TY - JOUR A1 - Lapa, Constantin A1 - Schreder, Martin A1 - Schirbel, Andreas A1 - Samnick, Samuel A1 - Kortüm, Klaus Martin A1 - Herrmann, Ken A1 - Kropf, Saskia A1 - Einsele, Herrmann A1 - Buck, Andreas K. A1 - Wester, Hans-Jürgen A1 - Knop, Stefan A1 - Lückerath, Katharina T1 - [\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values JF - Theranostics N2 - Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018). [\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma. KW - medicine KW - multiple myeloma KW - FDG KW - molecular imaging KW - CXCR4 KW - PET KW - radionuclide therapy KW - theranostics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172106 VL - 7 IS - 1 ER - TY - INPR A1 - Werner, Rudolf A. A1 - Andree, Christian A1 - Javadi, Mehrbod S. A1 - Lapa, Constantin A1 - Buck, Andreas K. A1 - Higuchi, Takahiro A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Rowe, Steven P. A1 - Pienta, Kenneth J. T1 - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging T2 - Urology - The Gold Journal N2 - No abstract available. KW - 18F-DCFPyL KW - Virchow Node KW - PSMA-PET KW - Virchow Node KW - Positron Emission Tomography KW - Prostate Cancer KW - PET Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161103 SN - 0090-4295 N1 - This is the accepted manuscript of Rudolf Werner, Christian Andree, Mehrbod S. Javadi, Constantin Lapa, Andreas K. Buck, Takahiro Higuchi, Martin G. Pomper, Michael A.Gorin, Steven P.Rowe, Kenneth J. Pienta: A Voice From the Past: Re-Discovering the Virchow Node with PSMA-Targeted 18F-DCFPyL PET Imaging. Published in Urology 117(2018), p. 18-21. https://doi.org/10.1016/j.urology.2018.03.030 N1 - Die finale Version dieses Artikels steht unter https://doi.org/10.1016/j.urology.2018.03.030 oder https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-164632 open access zur Verfügung. ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Andree, Christian A1 - Javadi, Mehrbod S. A1 - Lapa, Constantin A1 - Buck, Andreas K. A1 - Higuchi, Takahiro A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Rowe, Steven P. A1 - Pienta, Kenneth J. T1 - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging JF - Urology - The Gold Journal N2 - No abstract available. KW - 18F-DCFPyL KW - PET KW - PSMA-PET KW - Positron Emission Tomography KW - Prostate Cancer KW - Virchow Node Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164632 SN - 0090-4295 VL - 117 ER - TY - JOUR A1 - Kosmala, Aleksander A1 - Serfling, Sebastian E. A1 - Dreher, Niklas A1 - Lindner, Thomas A1 - Schirbel, Andreas A1 - Lapa, Constantin A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Weich, Alexander A1 - Werner, Rudolf A. T1 - Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography JF - Cancers N2 - (1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs. KW - PET KW - [\(^{68}\)Ga]Ga-FAPI KW - theranostics KW - radioligand therapy KW - fibroblast activation protein Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275154 SN - 2072-6694 VL - 14 IS - 11 ER - TY - CHAP A1 - Werner, Rudolf A1 - Hayakawa, Nobuyuki A1 - Arias-Loza, Paula-Anah A1 - Wakabayashi, Hiroshi A1 - Shinaji, Tetsuya A1 - Lapa, Constantin A1 - Pelzer, Theo A1 - Higuchi, Takahiro T1 - Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell T2 - Nuklearmedizin N2 - Einleitung: Die linksventrikuläre diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann. Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG über die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikuläre Ejektionsfraktion (EF) und die Peak Füllrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Größe des Rattenherzes angepasst wurde. Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, bestätigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.). Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der frühen diabetischen Kardiomyopathie nachgewiesen werden. KW - Positronen-Emissions-Tomografie KW - Diabetes KW - diabetische Kardiomyopathie KW - Positronen-Emissions-Tomografie KW - PET KW - EKG KW - ECG KW - ECG-gated Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161396 UR - http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php SN - 0029-5566 N1 - This article is not an exact copy of the original published article in Nuklearmedizin. The definitive publisher-authenticated version of „Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell. Nuklearmedizin 2017; 56 (Abstract Nr.: V119).“ is available online at http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php VL - 56 IS - 2 PB - Schattauer Verlag ER - TY - JOUR A1 - Israel, Ina A1 - Ohsiek, Andrea A1 - Al-Momani, Ehab A1 - Albert-Weissenberger, Christiane A1 - Stetter, Christian A1 - Mencl, Stine A1 - Buck, Andreas K. A1 - Kleinschnitz, Christoph A1 - Samnick, Samuel A1 - Sirén, Anna-Leena T1 - Combined [\(^{18}\)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice JF - Journal of Neuroinflammation N2 - Background Traumatic brain injury (TBI) is a major cause of death and disability. Neuroinflammation contributes to acute damage after TBI and modulates long-term evolution of degenerative and regenerative responses to injury. The aim of the present study was to evaluate the relationship of microglia activation to trauma severity, brain energy metabolism, and cellular reactions to injury in a mouse closed head injury model using combined in vivo PET imaging, ex vivo autoradiography, and immunohistochemistry. Methods A weight-drop closed head injury model was used to produce a mixed diffuse and focal TBI or a purely diffuse mild TBI (mTBI) in C57BL6 mice. Lesion severity was determined by evaluating histological damage and functional outcome using a standardized neuroscore (NSS), gliosis, and axonal injury by immunohistochemistry. Repeated intra-individual in vivo μPET imaging with the specific 18-kDa translocator protein (TSPO) radioligand [\(^{18}\)F]DPA-714 was performed on day 1, 7, and 16 and [\(^{18}\)F]FDG-μPET imaging for energy metabolism on days 2–5 after trauma using freshly synthesized radiotracers. Immediately after [\(^{18}\)F]DPA-714-μPET imaging on days 7 and 16, cellular identity of the [\(^{18}\)F]DPA-714 uptake was confirmed by exposing freshly cut cryosections to film autoradiography and successive immunostaining with antibodies against the microglia/macrophage marker IBA-1. Results Functional outcome correlated with focal brain lesions, gliosis, and axonal injury. [\(^{18}\)F]DPA-714-μPET showed increased radiotracer uptake in focal brain lesions on days 7 and 16 after TBI and correlated with reduced cerebral [\(^{18}\)F]FDG uptake on days 2–5, with functional outcome and number of IBA-1 positive cells on day 7. In autoradiography, [\(^{18}\)F]DPA-714 uptake co-localized with areas of IBA1-positive staining and correlated strongly with both NSS and the number of IBA1-positive cells, gliosis, and axonal injury. After mTBI, numbers of IBA-1 positive cells with microglial morphology increased in both brain hemispheres; however, uptake of [\(^{18}\)F]DPA-714 was not increased in autoradiography or in μPET imaging. Conclusions [\(^{18}\)F]DPA-714 uptake in μPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed head TBI. KW - neuroinflammation KW - TBI KW - immunohistochemistry KW - weight drop KW - PET KW - diffuse KW - focal KW - TSPO KW - autoradiography KW - IBA-1 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146606 VL - 13 IS - 140 ER - TY - JOUR A1 - Lapa, Constantin A1 - Herrmann, Ken A1 - Schirbel, Andreas A1 - Hänscheid, Heribert A1 - Lückerath, Katharina A1 - Schottelius, Margret A1 - Kircher, Malte A1 - Werner, Rudolf A. A1 - Schreder, Martin A1 - Samnick, Samuel A1 - Kropf, Saskia A1 - Knop, Stefan A1 - Buck, Andreas K. A1 - Einsele, Hermann A1 - Wester, Hans-Juergen A1 - Kortüm, K. Martin T1 - CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma JF - Theranostics N2 - C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted. KW - medicine KW - multiple myeloma KW - PET KW - CXCR4 KW - theranostics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172095 VL - 7 IS - 6 ER - TY - JOUR A1 - Schadt, Fabian A1 - Israel, Ina A1 - Samnick, Samuel T1 - Development and Validation of a Semi-Automated, Preclinical, MRI-Template Based PET Image Data Analysis Tool for Rodents JF - Frontiers in Neuroinformatics N2 - AimIn PET imaging, the different types of radiotracers and accumulations, as well as the diversity of disease patterns, make the analysis of molecular imaging data acquired in vivo challenging. Here, we evaluate and validate a semi-automated MRI template-based data analysis tool that allows preclinical PET images to be aligned to a self-created PET template. Based on the user-defined volume-of-interest (VOI), image data can then be evaluated using three different semi-quantitative parameters: normalized activity, standardized uptake value, and uptake ratio. Materials and MethodsThe nuclear medicine Data Processing Analysis tool (NU_DPA) was implemented in Matlab. Testing and validation of the tool was performed using two types of radiotracers in different kinds of stroke-related brain diseases in rat models. The radiotracers used are 2-[\(^{18}\)F]fluoro-2-deoxyglucose ([\(^{18}\)F]FDG), a metabol\(^{68}\)Ga]Ga-Fucoidan, a target-selective radioligand specifically binding to p-selectin. After manual image import, the NU_DPA tool automatically creates an averaged PET template out of the acquired PET images, to which all PET images are then aligned onto. The added MRI template-based information, resized to the lower PET resolution, defines the VOI and also allows a precise subdivision of the VOI into individual sub-regions. The aligned PET images can then be evaluated semi-quantitatively for all regions defined in the MRI atlas. In addition, a statistical analysis and evaluation of the semi-quantitative parameters can then be performed in the NU_DPA tool. ResultsUsing ischemic stroke data in Wistar rats as an example, the statistical analysis of the tool should be demonstrated. In this [\(^{18}\)F]FDG-PET experiment, three different experimental states were compared: healthy control state, ischemic stroke without electrical stimulation, ischemic stroke with electrical stimulation. Thereby, statistical data evaluation using the NU_DPA tool showed that the glucose metabolism in a photothrombotic lesion can be influenced by electrical stimulation. ConclusionOur NU_DPA tool allows a very flexible data evaluation of small animal PET data in vivo including statistical data evaluation. Using the radiotracers [\(^{18}\)F]FDG and [\(^{68}\)Ga]Ga-Fucoidan, it was shown that the semi-automatic MRI-template based data analysis of the NU_DPA tool is potentially suitable for both metabolic radiotracers as well as target-selective radiotracers. KW - data analysis KW - Matlab KW - MRI KW - PET KW - positron emission tomography KW - preclinical imaging Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240289 SN - 1662-5196 VL - 15 ER - TY - THES A1 - Omert, Leilah Marie-Luise T1 - Einfluss systemischer Therapie auf die funktionelle Bildgebung des Multiplen Myeloms T1 - Influence of systemic therapy on functional imaging of Multiple Myeloma N2 - Das Multiple Myelom (MM) ist eine maligne hämatologische Erkrankung, die trotz großer Fortschritte in der Therapie immer noch eine schlechte Prognose hat. Bisher ist es nicht möglich, mit einem bildgebenden Verfahren alle Fragen der Diagnostik, der Stadieneinteilung, des Therapiemonitorings und der Evaluation der Prognose des Multiplen Myeloms zu klären. Da es sich beim Multiplen Myelom aber um eine stark heterogene Erkrankung handelt, die eine frühzeitige individuelle Therapie erfordert, ist es unbedingt nötig Verfahren zu entwickeln, die eine spezifische Charakterisierung der Erkrankung bei jedem einzelnen Patienten ermöglichen. In der vorliegenden Arbeit wurden die MM-Zelllinien INA-6, MM.1S und OPM-2 mit dem Proteasominhibitor MLN9708 behandelt. Behandelte und unbehandelte Zellen wurden mit dem Standardtracer 2-[18F]-Fluoro-2-Desoxy-D-Glukose (18F-FDG) oder dem in der Anwendung beim Multiplen Myelom neuen Aminosäuretracer [11C]-Methionin (11C-MET) inkubiert und die Aufnahme der Tracer zu bestimmten Zeitpunkten gemessen. Des Weiteren wurde die Ausprägung biologischer Merkmale der MM-Pathogenese bei behandelten und unbehandelten Zellen untersucht. Anschließend wurde ermittelt, ob ein Zusammenhang zwischen der Höhe der Traceraufnahme und der Ausprägung biologischer Merkmale der MM-Pathogenese bei behandelten und unbehandelten Zellen besteht. Hierdurch soll geklärt werden, ob 11C-MET besser zur Diagnostik, dem Therapiemonitoring und der Evaluation der Prognose des Multiplen Myeloms geeignet ist als der Standardtracer 18F-FDG. Es zeigte sich eine signifikant höhere 11C-MET-Aufnahme sowohl unbehandelter als auch behandelter Zellen im Vergleich zu 18F-FDG. Außerdem war eine Unterscheidung zwischen behandelten und unbehandelten Zellen mit 11C-MET besser möglich als mit 18F-FDG. Zwischen Traceraufnahme und biologischen Merkmalen der MM-Pathogenese, wie Proliferation, Expression von intrazellulären Leichtketten, CXCR4 und CD138, ergaben sich für behandelte und unbehandelte Zellen variable Zusammenhänge. Die Ergebnisse legen nahe, dass 11C-MET besser zur Diagnostik und zum Therapiemonitoring des Multiplen Myeloms geeignet ist als der Standardtracer 18F-FDG. Ob 11C-MET auch zur Stadieneinteilung und zur Evaluation der Prognose des Multiplen Myeloms besser geeignet ist als 18F-FDG, muss in weiteren Studien untersucht werden. N2 - Despite new therapies Multiple Myeloma (MM) remains a hematologic malignancy with poor prognosis. Because of marked disease heterogeneity outcomes are extremely variable. The role of functional imaging, such as positron emission tomography for diagnosis, therapy monitoring, staging and prognostication is being investigated for a few years. This study evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG (glucose-utilization) for diagnosis, therapy monitoring, staging and outcome prediction of MM. Influence of proteasome-inhibitor MLN9708 (Ixazomib) on radiotracer-uptake of different MM cell-lines was analyzed and related to tumor-biology. Both untreated and treated MM cells significantly took up more 11C-Methionine than 18F-FDG. Discrimination of treated and untreated cells was only possible with 11C-Methionine. Correlations between tracer uptake and tumor biology were variable for both tracers. These results suggest that 11C-Methionine is superior to 18F-FDG in diagnosis and therapy monitoring of MM. The suitability of 11C-Methionine for staging and prognostication has to be evaluated in further studies. KW - Multiples Myelom KW - Bildgebung KW - PET Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154793 ER - TY - THES A1 - Becker, Kilian T1 - Entwicklung eines 3D-Ganzkörper-Ultraschalls an Kleintieren für morphologische Bildgebung, Volumetrie und Bildfusion mit PET T1 - Development of a 3D whole-body ultrasound in small animals for morphological imaging, volumetry and image fusion with PET N2 - Einleitung: Ultraschall wird seit mehr als 50 Jahren in der Medizin eingesetzt und ist mittlerweile ein unverzichtbares diagnostisches Verfahren, es erlaubt eine nicht-invasive Darstellung der Morphologie und Funktion von Organen in Echtzeit. In der Kleintierbildgebung dominieren bisher zur morphologischen Bildgebung Computertomographie (CT) und Magnetresonanztomographie (MRT). Daher wurde in der vorliegenden Arbeit die Idee entwickelt, die morphologischen Informationen des 3D-Ultraschalls (3D-US) für Untersuchungen an Kleintieren zu verwenden, außerdem sollten Methoden zur multimodalen Bildgebung und Bildfusion von 3D-US und Kleintier-Positronenemissionstomographie (PET) entwickelt werden. Der Vorteil des Ultraschalls gegenüber dem Kleintier-CT liegt in der fehlenden Strahlenbelastung und der guten Verfügbarkeit, was besonders für Verlaufsstudien von Interesse ist. Methoden und Ergebnisse: Zur Bildoptimierung wurde ein Fadenphantom entwickelt, welches aufgrund der feinen Strukturen die qualitative als auch quantitative Bestimmung der Auflösung ermöglicht. Die Vorarbeiten am Fadenphantom konnten exzellent die Probleme des 3D-Ultraschalls mit der achsenabhängigen Auflösung zeigen und ermöglichten eine schnelle Beurteilung der Bildqualität. Hier bestehen Einsatzmöglichkeiten in der Bewertung verschiedener Ultraschallgeräte bezüglich der Tauglichkeit für 3D-Datenaquisition. Zur reproduzierbaren Lagerung von Mäusen wurde eine Schallkopfführung ein sowohl für 3D-US als auch Kleintier-PET kompatibler Tierhalter entwickelt. Die Maus lag zur Untersuchung im angewärmten Wasserbad auf dem Tierhalter fixiert, mit Inhalationsanästhesie und Sauerstoff über eine Atemmaske versorgt. Der Zeitaufwand für eine 3D-US-Untersuchung betrug für die Akquisition etwa eine Minute. Die generierten Ultraschalldatensätze waren von guter Qualität, Strukturen wie Leber, Nieren, Blase, Wirbelsäule und Lunge konnten selbst bei kleinen Mäusen von unter 20 Gramm Körpergewicht gut dargestellt werden. Zur Validierung des 3D-Ultraschalls wurde das Volumen verschiedener Organe und Tumore bestimmt und mit dem Goldstandard verglichen. Um die Koregistrierung mit der Kleintier-PET zu ermöglichen, wurden auf dem Tierhalter drei „fiducial markers“ angebracht, die Position und Orientierung eindeutig definieren. Die Kleintier-PET-Untersuchungen wurden nach standardisierten Protokollen durchgeführt. Die anschließende Bildfusion erfolgte mittels der frei verfügbaren Software "Amide". Diskussion: Mit dem in dieser Arbeit beschriebenen Verfahren ist eine standardisierte Gewinnung von 3D-US-Datensätzen an Kleintieren möglich; zusätzlich konnte die Machbarkeit der Bildfusion mit PET-Datensätzen gezeigt werden. Der Einsatz des 3D-Ultraschalls in longitudinalen Studien, zum Beispiel zur Beurteilung der Tumorprogression, ist vorstellbar. Die Zuverlässigkeit der volumetrischen Berechnungen ist für größere Organvolumina gut, bei kleineren Volumina besteht noch Optimierungsbedarf. Weitere Verbesserungen könnten durch den Einsatz von speziellen Schallköpfen und höheren Schallfrequenzen erzielt werden. N2 - Introduction: Ultrasound has been used for more than 50 years in medicine and has become a indispensable diagnostic tool, it allows a non-invasive imaging of the morphology and function of organs in real time. Small animal morphological imaging is now dominated by CT and MRI. For present study the idea to use morphological information of the 3D-ultrasound for examination of small animals was developed, these data should be used for image fusion of 3D ultrasound and small-animal PET. The advantage of ultrasound compared to the small-animal CT is the lack of radiation exposure and the good availability, which is especially for longitudinal studies of interest. Methods and Results: For image enhancement, a thread phantom was developed, fine structures facilitate qualitative and quantitative analysis of spatial resolution. Preliminary work on the thread phantom was excellent for investigate problems of 3D ultrasound with the axis-dependent resolution. There are potential applications for evaluating different ultrasonic devices in their suitability for 3D data acquisition. For the reproducible bedding of mice a guide bar for ultrasound transducer and a compatible holder for 3D-US and PET was developed. The mouse was bedded in the heated water bath fixed to the holder, applied inhalation anesthesia and oxygen through a breathing mask. The time required for a 3D ultrasound examination was for the acquisition of about one minute. The generated ultrasound data sets were of good quality, structures such as liver, kidney, bladder, spine and lungs were even in the case of small mice of 20 gram well represented. For validation of the 3D ultrasound volumes of various organs and tumors were determined and compared with gold standard. To allow coregistration with the microPET, three "fiducial markers" were attached to define the position and orientation. PET studies were performed according to standardized protocols. The subsequent image fusion was performed using the software "amide”. Discussion: In this study a standardized procedure for 3D-US of small animals was developed, in addition, the feasibility of image fusion with PET data sets was shown. The use of 3D ultrasound in longitudinal studies, for example, to assess tumor progression, is conceivable. The reliability of the volumetric calculations is good for large organ volumes, with smaller volumes, there is still need for improvement. Further improvements could be achieved through the use of special transducers and higher ultrasound frequencies. KW - Ultraschalldiagnostik KW - Nuklearmedizin KW - Würzburg / Klinik und Poliklinik für Nuklearmedizin KW - Molekulare Bildgebung KW - 3D-Ultraschall KW - dreidimensionaler Ultraschall KW - PET KW - Positronenemissionstomographie KW - Bildfusion KW - 3D ultrasound KW - three-dimensional ultrasound KW - PET KW - positron emission tomography KW - image fusion Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-55916 ER -