Deep learning reconstruction improves radiomics feature stability and discriminative power in abdominal CT imaging: a phantom study

Objectives: To compare image quality of deep learning reconstruction (AiCE) for radiomics feature extraction with filtered back projection (FBP), hybrid iterative reconstruction (AIDR 3D), and model-based iterative reconstruction (FIRST). Methods: Effects of image reconstruction on radiomics features were investigated using a phantom that realistically mimicked a 65-year-old patient's abdomen with hepatic metastases. The phantom was scanned at 18 doses from 0.2 to 4 mGy, with 20 repeated scans per dose. Images were reconstructed with FBP, AIDR 3D, FIRST, and AiCE. Ninety-three radiomics features were extracted from 24 regions of interest, which were evenly distributed across three tissue classes: normal liver, metastatic core, and metastatic rim. Features were analyzed in terms of their consistent characterization of tissues within the same image (intraclass correlation coefficient >= 0.75), discriminative power (Kruskal-Wallis test p value = 0.75). Results: The median fraction of consistent features across all doses was 6%, 8%, 6%, and 22% with FBP, AIDR 3D, FIRST, and AiCE, respectively. Adequate discriminative power was achieved by 48%, 82%, 84%, and 92% of features, and 52%, 20%, 17%, and 39% of features were repeatable, respectively. Only 5% of features combined consistency, discriminative power, and repeatability with FBP, AIDR 3D, and FIRST versus 13% with AiCE at doses above 1 mGy and 17% at doses >= 3 mGy. AiCE was the only reconstruction technique that enabled extraction of higher-order features. Conclusions: AiCE more than doubled the yield of radiomics features at doses typically used clinically. Inconsistent tissue characterization within CT images contributes significantly to the poor stability of radiomics features

Reliability of NI-RADS criteria in the interpretation of contrast-enhanced magnetic resonance imaging considering the potential role of diffusion-weighted imaging

Objectives: To assess inter- and intrareader agreement of the Neck Imaging Reporting and Data System (NI-RADS) used in contrast-enhanced magnetic resonance imaging (MRI) including analysis of diffusion-weighted imaging (DWI), which is currently not part of the NI-RADS criteria. Methods: This retrospective study included anonymized surveillance contrast-enhanced MRI datasets of 104 patients treated for different head and neck cancers. Three radiologists experienced in head and neck imaging reported findings for the primary site and the neck using NI-RADS criteria in a first step and evaluated DWI sequences for the primary site in a second step. Thirty randomly selected imaging datasets were again presented to the readers. Kappa statistics and observed agreement (A(o)) were calculated. Results: Interreader agreement across all MRI datasets was moderate (kappa(Fleiss) = 0.53) for NI-RADS categories assigned to the primary site, substantial for NI-RADS categories of the neck (kappa(Fleiss) = 0.67), and almost perfect for DWI of the primary site (kappa(Fleiss) = 0.83). Interreader agreement for the primary site was particularly low in cases of cancer recurrence (kappa(Fleiss) = 0.35) and when categories 2a, 2b, and 3 were combined (kappa(Fleiss) = 0.30). Intrareader agreement was considerably lower for NI-RADS categories of the primary site (range A(o) = 53.3-70.0%) than for NI-RADS categories of the neck (range A(o) = 83.3-90.0%) and DWI of the primary site (range A(o) = 93.3-100.0%). Conclusion: Interreader agreement of NI-RADS for reporting contrast-enhanced MRI findings is acceptable for the neck but limited for the primary site. Here, DWI has the potential to serve as a reliable additional criterion

Perivascular vital cells in the ablation center after multibipolar radiofrequency ablation in an in vivo porcine model

Multibipolar radiofrequency ablation (RFA) is an advanced ablation technique for early stage hepatocellular carcinoma and liver metastases. Vessel cooling in multibipolar RFA has not been systematically investigated. The objective of this study was to evaluate the presence of perivascular vital cells within the ablation zone after multibipolar RFA. Multibipolar RFA were performed in domestic pigs in vivo. Three internally cooled bipolar RFA applicators were used simultaneously. Three experimental settings were planned: (1) inter-applicator-distance: 15 mm; (2) inter-applicator-distance: 20 mm; (3) inter-applicator-distance: 20 mm with hepatic inflow occlusion (Pringle maneuver). A vitality staining was used to analyze liver cell vitality around all vessels in the ablation center with a diameter>0.5 mm histologically. 771 vessels were identified. No vital tissue was seen around 423 out of 429 vessels (98.6%) situated within the central white zone. Vital cells could be observed around major hepatic vessels situated adjacent to the ablation center. Vessel diameter (>3.0 mm; p<0.05) and low vessel-to-ablation-center distance (<0.2 mm; p<0.05) were identified as risk factors for incomplete ablation adjacent to hepatic vessels. The vast majority of vessels, which were localized in the clinically relevant white zone, showed no vital perivascular cells, regardless of vessel diameter and vessel type. However, there was a risk of incomplete ablation around major hepatic vessels situated directly within the ablation center. A Pringle maneuver could avoid incomplete ablations

Deep learning for detection of radiographic sacroiliitis: achieving expert-level performance

Background: Radiographs of the sacroiliac joints are commonly used for the diagnosis and classification of axial spondyloarthritis. The aim of this study was to develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of axial spondyloarthritis (axSpA). Methods: Conventional radiographs of the sacroiliac joints obtained in two independent studies of patients with axSpA were used. The first cohort comprised 1553 radiographs and was split into training (n = 1324) and validation (n = 229) sets. The second cohort comprised 458 radiographs and was used as an independent test dataset. All radiographs were assessed in a central reading session, and the final decision on the presence or absence of definite radiographic sacroiliitis was used as a reference. The performance of the neural network was evaluated by calculating areas under the receiver operating characteristic curves (AUCs) as well as sensitivity and specificity. Cohen's kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers. Results: The neural network achieved an excellent performance in the detection of definite radiographic sacroiliitis with an AUC of 0.97 and 0.94 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 88% and 95% for the validation and 92% and 81% for the test set. The Cohen's kappa between the neural network and the reference judgements were 0.79 and 0.72 for the validation and test sets with an absolute agreement of 90% and 88%, respectively. Conclusion: Deep artificial neural networks enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.</p

Application of computed tomography volume datasets with combined 2D and 3D reconstructions in animal experiments reflecting the 3R concept

In dieser Habilitationsarbeit wurde untersucht, inwiefern der Einsatz der Computertomographie mit nachfolgenden 2D- und 3D-Reformatierungen einen Beitrag in Tierexperimenten und zu dem 3R-Konzept in Form einer Verringerung, Verfeinerung und Vermeidung von Tierversuchen leisten kann. Gerade computertomographische Untersuchungen besitzen aufgrund der kurzen Akquisitionszeit einen hohen Wert bei der umfassenden Auswertung von tierexperimentellen Versuchsvorhaben. Die risikoarme Darstellung des Versuchstieres mittels CT sowie die Nachverarbeitung der Volumendatensätze ermöglicht die Beantwortung von Fragen weit über die initiale Fragestellung hinaus. Die hier dargestellten Arbeiten belegen den Wert der CT für tierexperimentelle Studien und in den Bereichen Vermeidung, Verfeinerung und Verringerung nach den 3R-Prinzipien von Russel und Burch: So konnten pulmonale Veränderungen mittels CT nachgewiesen werden, die den Einfluss unphysiologischer Positionierung auf Lungenperfusion und-ventilation wiederspiegelt (s. Seite 13). Ebenso konnten bildmorphologisch die Einschränkungen bei der venovenösen Haemofiltration erklärt und Alternativen aufgezeigt werden (s. Seite 23). Zur Verfeinerung des Tiermodells „Minipig“ wurden die zentralen Gefäße in vivo mittels CT zu verschiedenen Zeitpunkten gemessen und zur Histologie korreliert. Damit wurde erstmalig ein Datenpool generiert, der ohne Einschränkung von Fixierung und Schrumpfung das wiederspiegelt, was intraoperativ oder interventionell vorgefunden werden wird (s. Seite 35). Zudem konnte der Einfluss von Gewicht und Wachstum auf das Gefäßsystem von Minipigs im untersuchten Alter zwischen 16 und 20 Monaten relativiert werden. Die Evaluation einer Venenmanschette, die auf Ortsständigkeit, Funktion und Biokompatibilität getestet wurde, greift bis zum Finaltag ausschließlich auf CT-Datensätze zurück. Aufgrund des Einsatzes der CT konnten alle wesentlichen Fragen im Verlauf des Versuches ohne serielle Tötung der Tiere beantwortet werden. Der Aspekt der Verringerung (weniger Tiere zur vollständigen Beantwortung der Hypothesen) konnte hier aufgegriffen und erfolgreich umgesetzt werden (s. Seite 40). Zwei Aspekte physiologischer und pathophysiologischer Veränderungen wurden erfolgreich mittels computertomographischer Volumendatensätze dargestellt: So wurde nachgewiesen und bildmorphologisch aufgearbeitet, dass -und wie- ein vollständiger Verschluss der Aorta bei weiblichen Hausschweinen aufgrund stark ausgeprägter Kollateralkreisläuft weitestgehend ohne klinische Symptome kompensiert werden kann (s. Seite 51). Zuletzt wurde durch die Betrachtung von Knochendefekten am Unterkiefer von Minipigs das Konzept der kritischen Defektgröße in Frage gestellt. Bei unterschiedlichen Defektgrößen weit über der als kritisch betrachteten Defektgröße zeigte sich im CT und auch volumetrisch eine ausgedehnte Knochenneubildung (s. Seite 65). Gleichzeitig konnten in dieser Studie auch die Limitationen eines Tiermodelles und die Folgen artspezifischer Besonderheiten aufgegriffen und bildmorphologisch belegt werden. Das hier gewonnen Wissen kann zur Vermeidung von eingeschränkt-aussagekräftigen Versuchsvorhaben eingesetzt werden, da diese Daten einmal mehr zeigen, dass ein an sich etabliertes Tiermodell aufgrund unzureichender physiologischer Deskription kritisch hinterfragt werden muss. Zuletzt ermöglicht ein Datenpool aus allen durchgeführten Studien an Hausschweinen und Minipigs eine Auswertung der Datensätze mit neuen Fragestellungen ohne weitere Versuche oder Messungen. Beispielhaft sei hier auf Originalarbeit 3 verwiesen, die ohne zusätzliche Untersuchungen auskommt und sich auf die vorhandenen Daten des Bildarchives stützt. Fragestellungen zum muskuloskelettalen System, zu Reifung und Wachstum können aus einem solchen Pool beispielsweise beantwortet oder geplante Versuchsvorhaben optimiert werden. Der Einsatz bildgebender Verfahren bietet somit ein Potential, welches weit über die initialen Fragestellungen eines Versuches hinausgeht.This habilitation thesis investigated how the use of computed tomography (CT) with subsequent 2D and 3D reformations can contribute in animal experiments and to the 3R concept in terms of reduction, refinement and replacement. Especially computed tomographic scans have a high value in the comprehensive analysis of animal experimental projects due to the short acquisition time. The low-risk imaging of the animal by CT and postprocessing of the acquired volume data sets make it possible to answer questions even far beyond the initial question. The habilitation thesis presented here demonstrates the value of CT for animal studies and especially in the areas of replacement, reduction and refinement according to the 3R principles of Russell and Burch: We could detect pulmonary changes on CT representing influence of non- physiological positioning on lung perfusion and ventilation (see page 13). Also we were able to image the reasons for limitations of veno-venous hemofiltration and present alternatives (see page 23). For refinement of the animal model "Minipig" the central vessels were measured in vivo by CT at different time points and then correlated to histology. For the first time a data pool was generated, which -without restriction of fixation and shrinkage- is comparable to what will be encountered during surgery or interventional procedures (see page 35). Furthermore, the influence of weight and growth on the vascular system of minipigs aged between 16-20 months could be relativized. The evaluation of a vein cuff, which has been tested according its position, function and biocompatibility, was done exclusively on CT data sets. With the help of CT most of the questions could be answered during the course of the trial without killing the animals. The aspect of reduction (less animals) was successfully implemented here (see page 40). Two aspects of physiological and pathophysiological changes were successfully represented by means of computed tomographic volume data sets : It has been shown that -and how- a complete occlusion of the aorta can be completely compensated without clinical symptoms in female domestic pigs due to specific collaterals (see page 51). Finally, the concept of the critical defect size was called into question observating bone defects in the mandible of minipigs. Different defect sizes far beyond the size considered as critical showed extensive new bone formation in CT and in volumetric assessment (see page 65). At the same time the limitations of an animal model and the consequences were addressed in this study. The knowledge gained here can be used to prevent experimental projects, as these data shows once again that a well-established animal models need to be examined further because of insufficient physiological description. Additionally, a pool of data acquired from all studies in domestic pigs and minipigs enables further evaluation with new questions and without further scans or measurements. For example, one given publication did not require any additional animal testing but was based on the existing data of the image archive. Questions on musculoskeletal system, maturation and growth, for example, can be answered or planned and optimized from such a data pool. Imaging techniques like CT provide a potential that goes far beyond answering the initial questions of a trial

Stellenwert der Bildfusion von Positronenemissionstomographie und Computertomographie bei onkologischen Erkrankungen des Pankreas

Die Detektion des Pankreaskarzinoms oder die Unterscheidung zwischen einem Karzinom und einer chronischen Pankreatitis bleibt ein diagnostisches Problem. Jedes bisher eingesetzte bildgebende Verfahren hat seine Vor- und Nachteile. Die Bildfusion macht sich die verschiedenen Stärken und Schwächen der einzelnen Bildgebungen zum Vorteil und kombiniert diese mit dem Ziel, die Stärken zu addieren und die Schwächen zu reduzieren. In dieser Arbeit werden Bilder der CT und der Positronenemissionstomographie miteinander kombiniert, um sowohl eine hohe anatomische Auflösung zu erreichen als auch auf Stoffwechseleigenschaften des Gewebes zurückgreifen zu können. Die Auswertung ergab, dass die Bildfusion hinsichtlich der Karzinomdetektion der CT und der PET überlegen ist. Auch für Umgebungsinfiltration, Lymphknotenbefall und Fernmetastasen ergab die Auswertung bessere Ergebnisse als für die jeweiligen Einzelmodalitäten. Die Bildfusion kann die Akkuratheit der verschiedenen Untersuchungen verbessern und ohne technisch großen Aufwand wie auch ohne weitere Patientenbelastung um wertvolle Information ergänzen. Damit stellt die Bildfusion eine wertvolle Methode zur Erkennung und Visualisierung vor allem kleiner und schwer zu lokalisierender Neoplasien dar. Ebenfalls bietet sie eine genaue Möglichkeit zur Biopsie- und Bestrahlungsplanung.The differentiation between pancreatic carcinoma and inflammatory pancreatic diseases remains a diagnostic problem. Every imaging method available has its own lack of information. Image-fusion uses the strength and the disadvantage of each imaging method. Trough the combination of the images advantages are combined whereas the disadvantages are reduced. In this study images of CT and PET were fused to archive a high anatomic resolution and the information about tissue metabolism. The evaluation showed the superiority of fused images in comparison to the single modalities regarding the detection of lesions, the infiltration of surrounding tissue and lymph nodes as well as detection of distant metastases. Image fusion improves accuracy of CT and PET without huge technical effort or patient-strain while providing useful accessory information. For this reason image-fusion presents a valuable method for detection and visualisation of particularly small lesions in early tumor stage. Furthermore it offers administrable information for biopsy and radiation-planning