non-FR-targeted USPIO P904 and nine athymic rats with implanted FR-negative A549 lung cancers injected with P1133 (n = 6) or P904 (n = 3) served as controls. Data of the in vitro studies were compared for significant differences with the Wilcoxon test for two independent samples. Tumor signal-to-noise-ratios (SNRs) were compared between different experimental groups by using the Kruskal-Wallis test and were correlated with histopathologic findings. Differences with P < .05 were considered significant. FR-positive breast cancer cells showed a significant P1133 uptake which was inhibited by FFA. MDA-MB-231 cells showed the highest level of P1133 uptake and the strongest T2 effect on MR images. In vivo, all tumors showed an initial perfusion effect. At 24 hours after injection, only MDA-MB-231 tumors injected with P1133 showed significantly decreased SNR data compared with baseline data (P < .05). MR findings were confirmed by using histopathologic findings. The FR-targeted USPIO P1133 demonstrates a specific retention in FR-positive breast cancers. Because FR expression correlates with tumor aggressiveness and prognosis, persistent P1133 tumor enhancement may be used as a noninvasive indicator for tumors with poor outcome.
Genetically modified natural killer (NK) cells that recognize tumor-associated surface antigens h... more Genetically modified natural killer (NK) cells that recognize tumor-associated surface antigens have recently shown promise as a novel approach for cancer immunotherapy. To determine NK cell therapy response early, a real-time, noninvasive method to quantify NK cell homing to the tumor is desirable. The purpose of this study was to evaluate if MR imaging could provide a noninvasive, in vivo diagnosis of NK cell accumulation in epithelial cell adhesion molecule (EpCAM)-positive prostate cancers in a rat xenograft model. Genetically engineered NK-92-scFv(MOC31)-ζ cells, which express a chimeric antigen receptor specific to the tumor-associated EpCAM antigen, and nontargeted NK-92 cells were labeled with superparamagnetic particles of iron-oxides (SPIO) ferumoxides. Twelve athymic rats with implanted EpCAM positive DU145 prostate cancers received intravenous injections of 1.5×10(7) SPIO labeled NK-92 and NK-92-scFv(MOC31)-ζ cells. EpCAM-positive prostate cancers demonstrated a progressive and a significant decline in contrast-to-noise-ratio data at 1 and 24 h after injection of SPIO-labeled NK-92-scFv(MOC31)-ζ cells. Conversely, tumor contrast-to-noise-ratio data did not change significantly after injection of SPIO-labeled parental NK-92 cells. Histopathology confirmed an accumulation of the genetically engineered NK-92-scFv(MOC31)-ζ cells in prostate cancers. Thus, the presence or absence of a tumor accumulation of therapeutic NK cells can be monitored with cellular MR imaging. EpCAM-directed, SPIO labeled NK-92-scFv(MOC31)-ζ cells accumulate in EpCAM-positive prostate cancers.
To compare a 256-slice CT with a simulated standard CT for brain CT perfusion (CTP). CTP was obta... more To compare a 256-slice CT with a simulated standard CT for brain CT perfusion (CTP). CTP was obtained in 51 patients using a 256-slice CT (128 detector rows, flying z-focus, 8-cm detector width, 80 kV, 120mAs, 20 measurements, 1 CT image/2.5 s). Signal-to-noise ratios (SNR) were compared in grey and white matter. Perfusion maps were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in hypoperfused areas and corresponding contralateral regions. Two reconstructed 10-mm slices for simulation of a standard CT (SDCT) were compared with the complete data sets (large-volume CT, LVCT). Adequate image quality was achieved in 50/51 cases. SNR were significantly different in grey and white matter. A perfusion deficit was present in 27 data sets. Differences between the hypoperfusions and the control regions were significant for MTT and CBF, but not for CBV. Three lesions were missed by SDCT but detected by LVCT; 24 lesions were covered incompletely by SDCT, and 6 by LVCT. 21 lesions were detected completely by LVCT, but none by SDCT. CTP imaging of the brain using an increased detector width can detect additional ischaemic lesions and cover most ischaemic lesions completely.
PURPOSE To investigate Annexin V targeted molecular imaging of cardiomyocyte apoptosis in the ear... more PURPOSE To investigate Annexin V targeted molecular imaging of cardiomyocyte apoptosis in the early course after murine myocardial infarction. METHOD AND MATERIALS Myocardial infarction (MI) was induced in Kit+/+ mice by 30 minutes ligation of the left anterior descending artery (LAD) with subsequent reperfusion. Mice were injected with the Annexin V targeted molecular imaging probe Annexin-Vivo750 4 hours prior to imaging. Additionally mice were injected with a long-circulating iodine-based contrast agent (Exitron 12000) prior to imaging for better visualization of cardiac anatomy with subsequent facilitated organ segmentation. Hybrid FMT-XCT was performed 6 hours, 24 hours and 7 days after induction of ischemic injury. Molecular imaging signal for Annexin-Vivo750 was validated by ex-vivo immunohistochemistry and flow cytometry. RESULTS Successful image acquisition of both FMT and CT angiography was achieved in all mice. Molecular imaging signal for Annexin-Vivo750 could be localiz...
MRI plays a major role in follow-up of patients with malignant bone tumors. However, after limb s... more MRI plays a major role in follow-up of patients with malignant bone tumors. However, after limb salvage surgery, orthopaedic tumor endoprostheses might cause significant metal-induced susceptibility artifacts. To evaluate the benefit of view-angle tilting (VAT) and slice-encoding metal artifact correction (SEMAC) for MRI of large-sized orthopaedic tumor endoprostheses in an experimental model and to demonstrate clinical benefits for assessment of periprosthetic soft tissue abnormalities. In an experimental setting, tumor endoprostheses (n=4) were scanned at 1.5T with three versions of optimized high-bandwidth turbo-spin-echo pulse sequences: (i) standard, (ii) VAT and (iii) combined VAT and SEMAC (VAT&SEMAC). Pulse sequences included coronal short-tau-inversion-recovery (STIR), coronal T1-weighted (w), transverse T1-w and T2-w TSE sequences. For clinical evaluation, VAT&SEMAC was compared to conventional metal artifact-reducing MR sequences (conventional MR) in n=25 patients with metal implants and clinical suspicion of tumor recurrence or infection. Diameters of artifacts were measured quantitatively. Qualitative parameters were assessed on a five-point scale (1=best, 5=worst): "image distortion", "artificial signal changes at the edges" and "diagnostic confidence". Imaging findings were correlated with pathology. T-tests and Wilcoxon-signed rank tests were used for statistical analyses. The true size of the prostheses was overestimated on MRI (P<0.05). A significant reduction of artifacts was achieved by VAT (P<0.001) and VAT&SEMAC (P=0.003) compared to the standard group. Quantitative scores improved in the VAT and VAT&SEMAC group (P<0.05). On clinical MR images, artifact diameters were significantly reduced in the VAT&SEMAC-group as compared with the conventional-group…
The objective of this study was to investigate the improvement in diagnostic quality of an iterat... more The objective of this study was to investigate the improvement in diagnostic quality of an iterative model-based reconstruction (IMBR) algorithm for low-tube-voltage (80-kVp) and low-tube-current in abdominal computed tomography angiography (CTA). A total of 11 patients were imaged on a 256-slice multidetector computed tomography for visualization of the aorta. For all patients, three different reconstructions from the low-tube-voltage data are generated: filtered backprojection (FBP), IMBR, and a mixture of both [Formula: see text]. To determine the diagnostic value of IMBR-based reconstructions, the image quality was assessed. With IMBR-based reconstructions, image noise could be significantly reduced, which was confirmed by a highly improved contrast-to-noise ratio. In the image quality assessment, radiologists were able to reliably detect more third-order and higher aortic branches in the IMBR reconstructions compared to FBP reconstructions. The effective dose level was, on average, 3.0 mSv for 80-kVp acquisitions. Low-tube-voltage CTAs significantly improve vascular contrast as presented by others; however, this effect in combination with IMBR enabled yet another substantial improvement of diagnostic quality. For IMBR, a significant improvement of image quality and a decreased radiation dose at low-tube-voltage can be reported.
To evaluate quantitative perfusion measurements of dynamic indocyanine green (ICG)-enhanced optic... more To evaluate quantitative perfusion measurements of dynamic indocyanine green (ICG)-enhanced optical imaging for monitoring synovitis in the hands of patients with inflammatory arthritis compared with dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and clinical outcome. This study was approved by the ethics committee at the institution. Individual joints (n = 840) in the hands and wrists of 28 patients (14 women; mean age, 53.3 years) with inflammatory arthritis were examined at three different time points: before start of therapy and 12 and 24 weeks after start of therapy or therapy escalation. Treatment response was assessed by using clinical measures (simple disease activity index [SDAI]), ICG-enhanced optical imaging, and DCE MR imaging. Dynamic images were obtained for optical imaging and DCE MR imaging. The rate of early enhancement (REE) of the perfusion curves of each joint was calculated by using in-house developed software. Correlation coefficients were estimated to evaluate the associations of changes of imaging parameters and SDAI change. Quantitative perfusion measurements with optical imaging and MR imaging correctly identified patients who responded (n = 18) and did not respond to therapy (n = 10), as determined by SDAI. The difference of REE after 24 weeks of treatment compared with baseline in responders was significantly reduced in optical imaging and MR imaging (optical imaging: mean, -21.5%; MR imaging: mean, -41.0%; P < .001 for both), while in nonresponders it was increased (optical imaging: mean, 10.8%; P = .075; MR imaging: mean, 8.7%; P = .03). The REE of optical imaging significantly correlated with MR imaging (ρ = 0.80; P < .001) and SDAI (ρ = 0.61; P < .001). Quantitative analysis of contrast-enhanced optical imaging allows for potential therapeutic monitoring of synovitis in patients with inflammatory arthritis.
To assess the capability of the folate receptor (FR)-targeted ultrasmall superparamagnetic iron o... more To assess the capability of the folate receptor (FR)-targeted ultrasmall superparamagnetic iron oxide (USPIO) P1133 to provide FR-specific enhancement of breast cancers on magnetic resonance (MR) images. This study was approved by the institutional Animal Care and Use Committee. The FR-targeted contrast agent P1133 was incubated with various FR-positive human breast cancer cell lines, with and without free folic acid (FFA) as a competitor. Labeling efficiencies were evaluated with MR imaging and inductively coupled plasma mass spectrometry. Subsequently, six athymic rats with implanted FR-positive MDA-MB-231 breast cancers underwent MR imaging at 3 T before and up to 1 hour and 24 hours after injection of P1133. Six athymic rats with implanted FR-positive MDA-MB-231 cancers injected with the non-FR-targeted USPIO P904 and nine athymic rats with implanted FR-negative A549 lung cancers injected with P1133 (n = 6) or P904 (n = 3) served as controls. Data of the in vitro studies were compared for significant differences with the Wilcoxon test for two independent samples. Tumor signal-to-noise-ratios (SNRs) were compared between different experimental groups by using the Kruskal-Wallis test and were correlated with histopathologic findings. Differences with P < .05 were considered significant. FR-positive breast cancer cells showed a significant P1133 uptake which was inhibited by FFA. MDA-MB-231 cells showed the highest level of P1133 uptake and the strongest T2 effect on MR images. In vivo, all tumors showed an initial perfusion effect. At 24 hours after injection, only MDA-MB-231 tumors injected with P1133 showed significantly decreased SNR data compared with baseline data (P < .05). MR findings were confirmed by using histopathologic findings. The FR-targeted USPIO P1133 demonstrates a specific retention in FR-positive breast cancers. Because FR expression correlates with tumor aggressiveness and prognosis, persistent P1133 tumor enhancement may be used as a noninvasive indicator for tumors with poor outcome.
Genetically modified natural killer (NK) cells that recognize tumor-associated surface antigens h... more Genetically modified natural killer (NK) cells that recognize tumor-associated surface antigens have recently shown promise as a novel approach for cancer immunotherapy. To determine NK cell therapy response early, a real-time, noninvasive method to quantify NK cell homing to the tumor is desirable. The purpose of this study was to evaluate if MR imaging could provide a noninvasive, in vivo diagnosis of NK cell accumulation in epithelial cell adhesion molecule (EpCAM)-positive prostate cancers in a rat xenograft model. Genetically engineered NK-92-scFv(MOC31)-ζ cells, which express a chimeric antigen receptor specific to the tumor-associated EpCAM antigen, and nontargeted NK-92 cells were labeled with superparamagnetic particles of iron-oxides (SPIO) ferumoxides. Twelve athymic rats with implanted EpCAM positive DU145 prostate cancers received intravenous injections of 1.5×10(7) SPIO labeled NK-92 and NK-92-scFv(MOC31)-ζ cells. EpCAM-positive prostate cancers demonstrated a progressive and a significant decline in contrast-to-noise-ratio data at 1 and 24 h after injection of SPIO-labeled NK-92-scFv(MOC31)-ζ cells. Conversely, tumor contrast-to-noise-ratio data did not change significantly after injection of SPIO-labeled parental NK-92 cells. Histopathology confirmed an accumulation of the genetically engineered NK-92-scFv(MOC31)-ζ cells in prostate cancers. Thus, the presence or absence of a tumor accumulation of therapeutic NK cells can be monitored with cellular MR imaging. EpCAM-directed, SPIO labeled NK-92-scFv(MOC31)-ζ cells accumulate in EpCAM-positive prostate cancers.
To compare a 256-slice CT with a simulated standard CT for brain CT perfusion (CTP). CTP was obta... more To compare a 256-slice CT with a simulated standard CT for brain CT perfusion (CTP). CTP was obtained in 51 patients using a 256-slice CT (128 detector rows, flying z-focus, 8-cm detector width, 80 kV, 120mAs, 20 measurements, 1 CT image/2.5 s). Signal-to-noise ratios (SNR) were compared in grey and white matter. Perfusion maps were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in hypoperfused areas and corresponding contralateral regions. Two reconstructed 10-mm slices for simulation of a standard CT (SDCT) were compared with the complete data sets (large-volume CT, LVCT). Adequate image quality was achieved in 50/51 cases. SNR were significantly different in grey and white matter. A perfusion deficit was present in 27 data sets. Differences between the hypoperfusions and the control regions were significant for MTT and CBF, but not for CBV. Three lesions were missed by SDCT but detected by LVCT; 24 lesions were covered incompletely by SDCT, and 6 by LVCT. 21 lesions were detected completely by LVCT, but none by SDCT. CTP imaging of the brain using an increased detector width can detect additional ischaemic lesions and cover most ischaemic lesions completely.
PURPOSE To investigate Annexin V targeted molecular imaging of cardiomyocyte apoptosis in the ear... more PURPOSE To investigate Annexin V targeted molecular imaging of cardiomyocyte apoptosis in the early course after murine myocardial infarction. METHOD AND MATERIALS Myocardial infarction (MI) was induced in Kit+/+ mice by 30 minutes ligation of the left anterior descending artery (LAD) with subsequent reperfusion. Mice were injected with the Annexin V targeted molecular imaging probe Annexin-Vivo750 4 hours prior to imaging. Additionally mice were injected with a long-circulating iodine-based contrast agent (Exitron 12000) prior to imaging for better visualization of cardiac anatomy with subsequent facilitated organ segmentation. Hybrid FMT-XCT was performed 6 hours, 24 hours and 7 days after induction of ischemic injury. Molecular imaging signal for Annexin-Vivo750 was validated by ex-vivo immunohistochemistry and flow cytometry. RESULTS Successful image acquisition of both FMT and CT angiography was achieved in all mice. Molecular imaging signal for Annexin-Vivo750 could be localiz...
Uploads
Papers