@article{WeigertPietrzykMuelleretal., author = {Weigert, Markus and Pietrzyk, Uwe and M{\"u}ller, Stefan P. and Palm, Christoph and Beyer, Thomas}, title = {Whole-body PET/CT imaging}, series = {Zeitschrift f{\"u}r Medizinische Physik}, volume = {18}, journal = {Zeitschrift f{\"u}r Medizinische Physik}, number = {1}, doi = {10.1016/j.zemedi.2007.07.004}, pages = {59 -- 66}, abstract = {Aim Combined whole-body (WB) PET/CT imaging provides better overall co-registration compared to separate CT and PET. However, in clinical routine local PET-CT mis-registration cannot be avoided. Thus, the reconstructed PET tracer distribution may be biased when using the misaligned CT transmission data for CT-based attenuation correction (CT-AC). We investigate the feasibility of retrospective co-registration techniques to align CT and PET images prior to CT-AC, thus improving potentially the quality of combined PET/CT imaging in clinical routine. Methods First, using a commercial software registration package CT images were aligned to the uncorrected PET data by rigid and non-rigid registration methods. Co-registration accuracy of both alignment approaches was assessed by reviewing the PET tracer uptake patterns (visual, linked cursor display) following attenuation correction based on the original and co-registered CT. Second, we investigated non-rigid registration based on a prototype ITK implementation of the B-spline algorithm on a similar targeted MR-CT registration task, there showing promising results. Results Manual rigid, landmark-based co-registration introduced unacceptable misalignment, in particular in peripheral areas of the whole-body images. Manual, non-rigid landmark-based co-registration prior to CT-AC was successful with minor loco-regional distortions. Nevertheless, neither rigid nor non-rigid automatic co-registration based on the Mutual Information image to image metric succeeded in co-registering the CT and noAC-PET images. In contrast to widely available commercial software registration our implementation of an alternative automated, non-rigid B-spline co-registration technique yielded promising results in this setting with MR-CT data. Conclusion In clinical PET/CT imaging, retrospective registration of CT and uncorrected PET images may improve the quality of the AC-PET images. As of today no validated and clinically viable commercial registration software is in routine use. This has triggered our efforts in pursuing new approaches to a validated, non-rigid co-registration algorithm applicable to whole-body PET/CT imaging of which first results are presented here. This approach appears suitable for applications in retrospective WB-PET/CT alignment. Ziel Kombinierte PET/CT-Bildgebung erm{\"o}glicht verbesserte Koregistrierung von PET- und CT-Daten gegen{\"u}ber separat akquirierten Bildern. Trotzdem entstehen in der klinischen Anwendung lokale Fehlregistrierungen, die zu Fehlern in der rekonstruierten PET- Tracerverteilung f{\"u}hren k{\"o}nnen, falls die unregistrierten CT-Daten zur Schw{\"a}chungskorrektur (AC) der Emissionsdaten verwendet werden. Wir untersuchen daher die Anwendung von Bildregistrierungsalgorithmen vor der CT-basierten AC zur Verbesserung der PET-Aufnahmen. Methoden Mittels einer kommerziellen Registrierungssoftware wurden die CT-Daten eines PET/CT- Tomographen durch landmarken- und intensit{\"a}tsbasierte rigide (starre) und nicht-rigide Registrierungsverfahren r{\"a}umlich an die unkorrigierten PET-Emissionsdaten angepasst und zur AC verwendet. Zur Bewertung wurden die Tracerverteilungen in den PET-Bildern (vor AC, CT-AC, CT-AC nach Koregistrierung) visuell und mit Hilfe korrelierter Fadenkreuze verglichen. Zus{\"a}tzlich untersuchten wir die ITK-Implementierung der bekannten B-spline basierten, nicht-rigiden Registrierungsans{\"a}tze im Hinblick auf ihre Verwendbarkeit f{\"u}r die multimodale PET/CT-Ganzk{\"o}rperregistrierung. Ergebnisse Mittels landmarkenbasierter, nicht-rigider Registrierung konnte die Tracerverteilung in den PET-Daten lokal verbessert werden. Landmarkenbasierte rigide Registrierung f{\"u}hrte zu starker Fehlregistrierung in entfernten K{\"o}rperregionen. Automatische rigide und nicht-rigide Registrierung unter Verwendung der Mutual-Information-{\"A}hnlichkeitsmetrik versagte auf allen verwendeten Datens{\"a}tzen. Die automatische Registrierung mit B-spline-Funktionen zeigte vielversprechende Resultate in der Anwendung auf einem {\"a}hnlich gelagerten CT-MR-Registrierungsproblem. Fazit Retrospektive, nicht-rigide Registrierung unkorrigierter PET- und CT-Aufnahmen aus kombinierten Aufnahmensystemen vor der AC kann die Qualit{\"a}t von PET-Aufnahmen im klinischen Einsatz verbessern. Trotzdem steht bis heute im klinischen Alltag keine validierte, automatische Registrierungssoftware zur Verf{\"u}gung. Wir verfolgen dazu Ans{\"a}tze f{\"u}r validierte, nicht-rigide Bildregistrierung f{\"u}r den klinischen Einsatz und pr{\"a}sentieren erste Ergebnisse.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @misc{RoserMeinikheimMendeletal., author = {Roser, David and Meinikheim, Michael and Mendel, Robert and Palm, Christoph and Probst, Andreas and Muzalyova, Anna and Scheppach, Markus W. and Nagl, Sandra and Schnoy, Elisabeth and R{\"o}mmele, Christoph and Schulz, Dominik Andreas Helmut Otto and Schlottmann, Jakob and Prinz, Friederike and Rauber, David and R{\"u}ckert, Tobias and Matsumura, Tomoaki and Fernandez-Esparrach, G. and Parsa, Nasim and Byrne, Michael F. and Messmann, Helmut and Ebigbo, Alanna}, title = {Human-Computer Interaction: Impact of Artificial Intelligence on the diagnostic confidence of endoscopists assessing videos of Barrett's esophagus}, series = {Endoscopy}, volume = {56}, journal = {Endoscopy}, number = {S 02}, publisher = {Georg Thieme Verlag}, issn = {1438-8812}, doi = {10.1055/s-0044-1782859}, pages = {79}, abstract = {Aims Human-computer interactions (HCI) may have a relevant impact on the performance of Artificial Intelligence (AI). Studies show that although endoscopists assessing Barrett's esophagus (BE) with AI improve their performance significantly, they do not achieve the level of the stand-alone performance of AI. One aspect of HCI is the impact of AI on the degree of certainty and confidence displayed by the endoscopist. Indirectly, diagnostic confidence when using AI may be linked to trust and acceptance of AI. In a BE video study, we aimed to understand the impact of AI on the diagnostic confidence of endoscopists and the possible correlation with diagnostic performance. Methods 22 endoscopists from 12 centers with varying levels of BE experience reviewed ninety-six standardized endoscopy videos. Endoscopists were categorized into experts and non-experts and randomly assigned to assess the videos with and without AI. Participants were randomized in two arms: Arm A assessed videos first without AI and then with AI, while Arm B assessed videos in the opposite order. Evaluators were tasked with identifying BE-related neoplasia and rating their confidence with and without AI on a scale from 0 to 9. Results The utilization of AI in Arm A (without AI first, with AI second) significantly elevated confidence levels for experts and non-experts (7.1 to 8.0 and 6.1 to 6.6, respectively). Only non-experts benefitted from AI with a significant increase in accuracy (68.6\% to 75.5\%). Interestingly, while the confidence levels of experts without AI were higher than those of non-experts with AI, there was no significant difference in accuracy between these two groups (71.3\% vs. 75.5\%). In Arm B (with AI first, without AI second), experts and non-experts experienced a significant reduction in confidence (7.6 to 7.1 and 6.4 to 6.2, respectively), while maintaining consistent accuracy levels (71.8\% to 71.8\% and 67.5\% to 67.1\%, respectively). Conclusions AI significantly enhanced confidence levels for both expert and non-expert endoscopists. Endoscopists felt significantly more uncertain in their assessments without AI. Furthermore, experts with or without AI consistently displayed higher confidence levels than non-experts with AI, irrespective of comparable outcomes. These findings underscore the possible role of AI in improving diagnostic confidence during endoscopic assessment.}, language = {en} } @misc{ZellmerRauberProbstetal., author = {Zellmer, Stephan and Rauber, David and Probst, Andreas and Weber, Tobias and Braun, Georg and Nagl, Sandra and R{\"o}mmele, Christoph and Schnoy, Elisabeth and Birzle, Lisa and Aehling, Niklas and Schulz, Dominik Andreas Helmut Otto and Palm, Christoph and Messmann, Helmut and Ebigbo, Alanna}, title = {K{\"u}nstliche Intelligenz als Hilfsmittel zur Detektion der Papilla duodeni major und des papill{\"a}ren Ostiums w{\"a}hrend der ERCP}, series = {Zeitschrift f{\"u}r Gastroenterologie}, volume = {63}, journal = {Zeitschrift f{\"u}r Gastroenterologie}, number = {5}, publisher = {Thieme}, address = {Stuttgart}, doi = {10.1055/s-0045-1806882}, pages = {e295}, abstract = {Einleitung Die Endoskopische Retrograde Cholangiopankreatikographie (ERCP) ist der Goldstandard in der endoskopischen Therapie von Erkrankungen des pankreatobili{\"a}ren Trakts. Allerdings ist sie technisch anspruchsvoll, schwer zu erlernen und mit einer relativ hohen Komplikationsrate assoziiert. Daher soll in der vorliegenden Machbarkeitsstudie gepr{\"u}ft werden, ob mithilfe eines Deeplearning- Algorithmus die Papille und das Ostium zuverl{\"a}ssig detektiert werden k{\"o}nnen und dieser f{\"u}r Endoskopiker, insbesondere in der Ausbildungssituation, ein geeignetes Hilfsmittel darstellen k{\"o}nnte. Material und Methodik Insgesamt wurden 1534 ERCP-Bilder von 134 Patienten analysiert, wobei sowohl die Papilla duodeni major als auch das Ostium segmentiert wurden. Anschließend erfolgte das Training eines neuronalen Netzes unter Verwendung eines Deep-Learning-Algorithmus. F{\"u}r den Test des Algorithmus erfolgte eine f{\"u}nffache Kreuzvalidierung. Ergebnisse Auf den 1534 gelabelten Bildern wurden f{\"u}r die Klasse Papille ein F1-Wert von 0,7996, eine Sensitivit{\"a}t von 0,8488 und eine Spezifit{\"a}t von 0,9822 erzielt. F{\"u}r die Klasse Ostium ergaben sich ein F1-Wert von 0,5198, eine Sensitivit{\"a}t von 0,5945 und eine Spezifit{\"a}t von 0,9974. Klassen{\"u}bergreifend (Klasse Papille und Klasse Ostium) betrug der F1-Wert 0,6593, die Sensitivit{\"a}t 0,7216 und f{\"u}r die Spezifit{\"a}t 0,9898. Zusammenfassung In der vorliegenden Machbarkeitsstudie zeigte das neuronale Netz eine hohe Sensitivit{\"a}t und eine sehr hohe Spezifit{\"a}t bei der Identifikation der Papilla duodeni major. Die Detektion des Ostiums erfolgte hingegen mit einer deutlich geringeren Sensitivit{\"a}t. Zuk{\"u}nftig ist eine Erweiterung des Trainingsdatensatzes um Videos und klinische Daten vorgesehen, um die Leistungsf{\"a}higkeit des Netzwerks zu verbessern. Hierdurch k{\"o}nnte langfristig ein geeignetes Assistenzsystem f{\"u}r die ERCP, insbesondere in der Ausbildungssituation etabliert werden.}, language = {de} } @article{DehnhardtPalmVietenetal., author = {Dehnhardt, Markus and Palm, Christoph and Vieten, Andrea and Bauer, Andreas and Pietrzyk, Uwe}, title = {Quantifying the A1AR distribution in peritumoral zones around experimental F98 and C6 rat brain tumours}, series = {Journal of Neuro-Oncology}, volume = {85}, journal = {Journal of Neuro-Oncology}, doi = {10.1007/s11060-007-9391-6}, pages = {49 -- 63}, abstract = {Quantification of growth in experimental F98 and C6 rat brain tumours was performed on 51 rat brains, 17 of which have been further assessed by 3D tumour reconstruction. Brains were cryosliced and radio-labelled with a ligand of the peripheral type benzodiazepine-receptor (pBR), 3H-Pk11195 [(1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propylene)-3-isoquinoline-carboxamide)] by receptor autoradiography. Manually segmented and automatically registered tumours have been 3D-reconstructed for volumetric comparison on the basis of 3H-Pk11195-based tumour recognition. Furthermore automatically computed areas of -300 μm inner (marginal) zone as well as 300 μm and 600 μm outer tumour space were quantified. These three different regions were transferred onto other adjacent slices that had been labelled by receptor autoradiography with the A1 Adenosine receptor (A1AR)-ligand 3H-CPFPX (3H-8-cyclopentyl-3-(3-fluorpropyl)-1-propylxanthine) for quantitative assessment of A1AR in the three different tumour zones. Hence, a method is described for quantifying various receptor protein systems in the tumour as well as in the marginal invasive zones around experimentally implanted rat brain tumours and their representation in the tumour microenvironment as well as in 3D space. Furthermore, a tool for automatically reading out radio-labelled rat brain slices from auto radiographic films was developed, reconstructed into a consistent 3D-tumour model and the zones around the tumour were visualized. A1AR expression was found to depend upon the tumour volume in C6 animals, but is independent on the time of tumour development. In F98 animals, a significant increase in A1AR receptor protein was found in the Peritumoural zone as a function of time of tumour development and tumour volume.}, subject = {Hirntumor}, language = {en} } @article{MangSchnabelCrumetal., author = {Mang, Andreas and Schnabel, Julia A. and Crum, William R. and Modat, Marc and Camara-Rey, Oscar and Palm, Christoph and Caseiras, Gisele Brasil and J{\"a}ger, H. Rolf and Ourselin, S{\´e}bastien and Buzug, Thorsten M. and Hawkes, David J.}, title = {Consistency of parametric registration in serial MRI studies of brain tumor progression}, series = {International Journal of Computer Assisted Radiology and Surgery}, volume = {3}, journal = {International Journal of Computer Assisted Radiology and Surgery}, number = {3-4}, doi = {10.1007/s11548-008-0234-5}, pages = {201 -- 211}, abstract = {Object The consistency of parametric registration in multi-temporal magnetic resonance (MR) imaging studies was evaluated. Materials and methods Serial MRI scans of adult patients with a brain tumor (glioma) were aligned by parametric registration. The performance of low-order spatial alignment (6/9/12 degrees of freedom) of different 3D serial MR-weighted images is evaluated. A registration protocol for the alignment of all images to one reference coordinate system at baseline is presented. Registration results were evaluated for both, multimodal intra-timepoint and mono-modal multi-temporal registration. The latter case might present a challenge to automatic intensity-based registration algorithms due to ill-defined correspondences. The performance of our algorithm was assessed by testing the inverse registration consistency. Four different similarity measures were evaluated to assess consistency. Results Careful visual inspection suggests that images are well aligned, but their consistency may be imperfect. Sub-voxel inconsistency within the brain was found for allsimilarity measures used for parametric multi-temporal registration. T1-weighted images were most reliable for establishing spatial correspondence between different timepoints. Conclusions The parametric registration algorithm is feasible for use in this application. The sub-voxel resolution mean displacement error of registration transformations demonstrates that the algorithm converges to an almost identical solution for forward and reverse registration.}, subject = {Kernspintomografie}, language = {en} } @inproceedings{PalmGraemeCrumetal., author = {Palm, Christoph and Graeme, Penny P. and Crum, William R. and Schnabel, Julia A. and Pietrzyk, Uwe and Hawkes, David J.}, title = {Fusion of Rat Brain Histology and MRI using Weighted Multi-Image Mutual Information}, series = {Proceedings of the SPIE Medical Imaging 6914: Image Processing 69140M}, booktitle = {Proceedings of the SPIE Medical Imaging 6914: Image Processing 69140M}, number = {6914}, doi = {10.1117/12.770605}, pages = {69140M-1 -- 69140M-9}, abstract = {Fusion of histology and MRI is frequently demanded in biomedical research to study in vitro tissue properties in an in vivo reference space. Distortions and artifacts caused by cutting and staining of histological slices as well as differences in spatial resolution make even the rigid fusion a difficult task. State-of- the-art methods start with a mono-modal restacking yielding a histological pseudo-3D volume. The 3D information of the MRI reference is considered subsequently. However, consistency of the histology volume and consistency due to the corresponding MRI seem to be diametral goals. Therefore, we propose a novel fusion framework optimizing histology/histology and histology/MRI consistency at the same time finding a balance between both goals. Method - Direct slice-to-slice correspondence even in irregularly-spaced cutting sequences is achieved by registration-based interpolation of the MRI. Introducing a weighted multi-image mutual information metric (WI), adjacent histology and corresponding MRI are taken into account at the same time. Therefore, the reconstruction of the histological volume as well as the fusion with the MRI is done in a single step. Results - Based on two data sets with more than 110 single registrations in all, the results are evaluated quantitatively based on Tanimoto overlap measures and qualitatively showing the fused volumes. In comparison to other multi-image metrics, the reconstruction based on WI is significantly improved. We evaluated different parameter settings with emphasis on the weighting term steering the balance between intra- and inter-modality consistency.}, subject = {Kernspintomografie}, language = {en} } @article{DesernoHandelsMaierHeinetal., author = {Deserno, Thomas M. and Handels, Heinz and Maier-Hein, Klaus H. and Mersmann, Sven and Palm, Christoph and Tolxdorff, Thomas and Wagenknecht, Gudrun and Wittenberg, Thomas}, title = {Viewpoints on Medical Image Processing}, series = {Current Medical Imaging Reviews}, volume = {9}, journal = {Current Medical Imaging Reviews}, number = {2}, doi = {10.2174/1573405611309020002}, pages = {79 -- 88}, abstract = {Medical image processing provides core innovation for medical imaging. This paper is focused on recent developments from science to applications analyzing the past fifteen years of history of the proceedings of the German annual meeting on medical image processing (BVM). Furthermore, some members of the program committee present their personal points of views: (i) multi-modality for imaging and diagnosis, (ii) analysis of diffusion-weighted imaging, (iii) model-based image analysis, (iv) registration of section images, (v) from images to information in digital endoscopy, and (vi) virtual reality and robotics. Medical imaging and medical image computing is seen as field of rapid development with clear trends to integrated applications in diagnostics, treatment planning and treatment.}, subject = {Bildgebendes Verfahren}, language = {en} } @inproceedings{EibenKunzPietrzyketal., author = {Eiben, Bj{\"o}rn and Kunz, Dietmar and Pietrzyk, Uwe and Palm, Christoph}, title = {Level-Set-Segmentierung von Rattenhirn MRTs}, series = {Bildverarbeitung f{\"u}r die Medizin 2009; Algorithmen - Systeme - Anwendungen ; Proceedings des Workshops vom 22. bis 25. M{\"a}rz 2009 in Heidelberg}, booktitle = {Bildverarbeitung f{\"u}r die Medizin 2009; Algorithmen - Systeme - Anwendungen ; Proceedings des Workshops vom 22. bis 25. M{\"a}rz 2009 in Heidelberg}, publisher = {Springer}, address = {Berlin}, pages = {167 -- 171}, abstract = {In dieser Arbeit wird die Segmentierung von Gehirngewebe aus Kopfaufnahmen von Ratten mittels Level-Set-Methoden vorgeschlagen. Dazu wird ein zweidimensionaler, kontrastbasierter Ansatz zu einem dreidimensionalen, lokal an die Bildintensit{\"a}t adaptierten Segmentierer erweitert. Es wird gezeigt, dass mit diesem echten 3D-Ansatz die lokalen Bildstrukturen besser ber{\"u}cksichtigt werden k{\"o}nnen. Insbesondere Magnet-Resonanz-Tomographien (MRTs) mit globalen Helligkeitsgradienten, beispielsweise bedingt durch Oberfl{\"a}chenspulen, k{\"o}nnen auf diese Weise zuverl{\"a}ssiger und ohne weitere Vorverarbeitungsschritte segmentiert werden. Die Leistungsf{\"a}higkeit des Algorithmus wird experimentell an Hand dreier Rattenhirn-MRTs demonstriert.}, subject = {Dreidimensionale Bildverarbeitung}, language = {de} } @inproceedings{PietrzykPalmBeyer, author = {Pietrzyk, Uwe and Palm, Christoph and Beyer, Thomas}, title = {Investigation of fusion strategies of multi-modality images}, series = {IEEE Nuclear Science Symposium Conference Record}, volume = {4}, booktitle = {IEEE Nuclear Science Symposium Conference Record}, doi = {10.1109/NSSMIC.2004.1462740}, pages = {2399 -- 2401}, abstract = {Presenting images from different modalities seems to be a trivial task considering the challenges to obtain registered images as a pre-requisite for image fusion. In combined tomographs like PET/CT, image registration is intrinsic. However, informative image fusion mandates careful preparation owing to the large amount of information that is presented to the observer. In complex imaging situations it is required to provide tools that are easy to handle and still powerful enough to help the observer discriminating important details from background patterns. We investigated several options for color tables applied to brain and non-brain images obtained with PET, MRI and CT.}, language = {en} } @misc{BauerStoffelsPauleitetal., author = {Bauer, Dagmar and Stoffels, Gabriele and Pauleit, Dirk and Palm, Christoph and Hamacher, Kurt and Coenen, Heinz H. and Langen, Karl}, title = {Uptake of F-18-fluoroethyl-L-tyrosine and H-3-L-methionine in focal cortical ischemia}, series = {The Journal of Nuclear Medicine}, volume = {47}, journal = {The Journal of Nuclear Medicine}, number = {Suppl. 1}, pages = {284P}, abstract = {Objectives: C-11-methionine (MET) is particularly useful in brain tumor diagnosis but unspecific uptake e.g. in cerebral ischemia has been reported (1). The F-18-labeled amino acid O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) shows a similar clinical potential as MET in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of FET and H-3-MET in focal cortical ischemia in rats by dual tracer autoradiography. Methods: Focal cortical ischemia was induced in 12 Fisher CDF rats using the photothrombosis model (PT). One day (n=3) , two days (n=5) and 7 days (n=4) after induction of the lesion FET and H-3-MET were injected intravenously. One hour after tracer injection animals were killed, the brains were removed immediately and frozen in 2-methylbutane at -50°C. Brains were cut in coronal sections (thickness: 20 µm) and exposed first to H-3 insensitive photoimager plates to measure FET distribution. After decay of F-18 the distribution of H-3-MET was determined. The autoradiograms were evaluated by regions of interest (ROIs) placed on areas with increased tracer uptake in the PT and the contralateral brain. Lesion to brain ratios (L/B) were calculated by dividing the mean uptake in the lesion and the brain. Based on previous studies in gliomas a L/B ratio > 1.6 was considered as pathological for FET. Results: Variable increased uptake of both tracers was observed in the PT and its demarcation zone at all stages after PT. The cut-off level of 1.6 for FET was exceeded in 9/12 animals. One day after PT the L/B ratios were 2.0 ± 0.6 for FET vs. 2.1 ± 1.0 for MET (mean ± SD); two days after lesion 2.2 ± 0.7 for FET vs. 2.7 ± 1.0 for MET and 7 days after lesion 2.4 ± 0.4 for FET vs. 2.4 ± 0.1 for MET. In single cases discrepancies in the uptake pattern of FET and MET were observed. Conclusions: FET like MET may exhibit significant uptake in infarcted areas or the immediate vincinity which has to be considered in the differential diagnosis of unkown brain lesions. The discrepancies in the uptake pattern of FET and MET in some cases indicates either differences in the transport mechanisms of both amino acids or a different affinity for certain cellular components.}, language = {en} } @article{MatuschDepboyluPalmetal., author = {Matusch, Andreas and Depboylu, Candan and Palm, Christoph and Wu, Bei and H{\"o}glinger, G{\"u}nter U. and Sch{\"a}fer, Martin K.-H. and Becker, Johanna Sabine}, title = {Cerebral bio-imaging of Cu, Fe, Zn and Mn in the MPTP mouse model of Parkinsons disease using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)}, series = {Journal of the American Society for Mass Spectrometry}, volume = {21}, journal = {Journal of the American Society for Mass Spectrometry}, number = {1}, doi = {10.1016/j.jasms.2009.09.022}, pages = {161 -- 171}, abstract = {Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful technique for the determination of metal and nonmetal distributions within biological systems with high sensitivity. An imaging LA-ICP-MS technique for Fe, Cu, Zn, and Mn was developed to produce large series of quantitative element maps in native brain sections of mice subchronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) as a model of Parkinson's disease. Images were calibrated using matrix-matched laboratory standards. A software solution allowing a precise delineation of anatomical structures was implemented. Coronal brain sections were analyzed crossing the striatum and the substantia nigra, respectively. Animals sacrificed 2 h, 7 d, or 28 d after the last MPTP injection and controls were investigated. We observed significant decreases of Cu concentrations in the periventricular zone and the fascia dentata at 2 h and 7d and a recovery or overcompensation at 28 d, most pronounced in the rostral periventricular zone (+40\%). In the cortex Cu decreased slightly to -10\%. Fe increased in the interpeduncular nucleus (+40\%) but not in the substantia nigra. This pattern is in line with a differential regulation of periventricular and parenchymal Cu, and with the histochemical localization of Fe, and congruent to regions of preferential MPTP binding described in the rodent brain. The LA-ICP-MS technique yielded valid and statistically robust results in the present study on 39 slices from 19 animals. Our findings underline the value of routine micro-local analytical techniques in the life sciences and affirm a role of Cu availability in Parkinson's disease.}, subject = {ICP-Massenspektrometrie}, language = {en} } @article{BeckerMatuschBeckeretal., author = {Becker, Johanna Sabine and Matusch, Andreas and Becker, Julia Susanne and Wu, Bei and Palm, Christoph and Becker, Albert Johann and Salber, Dagmar}, title = {Mass spectrometric imaging (MSI) of metals using advanced BrainMet techniques for biomedical research}, series = {International Journal of Mass Spectrometry}, volume = {307}, journal = {International Journal of Mass Spectrometry}, number = {1-3}, publisher = {eLSEVIER}, address = {Elsevier}, doi = {10.1016/j.ijms.2011.01.015}, pages = {3 -- 15}, abstract = {Mass spectrometric imaging (MSI) is a young innovative analytical technique and combines different fields of advanced mass spectrometry and biomedical research with the aim to provide maps of elements and molecules, complexes or fragments. Especially essential metals such as zinc, copper, iron and manganese play a functional role in signaling, metabolism and homeostasis of the cell. Due to the high degree of spatial organization of metals in biological systems their distribution analysis is of key interest in life sciences. We have developed analytical techniques termed BrainMet using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to measure the distribution of trace metals in biological tissues for biomedical research and feasibility studies—including bioaccumulation and bioavailability studies, ecological risk assessment and toxicity studies in humans and other organisms. The analytical BrainMet techniques provide quantitative images of metal distributions in brain tissue slices which can be combined with other imaging modalities such as photomicrography of native or processed tissue (histochemistry, immunostaining) and autoradiography or with in vivo techniques such as positron emission tomography or magnetic resonance tomography. Prospective and instrumental developments will be discussed concerning the development of the metalloprotein microscopy using a laser microdissection (LMD) apparatus for specific sample introduction into an inductively coupled plasma mass spectrometer (LMD-ICP-MS) or an application of the near field effect in LA-ICP-MS (NF-LA-ICP-MS). These nano-scale mass spectrometric techniques provide improved spatial resolution down to the single cell level.}, subject = {Massenspektrometrie}, language = {en} } @article{BeckerMatuschPalmetal., author = {Becker, Johanna Sabine and Matusch, Andreas and Palm, Christoph and Salber, Dagmar and Morton, Kathryn A. and Becker, Julia Susanne}, title = {Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics}, series = {Metallomics}, journal = {Metallomics}, number = {2}, publisher = {Oxford Academic Press}, doi = {10.1039/b916722f}, pages = {104 -- 111}, abstract = {Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.}, subject = {ICP-Massenspektrometrie}, language = {en} } @article{OsterholtSalberMatuschetal., author = {Osterholt, Tobias and Salber, Dagmar and Matusch, Andreas and Becker, Johanna Sabine and Palm, Christoph}, title = {IMAGENA: Image Generation and Analysis}, series = {International Journal of Mass Spectrometry}, volume = {307}, journal = {International Journal of Mass Spectrometry}, number = {1-3}, doi = {10.1016/j.ijms.2011.03.010}, pages = {232 -- 239}, abstract = {Metals are involved in many processes of life. They are needed for enzymatic reactions, are involved in healthy processes but also yield diseases if the metal homeostasis is disordered. Therefore, the interest to assess the spatial distribution of metals is rising in biomedical science. Imaging metal (and non-metal) isotopes by laser ablation mass spectrometry with inductively coupled plasma (LA-ICP-MS) requires a special software solution to process raw data obtained by scanning a sample line-by-line. As no software ready to use was available we developed an interactive software tool for Image Generation and Analysis (IMAGENA). Unless optimised for LA-ICP-MS, IMAGENA can handle other raw data as well. The general purpose was to reconstruct images from a continuous list of raw data points, to visualise these images, and to convert them into a commonly readable image file format that can be further analysed by standard image analysis software. The generation of the image starts with loading a text file that holds a data column of every measured isotope. Specifying general spatial domain settings like the data offset and the image dimensions is done by the user getting a direct feedback by means of a preview image. IMAGENA provides tools for calibration and to correct for a signal drift in the y-direction. Images are visualised in greyscale as well a pseudo-colours with possibilities for contrast enhancement. Image analysis is performed in terms of smoothed line plots in row and column direction.}, subject = {ICP-Massenspektrometrie}, language = {en} }