This prospective study compared a 1-d SPECT/CT protocol with the commonly used 3-d protocol for somatostatin receptor scintigraphy in patients with gastroenteropancreatic neuroendocrine neoplasms. Additionally, the influence of SPECT/CT on patient management was evaluated. Methods: From October 2011 to October 2012, all gastroenteropancreatic neuroendocrine neoplasm patients undergoing restaging with somatostatin receptor scintigraphy on a modern SPECT/CT device were enrolled in this study. The protocol consisted of planar imaging at 4, 24, and 48 h; low-dose SPECT/CT at 24 and 48 h; diagnostic CT at 24 h using a triple-phase delay after administration of contrast; and diagnostic SPECT/CT at 24 h. All components of the imaging data were reassessed by 3 masked interpreters. The results were compared with a reference standard based on all clinical, imaging, and histopathology follow-up data available (follow-up range, 24-36 mo; mean, 29.9 mo). The reference standard was defined by a study-specific interdisciplinary tumor board that also reassessed treatment decisions. Results; Thirty-one patients were eligible for analysis (18 men and 13 women; mean age, 60.4 y). Ten had no imaging signs of disease and remained disease-free during follow-up. Twenty-one had persistent or recurrent disease (82 lesions: 24 in the liver, 21 in the lymph nodes, 16 in bone, 12 in the pancreas, and 9 in other locations). The respective lesion detection rates for interpreters 1, 2, and 3 were 51.9%, 49.4%, and 71.6% for low-dose SPECT/CT at 24 h; 51.9%, 55.6%, and 67.9% for low-dose SPECT/CT at 48 h; 63.0%, 70.4%, and 85.2% for diagnostic CT; and 77.8%, 84.0%, and 88.9% for diagnostic SPECT/CT. Interobserver agreement was moderate for diagnostic SPECT/CT (K = 0.44), diagnostic CT (K = 0.43), low-dose SPECT/CT at 48 h (K = 0.61), and low-dose SPECT/CT at 24 h (K = 0.55). For planar imaging, interobserver agreement was fair after 48 h (K = 0.36) and 24 h (K = 0.38) and moderate after 4 h (K = 0.42). Every lesion detectable on planar imaging or low dose SPECT/CT was also detectable on diagnostic SPECT/CT. The CT and SPECT components of diagnostic SPECT/CT strongly complemented each other, as 34 of 82 lesions (41.4%) were detected on only the CT component or only the SPECT component. Therapeutic management was influenced by the diagnostic SPECT/CT interpretation in 8 of 31 patients (25.8%). Conclusion: The highest detection rates were achieved by diagnostic SPECT/CT. Thus, a more patient-friendly 1-d protocol is feasible. Furthermore, multiphase SPECT/CT affected management in about a quarter of patients.

Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients.

Evaluierung der Schwellenwert-basierten Lebervolumetrie mittels Gd-EOB-DTPA-verstärkter MRT inklusive einer modulierten 3D-Sequenz.

Retrospektive Evaluierung morphologischer Charakteristika und Kontrastmittel-Verhalten der GD-EOB-verstärkten MRT im Vergleich zur histopathologischen Bordeaux Subgruppenklassifikation von hepatozellulären Adenomen (HCA).

Retrospektive Analyse der MRT-Charakteristika mit hepatozytenspezifischem Kontrastmittel (Gd-EOB) von histologisch gesicherten Leberzelladenomen (LZA's) und fokal nodulären Hyperplasien (FNH's) sowie Durchführung einer systematischen Literaturrecherche

Objectives To estimate the additional value of an increased flip angle of 35° in late phase Gd-EOB-DTPA-enhanced magnetic resonance cholangiography, as compared to T2w-MRCP. Methods 40 adult patients underwent Gd-EOB-DTPA enhanced MRI of the liver including a T2-weighted 3D TSE MRCP (T2w-MRCP) as well as a late phase T1-weighted THRIVE sequences applying a flip angle of 35° (fa35). Two experienced observers evaluated the images regarding the delineation of the different biliary regions using a three-point grading system. A five-point scale was applied to determine the readers’ confidence in identifying anatomical variations of the biliary tree. ROI analysis was performed to compare the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. Results The quality for visualizing the biliary tree differed between T2w-MRCP and fa35 (p = <0.001). Late phase EOB-MRC was rated as good for delineating the entire biliary system, whereas T2w-MRCP received an overall poor rating. Especially the depiction of the intrahepatic bile ducts was estimated as problematic in T2w-MRCP. T2w-MRCP and fa35 revealed a discordant assessment of anatomical variations in 12.5% of the cases, comprising a generally higher confidence level for fa35 (4.0 ± 1.1 vs. 2.2 ± 1.2, p = <0.001). SNR proofed to be significantly higher in fa35 (p = <0.001), whereas T2w-MRCP revealed a significantly higher CNR (<0.001). Conclusions Gd-EOB-DTPA enhanced magnetic resonance cholangiography acquired with a flip angle of 35° revealed a better diagnostic performance compared to T2w-MRCP and might be a valuable adjunct in assessing functional bile duct abnormalities.

Der klinische Einsatz des Enzyms Arginine Deiminase (ADI) zeigt vielversprechende Ergebnisse in Patienten mit metastasiertem malignen Melanom. ADI entzieht den Zellen die Aminosäure L-Arginine (Arg), welche eine Vielzahl an Tumorentitäten nicht selbstständig synthetisieren können (Auxotrophie). Die Folge ist der apoptotische Zelltod. In unserer Studie haben wir versucht mittels 18F-FDG PET, 18F-FLT PET und AngioSense750 FMT ein Therapiemonitoring zu etablieren bzw. in respondern das Therapieansprechen vorherzusagen.

BACKGROUND:The optimal sequence for Gd-EOB-DTPA uptake measurement in the liver with the purpose of liver function measurement is still not defined.PURPOSE:To prospectively evaluate the effect of an increased flip angle (FA) of a T1-weighted fat-saturated 3D sequence for the measurement of hepatocyte uptake of Gd-EOB-DTPA magnetic resonance imaging (MRI) after right portal vein embolization (PVE).MATERIAL AND METHODS:Ten patients who received a PVE prior to an extended hemihepatectomy were examined 14 days after PVE using Gd-EOB-DTPA enhanced MRI of the liver using the standard FA of 10° and the increased FA of 30°.RESULTS:Relative enhancement of the right liver lobe (RLL) was 0.52 ± 0.12 for 10° and 1.41 ± 0.39 for 30°. Relative enhancement of the left liver lobe (LLL) was 0.58 ± 0.11 for 10° and 2.05 ± 0.61 for 30°. Relative enhancement of the RLL was significantly higher for 30° than for 10° (P = 0.009) and significantly higher in the 30° than in the 10° sequences (P = 0.005) for the LLL.CONCLUSION:A flip angle of 30° increases the contrast between liver partitions with and without portal venous embolization. Thereby, the sensitivity for differences in uptake intensity is increased. This could be of value for a more exact determination of differences in regional liver function and, consequently, the estimation of the future remnant liver function.

Background Despite novel software solutions, liver volume segmentation is still a time-consuming procedure and often requires further manual optimization. With the high signal intensity of the liver parenchyma in Gd-EOB enhanced magnetic resonance imaging (MRI), liver volume segmentation may be improved. Purpose To evaluate the practicability of threshold-based segmentation of the liver volume using Gd-EOB-enhanced MRI including a customized three-dimensional (3D) sequence. Material and Methods A total of 20 patients examined with Gd-EOB MRI (hepatobiliary phase T1-weighted (T1W) 3D sequence [VIBE]; flip angle [FA], 10° and 30°) were enrolled in this retrospective study. The datasets were independently processed by two blinded observers (O1 and O2) in two ways: manual (man) and threshold-based (thresh; study method) segmentation of the liver each followed by an optimization step (man+opt and thresh+opt; man+opt [FA10°] served as reference method). Resulting liver volumes and segmentation times were compared. A liver conversion factor was calculated in percent, describing the non-hepatocellular fraction of the total liver volume, i.e. bile ducts and vessels. Results Thresh+opt (FA10°) was significantly faster compared to the reference method leading to a median volume overestimation of 4%/8% (P < 0.001). Using thresh+opt (FA30°), segmentation was even faster (P < 0.001) and even reduced median volume deviation of 0%/2% (O1/O2; both P > 0.2). The liver conversion factor was found to be 10%. Conclusion Threshold-based liver segmentation employing Gd-EOB-enhanced hepatobiliary phase standard T1W 3D sequence is accurate and time-saving. The performance of this approach can be further improved by increasing the FA.

Evaluation of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiation of pancreatic intraductal papillary mucinous neoplasm (IPMN) subtypes based on objective imaging criteria.

Objective: To evaluate postinterventional magnetic resonance imaging (MRI) characteristics following MRI-guided laser ablation of osteoid osteoma (OO).Materials and methods: 35 patients treated with MRI-guided laser ablation underwent follow-up MRI immediately after the procedure, after 3, 6, 12, 24, 36, and up to 48 months. The imaging protocol included multiplanar fat-saturated T2w TSE, unenhanced and contrast-enhanced T1w SE, and subtraction images. MR images were reviewed regarding the appearance and size of treated areas, and presence of periablation bone and soft tissue changes. Imaging was correlated with clinical status.Results: Mean follow-up time was 13.6 months. 28/35 patients (80%) showed a postinterventional "target-sign" appearance consisting of a fibrovascular rim zone and a necrotic core area. After an initial increase in total lesion diameter after 3 months, a subsequent progressive inward remodeling process of the zonal compartments was observed for up to 24 months. Periablation bone and soft tissue changes showed a constant decrease over time. MR findings correlated well with the clinical status. Clinical success was achieved in 32/35 (91%).Conclusions: Evaluation of long-term follow-up MRI after laser ablation of OO identified typical postinterventional changes and thus may contribute to the interpretation of therapeutic success and residual or recurrent OO in suspected cases. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE:The objective of this study was to evaluate computed tomography (CT) findings in patients with sepsis with unknown inflammatory focus and acute respiratory distress syndrome.METHODS:Acute respiratory distress syndrome findings on CT of 36 patients with sepsis were graded on a 6-point scale, and the percentage of affected lung was estimated. Resulting CT scores were correlated to intensive care scores and survival.RESULTS:Forty-four percent of the patients died, revealing a significantly higher CT score than survivors (P = 0.01). Survivors showed larger areas of unaffected lung (P < 0.001), whereas patients with fatal outcome had more ground-glass opacities (P = 0.002; sensitivity, 73%; specificity, 57%) and traction bronchiectasis (P = 0.009; sensitivity, 54%; specificity, 68%). Pulmonary findings on CT did not allow discriminating between a pulmonary and extrapulmonary focus. No significant coherence between CT score and intensive care scores could be revealed.CONCLUSIONS:A CT scoring system based on pulmonary findings in patients with sepsis with acute respiratory distress syndrome comprises prognostic implications in terms of the patients' survival.

OBJECTIVES:The objective of this study was to evaluate the accuracy, safety, and efficacy of magnetic resonance (MR)-guided periradicular nerve root injection therapy using an open 1.0-T magnetic resonance imaging (MRI) system with fast dynamic imaging. MATERIALS AND METHODS:Between April 2008 and November 2011, a total of 249 MR-guided periradicular nerve root injections were performed in 141 patients experiencing lumbosacral radicular pain. All interventions were performed in an open 1.0-T MRI system. An interactive proton-density-weighted fast spin-echo sequence was used for real-time guidance. An in-room monitor, a wireless MR mouse for operator-controlled multiplanar imaging, a flexible surface coil, and an MR-compatible 20-G needle were used. Informed consent was obtained from all patients. Clinical outcome was evaluated through clinical follow-up and a questionnaire before injection therapy (baseline) and 6 months after using a numeric visual analog scale. RESULTS:All procedures were technically successful. No major complications occurred. At 6 months, of the 103 patients (197 injections; 57 men, 46 women; mean age, 49.5 years; range, 20-80) who enrolled in the outcome analysis, 14.6% reported complete remission of radicular pain; 53.4%, significant relief of pain; 22.3%, mild relief; and 9.7%, no relief of pain. We found a significant decrease of the visual analog scale score from the preintervention compared with the follow-up after 6 months (P < 0.001). No significant difference in the outcome was observed between the patients with degenerative foraminal stenoses and the patients with herniated disks. CONCLUSIONS:Magnetic resonance fluoroscopy-guided periradicular injection therapy for the lumbosacral spine under open 1.0-T MRI guidance is accurate, safe, and efficient in the symptomatic treatment of radicular pain. This technique may be a promising alternative to fluoroscopy- or computed tomography-guided spinal injections in the lumbosacral region, especially for young patients and patients undergoing serial therapeutic regimens.

Ziele: Evaluation des technischen Erfolgs, der Effektivität und Sicherheit der MR-gesteuerten Infiltrationstherapie lumbosakraler Spinalwurzeln im offenen 1.0 T MRT. Methode: Zwischen April 2008 und November 2011 wurden 249 MR-gesteuerte periradikuläre Infiltrationen in 141 Patienten mit lumbosakraler Radikulopathie durchgeführt. Alle Interventionen erfolgten im offenen 1.0 T MRT. Zur Echtzeit-Bildsteuerung wurde eine interaktive T1w TSE Sequenz genutzt. Es wurden eine MR-kompatible 20-G Nadel, eine flexible Oberflächenspule, ein „in-room“ Monitor und eine „Bluetooth“ Funkmaus für die multiplanare Bildsteuerung im MR Scanner verwendet. Der klinische Erfolg wurde anhand der visuellen Analogskala (VAS) vor Infiltrationstherapie (“baseline“) und bis zu 6 Monaten erhoben. Ergebnis: Alle Infiltrationen waren technisch erfolgreich, ohne Auftreten von Komplikationen. Von 103 in die statistische Auswertung eingeschlossenen Patienten (57 m, 46 w; mittl. Alter, 49.5J; 20 – 80J) zeigten nach 6 Monaten 14.6% eine komplette Remission der Radikulopathie, 53.4% eine signifikante, 22.3% eine milde und 9.7% der Patienten keine Schmerzbesserung. Es zeigte sich eine signifikante Abnahme des VAS-scores pre-interventionell verglichen mit dem 6-Monats follow-up (p<.001). Es wurde kein signifikanter Unterschied im outcome zwischen Patienten mit degenerativer Foraminalstenose und Patienten mit Diskusprolaps gefunden. Schlussfolgerung: Die MR-gesteuerte lumbosakrale Infiltrationstherapie im offenen 1.0 T MRT ist präzise, sicher und effektiv in der symptomatischen Behandlung der Radikulopathie. Diese Therapieoption stellt eine vielversprechende Alternative zur Fluoroskopie- oder CT-gesteuerten spinalen Infiltration dar, insbesondere bei jungen Patienten und Patienten mit seriellem Therapieschema.

Purpose Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option. Procedures The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo . Results All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines. Conclusion We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.

Cellular therapies require methods for noninvasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate a strong contrast in magnetic resonance imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However, MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles (sMPIOs) with a functionalizable particle surface. Particles with magnetite content of >40% were composed using the sol-gel process. The particle surfaces were covered with COOH groups. Fluorescein, poly-l-lysine (PLL), and streptavidin (SA) were covalently attached. Monodisperse sMPIOs had an average size of 1.18 μm and an iron content of about 1.0 pg Fe/particle. Particle uptake, toxicity, and imaging studies were performed using HuH7 cells and human and rat hepatocytes. sMPIOs enabled rapid cellular labeling within 4 h of incubation; PLL-modified particles had the highest uptake. In T2*-weighted 3.0 T MRI, the detection threshold in agarose was 1,000 labeled cells, whereas in T1-weighted LAVA sequences, at least 10,000 cells were necessary to induce sufficient contrast. Labeling was stable and had no adverse effects on labeled cells. Silica is a biocompatible material that has been approved for clinical use. sMPIOs could therefore be suitable for future clinical applications in cellular MRI, especially in settings that require strong cellular contrast. Moreover, the particle surface provides the opportunity to create multifunctional particles for targeted delivery and diagnostics.

Based on their inability to express argininosuccinate synthetase (ASS), some cancer entities feature the characteristic of L-arginine (Arg) auxotrophy. This inability to intrinsically generate Arg makes them applicable for arginine deiminase (ADI) treatment, an Arg-depleting drug. Arg is also used for the synthesis of endothelial nitric oxide (NO), which mainly confers vasodilatation but is also considered to have a major influence on tumor vascularization. The purpose of this study was to define changes in tumor vasculature in an ADI-treated melanoma xenograft mouse model using the blood pool agent AngioSense 750 and fluorescence molecular tomography (FMT). We used an ASS-negative melanoma xenograft mouse model and subjected it to weekly ADI treatment. Changes in tumor size were measured, and alterations in tumor vasculature were depicted by FMT and CD31 immunohistochemistry (IHC). On ADI treatment and effective antitumor therapy, we observed a drop in NO plasma levels and visualized changes in tumor vascularization with FMT and IHC. ADI treatment in melanoma xenografts has a tumor-reducing effect, which can be noninvasively imaged by quantifying tumor vascularization with FMT and IHC.

Liver cell transplantation: conceptual background, current clinical situation & the need for noninvasive monitoring Liver cell transplantation (LCT) is an evolving therapeutic approach for the treatment of a variety of liver diseases and is a potential future alternative to solid liver transplantation [1]. LCT is based on the administration of liver cells in suspension, which implies several conceptual advantages over whole-organ transplantation. Cells are isolated from donor livers or liver lobes that were rejected or unused for whole-organ transplantation, and this expands the donor pool for liver grafts and allows for the treatment of multiple patients with cells from one donor organ. Liver cells can be cryopreserved prior to transplantation, which enables the pooling of cells and on-demand or scheduled applications. Cells can be infused either into the liver or to an ectopic implantation site, such as the spleen or the peritoneal cavity, by interventional procedures. This method is also less invasive than whole-organ transplantation and offers the chance to treat critically ill or very young patients who are not suitable for whole-organ transplantation. The cells can engraft in the recipient liver or at the ectopic implantation site and provide metabolic activity without the need for removing the diseased liver. Thus, the native liver can be left in place and may have a chance of recovery [2–4]. Following extensive animal studies, LCT has been clinically evaluated for the major indications of liver transplantation (Table 1) [4–34]. Unfortunately, LCT has not yet achieved sustainable benefits for patients with acute liver failure and chronic liver disease [1]. However, LCT has evolved as an effective bridging strategy for patients suffering from inborn metabolic liver disorders. In cases with a single deficient enzyme, such as urea cycle defects [16–21] or glycogen storage disease [12,13], donor hepatocytes can substitute the missing function without the need for replacing the whole organ. Approximately 35 children and adults who received LCT for liver-based metabolic disease have been reported in the literature to date. The majority of these studies were conducted within the last few years [35]. Liver cell administration proved to be feasible and safe, and the majority of the cases demonstrated temporal clinical improvements, such as bilirubin or urea reduction [20] or the presence of soluble factors synthesized by transplanted cells [19]. However, in almost all cases, patients needed to undergo liver transplantation a few months after LCT due to recurrence of symptoms and further aggravation of the disease. There are still many open questions and barriers for the successful treatment of liver disease by LCT [36]. One of the persisting problems is the lack of evidence for the longterm engraftment and function of transplanted cells. Possible reasons for the unsustainable longterm outcome of LCT include insufficient cell translocation through the endothelial cell barrier [37], insufficient cell engraftment into the liver Liver cell transplantation was developed as a therapeutic alternative to solid liver transplantation in the management of liver-based metabolic disorders and may be useful for the treatment of acute or chronic liver failure. While clinical studies have demonstrated temporal amelioration of the symptoms of metabolic liver disorders by transplanted liver cells, the long-term outcome of liver cell transplantation is still insufficient. A major limitation for improving liver cell transplantation is the inability to track the fate of cells once they have been infused. Radionuclide-based imaging, MRI and optical methods have been investigated as methods for noninvasive monitoring of liver cell transplantation. This article summarizes and critically discusses these approaches, with a special focus on MRI-based tracking of transplanted liver cells and provides an outlook on possible clinical applications for the near future.