Neural stem cell-mediated CE/CPT-11 enzyme/prodrug therapy in transgenic mouse model of intracerebellar medulloblastoma.

Medulloblastoma is a heterogeneous diffuse neoplasm that can be highly disseminated, and is the most common malignant childhood brain tumor. Although multimodal treatments have improved survival rates for patients with medulloblastoma, these tumors are associated with high morbidity and mortality. New treatment strategies are urgently needed to improve cure rates and, importantly, to spare normal brain tissue from neurotoxicity and patients from life-long cognitive and functional deficits associated with current therapies. In numerous preclinical brain tumor models, neural stem cells (NSCs) have shown great promise as delivery vehicles for therapeutic genes. Here, we have used an established, genetically modified human NSC line (HB1.F3.CD) to deliver carboxylesterase (CE) to cerebellar tumor foci and locally activate the prodrug camptothecin-11 (CPT-11) (Irinotecan) to the potent topoisomerase I inhibitor SN-38. HB1.F3.CD NSC tumor tropism, intratumoral distribution and therapeutic efficacy were investigated in clinically relevant experimental models. Magnetic resonance imaging was used for in vivo tracking of iron nanoparticle-labeled NSCs, and to assess the therapeutic efficacy of CE-expressing HB1.F3.CD cells. As compared with controls, a significant decrease in tumor growth rate was seen in mice that received both NSCs and CPT-11 as their treatment regimen. Thus, this study provides proof-of-concept for NSC-mediated CE/CPT-11 treatment of medulloblastoma, and serves as a foundation for further studies toward potential clinical application.

N staging of lung cancer patients with PET/MRI using a three-segment model attenuation correction algorithm: initial experience.

OBJECTIVES: Evaluate the performance of PET/MRI at tissue interfaces with different attenuation values for detecting lymph node (LN) metastases and for accurately measuring maximum standardised uptake values (SUVmax) in lung cancer patients. MATERIALS AND METHOD: Eleven patients underwent PET/CT and PET/MRI for staging, restaging or follow-up of suspected or known lung cancer. Four experienced readers determined the N stage of the patients for each imaging method in a randomised blinded way. Concerning metastases, SUVmax of FDG-avid LNs were measured in PET/CT and PET/MRI in all patients. A standard of reference was created with a fifth experienced independent reader in combination with a chart review. Results were analysed to determine interobserver agreement, SUVmax correlation between CT and MRI (three-segment model) attenuation correction and diagnostic performance of the two techniques. RESULTS: Overall interobserver agreement was high (κ = 0.86) for PET/CT and substantial (κ = 0.70) for PET/MRI. SUVmax showed strong positive correlation (Spearman's correlation coefficient = 0.93, P < 0.001) between the two techniques. Diagnostic performance of PET/MRI was slightly inferior to that of PET/CT, without statistical significance (P > 0.05). CONCLUSIONS: PET/MRI using three-segment model attenuation correction for LN staging in lung cancer shows a strong parallel to PET/CT in terms of SUVmax, interobserver agreement and diagnostic performance. KEY POINTS: •F18-FDG PET/MRI shows similar performance to F18-FDG PET/CT in lung cancer N staging. •PET/MRI has substantial interobserver agreement in N staging. •A three-segment model attenuation correction is reliable for assessing the mediastinum.

GARLA: Integrating Traditional and Modern Methodologies in Anatomy Education.

GARLA is an anatomy curriculum that combines dissection with applied anatomy. A two-week intensive dissection Boot-Camp is followed by a tripartite curriculum consisting of Gross Anatomy using a mixed reality headset, radiology, and physical exam/ultrasound skills. Student feedback has generally been positive.

Mixed Reality Anatomy Using Microsoft HoloLens and Cadaveric Dissection: A Comparative Effectiveness Study.

PURPOSE: As the amount of curricular material required of medical students increases, less time is available for anatomy; thus, methods to teach anatomy more efficiently and effectively are necessary. In this randomized controlled trial, we looked at the effectiveness of a mixed reality (MR) device to teach musculoskeletal anatomy to medical students compared with traditional cadaveric dissection. METHOD: Participating students were divided into three cohorts. Cohort 1 first studied upper limb anatomy in MR followed by lower limb anatomy through cadaveric dissection. Cohort 2 studied upper limb anatomy with cadaveric dissection followed by lower limb anatomy in MR. After the six sessions, a third cohort of 33 students who never received any teaching in MR was recruited to participate in the final practical exams as a control group. All 64 students completed two practical exams with equivalent content, one in the cadaver lab and one using MR. RESULTS: The average scores were 73.8% + 12.3 on the cadaver exam and 74.2% + 13.0 in MR. There is no statistical difference between these scores (p > 0.05). A correlation was found between the MR practical exam and cadaver practical exam scores (r = 0.74, p < 0.01) across all students. CONCLUSIONS: To our knowledge, this study marks the first time that MR was compared with traditional anatomy learning modalities in a multi-session, group course. Our results clearly indicate that medical students, regardless of the study modality, performed similarly on the MR and the cadaver practical exams.

[Characteristic imaging features of carcinoid tumors of the small bowel in MR enteroclysis]. / Morphologisches Erscheinungsbild neuroendokriner Tumoren des Dünndarms im MR-Enteroklysma.

PURPOSE: To determine the value of MR enteroclysis (MRE) in the localization and characterization of primary carcinoid tumors of the small bowel and to describe typical imaging features. MATERIAL AND METHODS: Twenty patients with suspicion of primary small bowel carcinoid tumors (pCT) were recruited to undergo MRE following nasojejunal intubation and small bowel filling with 2.5 l of 0.5% methylcellulose solution under MR fluoroscopic guidance. MRE was performed on a 1.5 T MR scanner including T2w SSFSE, SSFP and contrast enhanced T1w GRE sequences with fat saturation. Fifteen patients, who subsequently had surgery for resection of their pCT, were retrospectively included in the study. All MRE were analyzed as for the presence, location, number, size, multiplicity and morphologic appearance of the pCT by two board certified radiologists in consensus. The conspicuity of the tumors was rated for each sequence type separately, according to a 4-point rating scale. Signal intensity measurements were performed in tumor and muscle. The presence of desmoplastic reaction, vascular involvement and lymph node metastases was also analyzed. RESULTS: pCT were correctly identified and localized in 14/15 patients. Due to their hyperenhancement tumors was best detected on contrast-enhanced T1w fat saturated GRE sequences. SSFSE was clearly inferior with the tumors being either hyperintense or isointense to muscle. pCT appeared as nodular intraluminal masses in 40% of the cases, as focal wall thickening in 33.3% and in 20% with both. Mean size was 25 (7-46 mm) with a tendency to smaller size for ileal tumors. MRE failed to depict superficial micronodular peritoneal spread in one patient. Desmoplastic reaction was observed in 73.3% of the cases with mesenteric masses exhibiting lower signal than the pCT due to fibrotic changes. CONCLUSION: MRE is a valuable method for the detection and localization of primary carcinoid tumors, provided that appropriate bowel distension is achieved. Various characteristic morphologic features could be identified which may contribute to characterize pCT and their loco-regional metastases.

[Reduced bone density and bone pain :osteomalacia with hypophospatemia and hypophosphaturia]. / Erniedrigte Knochendichte und Knochenschmerzen : Osteomalazie mit Hypophosphatämie und Hyperphosphaturie.

Two patients aged 24 and 64 years presented at our hospital with similar symptoms including bone pain and muscle weakness. Basic laboratory tests and urinary diagnostics, bone densitometry and bone histology revealed severe osteomalacia with renal phosphate wasting. After the exclusion of other causes an extensive tumor search was performed due to suspected tumor-induced osteomalacia. In one patient a mesenchymal tumor was found in the thigh and completely resected. After surgery the patient showed a rapid recovery from osteomalacia. Because the search was unsuccessful in the other patient phosphorus supplementation in combination with calcitriol was started. Despite continuing renal phosphate wasting a significant increase in bone mineral density was observed.

NEW YOUNG STARS AND BROWN DWARFS IN THE UPPER SCORPIUS ASSOCIATION.

To improve the census of the Upper Sco association (~11 Myr, ~145 pc), we have identified candidate members using parallaxes, proper motions, and color-magnitude diagrams from several wide-field imaging surveys and have obtained optical and infrared spectra of several hundred candidates to measure their spectral types and assess their membership. We also have performed spectroscopy on a smaller sample of previously known or suspected members to refine their spectral types and evidence of membership. We have classified 530 targets as members of Upper Sco, 377 of which lack previous spectroscopy. Our new compilation of all known members of the association contains 1631 objects. Although the census of Upper Sco has expanded significantly over the last decade, there remain hundreds of candidates that lack spectroscopy. The precise parallaxes and proper motions from the second data release of Gaia should extend down to substellar masses in Upper Sco, which will greatly facilitate the identification of the undiscovered members.

Magnetic resonance enterography is feasible and reliable in multicenter clinical trials in patients with Crohn's disease, and may help select subjects with active inflammation.

BACKGROUND: Reliable tools for patient selection are critical for clinical drug trials. AIM: To evaluate a consensus-based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials. METHODS: This study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150-220 (n = 4); 220-450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14-day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES-CD). RESULTS: 37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test-retest and inter-reader reliability scores. The MaRIA scores for the terminal ileum had excellent test-retest and inter-reader reliability, with correlations >0.9. The proximal ileum showed strong within-reader agreement (0.90-0.96), and fair between-reader agreement (0.59-0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES-CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra-abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%. CONCLUSIONS: Magnetic resonance enterography of high-quality and reproducibility was feasible in a global multi- centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.

[Time needs in evaluating digital thoracic images on the monitor in comparison with alternator]. / Zeitbedarf bei der Befundung digitaler Thoraxaufnahmen am Monitor im Vergleich zum Alternator.

PURPOSE: Evaluation of time efficiency in softcopy reading versus hardcopy reading of digital chest x-rays. MATERIAL AND METHODS: 130 normal and pathologic chest x-rays in two plains were analyzed by 4 experienced radiologist at both a digital workstation and the light box. Reading time and switch time between two patient folders were measured as well as the frequency of post-processing at the monitor. RESULTS: Reading time at the workstation slightly exceeded reading time at the light box; differences were not statistically significant. Post-processing (frequency between 2% and 83%) did not significantly prolong reading time. Mean switch time between two patient folders was 4.3 sec at the workstation and 13.7 sec at the light box. CONCLUSION: As compared to hardcopy reading, softcopy reading of digital chest x-rays does not significantly increase reading time. Switch time between patient folders can be reduced at the workstation by a factor of two to four.

[Tumor-like lesion of the pancreas in chronic pancreatitis : imaging characteristics of computed tomography]. / Tumorähnliche Läsion des Pankreas bei chronischer Pankreatitis : Bildgebende Merkmale in der Computertomographie.

OBJECTIVE: The aim of this study was to describe the imaging findings for inflammatory pseudotumors in patients with chronic pancreatitis as detected in computed tomography (CT). MATERIALS AND METHODS: In this retrospective study 20 patients with chronic pancreatitis were included, who underwent an abdominal CT scan. In all patients the diagnosis was confirmed by surgery and histopathology. Imaging findings which have previously been described as typical for chronic pancreatitis and for inflammatory pseudotumors were assessed by two radiologists in consensus. Values of tissue density (HU) at CT were measured within the lesions and in the surrounding pancreatic tissue. RESULTS: In 90% of patients with histologically proven chronic pancreatitis, CT showed corresponding indicative findings. In 10 patients the resected specimen revealed an inflammatory pseudotumor, which was located in all cases within the pancreatic head. Using CT these 10 patients presented with calcifications within the lesion in 50% of the cases, an irregular dilatation of the main pancreatic duct in 90%, a "double duct sign" in 70%, an interrupted main pancreatic duct in the area of the lesion in 50%, a "duct penetrating sign" in 30%, an infiltration of adjacent structures in 10% and pathologically enlarged lymph nodes in 100% of the cases. In the venous contrasting phase six tumors were hypodense and four isodense compared to the surrounding pancreatic tissue. In six patients biphasic CT was performed and the mean difference in attenuation between inflammatory pseudotumors and surrounding parenchyma was significantly higher in the pancreatic phase than in the venous phase. DISCUSSION: Differentiation between inflammatory pseudotumors and adenocarcinoma remains difficult or even impossible. Typical signs indicative of an adenocarcinoma of the pancreatic head, such as dilatation of the common bile duct and/or the main pancreatic duct as well as enlarged lymph nodes, were also found in patients with inflammatory pseudotumors. Inflammatory pseudotumors showed low contrast between lesions and parenchyma in the venous phase and calcifications within the solid part of the tumor.

[Solid pseudopapillary pancreas tumors--often neglected]. / Solide pseudopapilläre Tumoren des Pankreas : Häufig vergessen.

Solid pseudopapillary tumors of the pancreas (SPTP) are rare tumors of the pancreas with low malignancy potential and a very good prognostic outcome after surgery. They typically occur in young women or adolescents and consist of solid, cystic and cystic-hemorrhagic components.Imaging findings in these tumors are characteristic and include a fibrotic capsule with a clear delineation and exhibit solid and cystic-hemorrhagic signal and density characteristics. Calcifications may be present in the periphery of the tumor. The tumor capsule shows contrast enhancement, the solid components in the periphery enhance in the early phase and gradually and inhomogeneously in late phases. MRI is superior to CT and other imaging modalities for characterization of SPTP. Awareness and knowledge of this tumor entity with an excellent prognosis is crucial to guide the patient towards effective, predominantly organ-sparing surgical treatment.

Quantitative and qualitative characterization of vascularization and hemodynamics in head and neck tumors with a 3D magnetic resonance time-resolved echo-shared angiographic technique (TREAT)--initial results.

The purpose of this paper is to characterize and quantify the vascularization and hemodynamic characteristics of head and neck tumors (HNT) with a dynamic 3D time-resolved echo-shared angiographic technique (TREAT) using the regular contrast agent (CA) bolus. Sixteen patients with HNT underwent 3D-TREAT during the CA administration on a 1.5-T magnetic resonance (MR) scanner. Using a parallel imaging acceleration factor of 2, 20 3D data sets at a temporal resolution of 2.3 s/frame were acquired. The quality of tumor delineation, vascularization type, and enhancement pattern were evaluated. Quantitative assessment included measurement of the contrast-to-noise ratio (CNR), determination of signal-intensity-over-time (SIT) curves, time-to-peak enhancement within the carotid arteries and the tumor, and the delay between both. TREAT was compared to conventional digital subtraction angiography (DSA) in six patients. Tumor delineation with TREAT was very good or good in 11/16 patients, and better with TREAT than with DSA in 3/6 cases. The CNR was significantly different for glomus tumors versus hypovascularized malignant tumors with TREAT (p=0.0001), but not on T1-weighted gradient echo (T1w GE) images. Qualitative assessment of tumor vascularization on dynamic TREAT shows good correlation (r=0.75) to quantitative SIT curves. We conclude that TREAT imaging permits the characterization of tumor vascularity and holds promise as a supplementary diagnostic tool in the differential diagnosis of HNT.

Functional renal imaging: nonvascular renal disease.

Functional renal imaging-a fast-growing field of MR-imaging-applies different sequence types to gather information about the kidneys other than morphology and angiography. This update article presents the current status of different functional imaging approaches and presents current and potential clinical applications. Apart from conventional in-phase and opposed-phase imaging, which already yields information about the tissue composition, BOLD (blood-oxygenation level dependent) sequences, DWI (diffusion-weighted imaging) sequences, perfusion measurements, and dedicated contrast agents are used.

[Cine MRI of the thorax in patients with pectus excavatum]. / CINE-MRT des Thorax bei Patienten mit Pectus excavatum.

BACKGROUND: Morphologic and dynamic assessment of respiratory chest kinetics was performed in patients with pectus excavatum deformity (PE) using dynamic MRI: cine MRI. MATERIAL AND METHODS: Seven consecutive patients with PE (aged 20.3 years+/-4.0) and ten healthy volunteers of comparable age underwent real-time cine MRI of the chest during breathing on a 1.5 T MR scanner (Magnetom Sonata, Siemens Medical Systems, Erlangen, Germany) using a standard phased array body coil and a half-Fourier single-shot turbo spin echo sequence (HASTE) for dynamic imaging. During deep inspiration and expiration, single-shot sequences were performed in one slice level over 20 s at a frequency of 1 image/s covering the entire thoracic cage in three orientations. Morphology and chest kinetics in patients with PE were analyzed and compared with normal values, and typical patterns of chest kinetics were noted. RESULTS: Three different types of chest morphology in PE were identified: (1) the generally flattened thoracic cage, (2) the "tilted" sternum, and (3) the focally deepened sternum. Three patterns of motion correspond to these morphological types: (1) elevation of the sternum and the anterior thoracic wall, (2) angulated elevation of the parasternal rib cage with persistent deepening of the sternum resembling a "wing beat" movement, and (3) increased diaphragmatic movements with limited chest wall dynamics. CONCLUSIONS: Cine MRI is an adequate radiation-free diagnostic modality for the dynamic imaging of both chest morphology and chest wall kinetics in patients with PE. The pectus severity index can easily be determined and three typical movement patterns of chest wall kinetics identified.

Internal fistulas in Crohn disease: magnetic resonance enteroclysis.

Internal fistulas (IFs) and abscesses are the most common complications of Crohn disease (CD). To reliably diagnose and clearly distinguish inflammatory or fibrostenotic manifestations of CD from its complications is of paramount importance to appropriately guide therapeutic decisions. Magnetic resonance enteroclysis (MRE), a recently introduced technique for small bowel imaging, has proved a high efficacy in the depiction of luminal and extraluminal manifestations of CD and holds great promise as a powerful diagnostic tool in the comprehensive diagnostic workup of this disease. As of yet, the characteristic imaging appearance of IFs on MRE has not been described in detail. This article reviews the performance of conventional imaging techniques and the current potential of MRE in the depiction of IFs in CD. Typical imaging morphology and characteristic imaging findings of IFs on MRE are described in detail and a newly defined and highly indicative imaging finding, the "star-sign," is presented and discussed.

[Comparison of 2D and 3D sequences for MRCP. Clinical value of the different techniques]. / Vergleich von 2D- und 3D-Sequenzen für die MRCP. Klinischer Stellenwert der einzelnen Techniken.

Magnetic resonance cholangio-pancreaticograpy (MRCP) is a non-invasive imaging modality of the pancreatico-biliary system which plays an increasingly important role in the clinical and diagnostic workup of patients with biliary or pancreatic diseases. The present review is designed to give an overview of the currently available and appropriate sequences, their technical background, as well as new developments and their relevance to the various clinical issues and challenges. The impact of the latest technical innovations, such as integrated parallel imaging techniques and navigator-based respiratory triggering, on the diagnostic capacities of MRCP is discussed. In this context, the individual value of RARE, T2w single shot turbo/fast spin echo (SSFSE) and the recently introduced 3D T2w turbo/fast spin echo sequences (T2w 3D-T/FSE) is reviewed. RARE imaging may be preferred in severely ill patients with limitations in cooperation, SSFSE is particularly effective in differentiating benign and malignant stenosis, and 3D-FSE offers additional advantages in the detection of small biliary concrements.

Interventional radiological procedures in impaired function of surgically implanted catheter-port systems.

PURPOSE: System-related complications in surgically implanted catheter-port systems (CPS) for intraarterial (i.a.) chemotherapy are well known. In most cases of complications, the treatment must be interrupted and the catheter-port system must be repaired surgically. We describe microinvasive interventional radiological procedures to correct some dysfunctions of CPS. METHODS: Five patients with repetitive dysfunction of CPS were treated with interventional techniques. Two patients presented with perfusion impairment, one patient had a pseudoaneurysm of the hepatic artery, and two patients presented with catheter displacement. Radiological interventions included mechanical recanalization with a guidewire, vascular stenting, and correction of catheter dislocation with a goose-neck snare. RESULTS: In all cases, correct function of the CPS was restored. No intervention-related complications occurred and surgery was avoided. Chemotherapy could be continued for a period of 4--10 months. CONCLUSION: For some system-related complications, minimally invasive radiological interventions can be used to restore the function of CPS for i.a. chemotherapy.

Liver intraarterial chemotherapy: use of the femoral artery for percutaneous implantation of catheter-port systems.

To provide intraarterial chemotherapy of the liver in 30 outpatients with colorectal cancer metastases and other malignancies, 32 catheter-port systems were implanted percutaneously via the femoral artery. Mean patency was 229 days. Percutaneous placement was feasible and safe. Compared with surgical placement, the overall complication rate (12%) was comparable or less.

[Percutaneous interventional radiologic implantation of intravenous port-catheter systems]. / Interventionell-radiologische perkutane Implantation intravenöser Port-Katheter-Systeme.

PURPOSE: Percutaneous interventional radiologic and surgical techniques of port-catheter implantation are described and compared with regard to the technical procedure and results. MATERIALS AND METHODS: In 53 patients with various malignancies interventional radiologic implantation of port-catheter systems into the subclavian vein was performed to provide long-term intravenous access for chemotherapy. The technical procedure, operation time, complication rates and long-term patency were compared with those of surgically implanted systems. RESULTS: Implantation was successful in all cases. Mean operation time was 36 min (range 20-55 min). Mean function time was 189 days (range 7-518). Primary patency rate was 92.5% with a total complication rate of 15% (8/53). In three patients (5.7%) pneumothorax was observed but did not require further treatment. In two cases (3.8%) local infection occurred, and in one patient (1.8%) a non-complicated wound dehiscence. In 12/53 patients (22.6%) the system was withdrawn. Among these, withdrawal was due to complications in 4/53 (7.6%) cases. CONCLUSIONS: Interventional radiologic implantation of long-term intravenous port-catheter systems is comparable to surgical placement with regard to both complication rate and long-term patency.