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1. Motion Correction of 3D Dynamic Contrast-Enhanced Ultrasound Imaging without Anatomical Bmode Images

Author

Chen, Jia-Shu, D., Maged Goubran Ph., Kim, Gaeun, D., Jurgen K. Willmann M., D., Michael Zeineh M., D., Ph., D., Dimitre Hristov Ph., and D, Ahmed El Kaffas Ph.

Subjects
Electrical Engineering and Systems Science - Image and Video Processing
Abstract

In conventional 2D DCE-US, motion correction algorithms take advantage of accompanying side-by-side anatomical Bmode images that contain time-stable features. However, current commercial models of 3D DCE-US do not provide side-by-side Bmode images, which makes motion correction challenging. This work introduces a novel motion correction (MC) algorithm for 3D DCE-US and assesses its efficacy when handling clinical data sets. In brief, the algorithm uses a pyramidal approach whereby short temporal windows consisting of 3-6 consecutive frames are created to perform local registrations, which are then registered to a master reference derived from a weighted average of all frames. We evaluated the algorithm in 8 patients with metastatic lesions in the liver using the Philips X6-1 matrix transducer at a frame rate of 1-3 Hz. We assessed improvements in original vs. motion corrected 3D DCE-US cine using: i) frame-to-frame volumetric overlap of segmented lesions, ii) normalized correlation coefficient (NCC) between frames (similarity analysis), and iii) sum of squared errors (SSE), root-mean-squared error (RMSE), and r-squared (R2) quality-of-fit from fitted time-intensity curves (TIC) extracted from a segmented lesion. Overall, results demonstrate significant decreases in 3D DCE-US motion after applying the proposed algorithm. We noted significant improvements in frame-to-frame lesion overlap across all patients, from 68% without correction to 83% with motion correction (p = 0.023). Frame-to-frame similarity as assessed by NCC also significantly improved on two different sets of time points from 0.694 (original cine) to 0.862 (corresponding MC cine) and 0.723 to 0.886. TIC analysis displayed a significant decrease in RMSE (p = 0.018) and a significant increase in R2 goodness-of-fit (p = 0.029) for the patient cohort.

Published
2020

3. Stochastic dynamics of intermittent pore‐scale particle motion in three‐dimensional porous media: Experiments and theory

Author

Morales, VL, Dentz, M, Willmann, M, and Holzner, M

Subjects
anomalous transport, non-Fickian, velocity process, continuous time random walk, particle tracking, intermittent particle velocity, Meteorology & Atmospheric Sciences
Abstract

We study the evolution of velocity in time, which fundamentally controls the way dissolved substances are transported and spread in porous media. Experiments are conducted that use tracer particles to track the motion of substances in water, as it flows through transparent, 3-D synthetic sandstones. Particle velocities along streamlines are found to be intermittent and strongly correlated, while their probability density functions are lognormal and nonstationary. We demonstrate that these particle velocity characteristics can be explained and modeled as a continuous time random walk that is both Markovian and mean reverting toward the stationary state. Our model accurately captures the fine-scale velocity fluctuations observed in each tested sandstone, as well as their respective dispersion regime progression from initially ballistic, to superdiffusive, and finally Fickian. Model parameterization is based on the correlation length and mean and standard deviation of the velocity distribution, thus linking pore-scale attributes with macroscale transport behavior for both short and long time scales.

Published
2017

5. Intermittent Lagrangian velocities and accelerations in three-dimensional porous medium flow

Author

Holzner, M, Morales, VL, Willmann, M, and Dentz, M

Subjects
Engineering, Mathematical Sciences, Physical Sciences, 2-Propanol, Fluorocarbon Polymers, Hydrodynamics, Models, Theoretical, Porosity, Tomography, X-Ray Computed, Water, Fluids & Plasmas
Abstract

Intermittency of Lagrangian velocity and acceleration is a key to understanding transport in complex systems ranging from fluid turbulence to flow in porous media. High-resolution optical particle tracking in a three-dimensional (3D) porous medium provides detailed 3D information on Lagrangian velocities and accelerations. We find sharp transitions close to pore throats, and low flow variability in the pore bodies, which gives rise to stretched exponential Lagrangian velocity and acceleration distributions characterized by a sharp peak at low velocity, superlinear evolution of particle dispersion, and double-peak behavior in the propagators. The velocity distribution is quantified in terms of pore geometry and flow connectivity, which forms the basis for a continuous-time random-walk model that sheds light on the observed Lagrangian flow and transport behaviors.

Published
2015

9. Cu-64 as a tool in Wilson‘s disease research

Author

Willmann, M., additional, Al-Bazaz, S., additional, Korkmaz, Z., additional, Schaaf, L., additional, Kabiri, Y., additional, Zibert, A., additional, DiSpirito, A. A., additional, Semrau, J., additional, Zischka, H., additional, Plettenburg, O., additional, Bengel, F. M., additional, and Ross, T. L., additional

Published
2023
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14. Proposed Diagnostic Criteria and Classification of Canine Mast Cell Neoplasms: A Consensus Proposal

Author

Willmann M., Yuzbasiyan-Gurkan V., Marconato L., Dacasto M., Hadzijusufovic E., Hermine O., Sadovnik I., Gamperl S., Schneeweiss-Gleixner M., Gleixner K. V., Bohm T., Peter B., Eisenwort G., Moriggl R., Li Z., Jawhar M., Sotlar K., Jensen-Jarolim E., Sexl V., Horny H. -P., Galli S. J., Arock M., Vail D. M., Kiupel M., Valent P., Willmann M., Yuzbasiyan-Gurkan V., Marconato L., Dacasto M., Hadzijusufovic E., Hermine O., Sadovnik I., Gamperl S., Schneeweiss-Gleixner M., Gleixner K.V., Bohm T., Peter B., Eisenwort G., Moriggl R., Li Z., Jawhar M., Sotlar K., Jensen-Jarolim E., Sexl V., Horny H.-P., Galli S.J., Arock M., Vail D.M., Kiupel M., and Valent P.

Subjects
KIT mutations, canine mast cell neoplasm, classification, grading, staging, targeted therapy, treatment algorithms, KIT mutation, Veterinary Science, Review
Abstract

Mast cell neoplasms are one of the most frequently diagnosed malignancies in dogs. The clinical picture, course, and prognosis vary substantially among patients, depending on the anatomic site, grade and stage of the disease. The most frequently involved organ is the skin, followed by hematopoietic organs (lymph nodes, spleen, liver, and bone marrow) and mucosal sites of the oral cavity and the gastrointestinal tract. In cutaneous mast cell tumors, several grading and staging systems have been introduced. However, no comprehensive classification and no widely accepted diagnostic criteria have been proposed to date. To address these open issues and points we organized a Working Conference on canine mast cell neoplasms in Vienna in 2019. The outcomes of this meeting are summarized in this article. The proposed classification includes cutaneous mast cell tumors and their sub-variants defined by grading- and staging results, mucosal mast cell tumors, extracutaneous/extramucosal mast cell tumors without skin involvement, and mast cell leukemia (MCL). For each of these entities, diagnostic criteria are proposed. Moreover, we have refined grading and staging criteria for mast cell neoplasms in dogs based on consensus discussion. The criteria and classification proposed in this article should greatly facilitate diagnostic evaluation and prognostication in dogs with mast cell neoplasms and should thereby support management of these patients in daily practice and the conduct of clinical trials.

Published
2021

18. Increased regional ventilation as early imaging marker for future disease progression of interstitial lung disease: a feasibility study

Author

Scharm, S.C., Schaefer-Prokop, C.M., Willmann, M., Vogel-Claussen, J., Knudsen, L., Jonigk, D., Fuge, J., Welte, T., Wacker, F., Prasse, A., Shin, H.O., Scharm, S.C., Schaefer-Prokop, C.M., Willmann, M., Vogel-Claussen, J., Knudsen, L., Jonigk, D., Fuge, J., Welte, T., Wacker, F., Prasse, A., and Shin, H.O.

Abstract

Contains fulltext : 283324.pdf (Publisher’s version ) (Open Access), OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and a highly variable course. Pathologically increased ventilation-accessible by functional CT-is discussed as a potential predecessor of lung fibrosis. The purpose of this feasibility study was to investigate whether increased regional ventilation at baseline CT and morphological changes in the follow-up CT suggestive for fibrosis indeed occur in spatial correspondence. METHODS: In this retrospective study, CT scans were performed at two time points between September 2016 and November 2020. Baseline ventilation was divided into four categories ranging from low, normal to moderately, and severely increased (C1-C4). Correlation between baseline ventilation and volume and density change at follow-up was investigated in corresponding voxels. The significance of the difference of density and volume change per ventilation category was assessed using paired t-tests with a significance level of p

Published
2022

23. Needs for an Integration of Specific Data Sources and Items - First Insights of a National Survey Within the German Center for Infection Research

Author

Jakob, C.E.M., Stecher, M., Fuhrmann, S., Wingen-Heimann, S., Heinen, S., Anton, G., Behnke, M., Behrends, U., Boeker, M., Castell, S., Demski, H., Diefenbach, M., Falgenhauer, J.C., Fritzenwanker, M., Gastmeier, P., Gerhard, M., Glöckner, S., Golubovic, M., Gunsenheimer Bartmeyer, B., Ingenerf, J., Kaiser, R., Körner, M.L., Loag, W., McHardy, A.C., Molitor, E., Nübel, U., Pritsch, M., Ramharter, M., Rieg, S.R., Rupp, J., Schindler, D., Schwudke, D., Spinner, C., Stottmeier, B., Vehreschild, M., Willmann, M., Vehreschild, J.J., and BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.

Subjects
minimum data requirement, Germany, Surveys and Questionnaires, Humans, Information Storage and Retrieval, Data integration, survey, Data Integration, Infectious Diseases, Minimum Data Requirement, Survey, infectious diseases, Communicable Diseases, Hospitals
Abstract

State-subsidized programs develop medical data integration centers in Germany. To get infection disease (ID) researchers involved in the process of data sharing, common interests and minimum data requirements were prioritized. In 06/2019 we have initiated the German Infectious Disease Data Exchange (iDEx) project. We have developed and performed an online survey to determine prioritization of requests for data integration and exchange in ID research. The survey was designed with three sub-surveys, including a ranking of 15 data categories and 184 specific data items and a query of available 51 data collecting systems. A total of 84 researchers from 17 fields of ID research participated in the survey (predominant research fields: gastrointestinal infections n=11, healthcare-associated and antibiotic-resistant infections n=10, hepatitis n=10). 48% (40/84) of participants had experience as medical doctor. The three top ranked data categories were microbiology and parasitology, experimental data, and medication (53%, 52%, and 47% of maximal points, respectively). The most relevant data items for these categories were bloodstream infections, availability of biomaterial, and medication (88%, 87%, and 94% of maximal points, respectively). The ranking of requests of data integration and exchange is diverse and depends on the chosen measure. However, there is need to promote discipline-related digitalization and data exchange.

Published
2021

26. Transport upscaling in heterogeneous aquifers: What physical parameters control memory functions?

Author

Willmann, M., Carrera, Jesus, and Sánchez-Vila, Xavier

Subjects
Engineering, Manufacturing, Engineering, Mechanical, Engineering, Civil, Engineering, Industrial, Engineering, Multidisciplinary, Engineering, Ocean, Computer Science, Software Engineering, Engineering, Aerospace, Engineering, Biomedical, Engineering, Marine
Abstract

Power law tailing is often observed in the breakthrough curves (BTCs) of tracer tests. Tailing is attributed to heterogeneity of aquifer properties and cannot be properly modeled by means of the homogeneous advection‐dispersion equation. Mass transfer models (e.g., continuous time random walk method, multirate mass transfer, or fractional‐order advection‐dispersion equations) using memory have been widely applied for reproducing observed tails. The relationship between memory parameters obtained from BTC fitting and the parameters characterizing the heterogeneity of hydraulic properties is still unclear. Here we investigate the conditions under which heterogeneity produces the type of tailing observed in the field and how memory functions are influenced by measurable heterogeneity parameters (e.g., variance, variogram, or integral scale of the underlying transmissivity field). We find that the slope of a BTC in a log‐log plot is mainly influenced by the connectivity of the underlying permeability field but is insensitive to its variance. The slope BTC reaches asymptotically 2 as connectivity increases. We conclude that an appropriate choice of the memory function allows reproducing the spreading caused by hydraulic heterogeneity but not necessarily the rate of mixing.

Published
2020

28. Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia

Author

Blatt, K, Menzl, I, Eisenwort, G, Cerny-Reiterer, S, Herrmann, H, Herndlhofer, S, Stefanzl, G, Sadovnik, I, Berger, D, Keller, A, Hauswirth, A, Hoermann, G, Willmann, M, Rülicke, T, Sill, H, Sperr, WR, Mannhalter, C, Melo, JV, Jäger, U, Sexl, V, Valent, P, and Imperial College Trust

Subjects
Original article, GO, gemtuzumab-ozogamicin, NSG, NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ, Antigens, CD34, PB, peripheral blood, TKI, tyrosine kinase inhibitor, lcsh:RC254-282, Cell Line, OS, overall survival, Mice, LSC, leukemic stem cell, CML, chronic myeloid leukemia, Mice, Inbred NOD, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Biomarkers, Tumor, Animals, Humans, Oncology & Carcinogenesis, Ph, Philadelphia chromosome, Gene Expression Regulation, Leukemic, Stem Cells, 1103 Clinical Sciences, MNC, mononuclear cell, ALL, acute lymphoblastic leukemia, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ADP-ribosyl Cyclase 1, Leukemia, Myeloid, Acute, BM, bone marrow, Neoplastic Stem Cells, Female, SCT, stem cell transplantation
Abstract

Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+/CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested. Moreover, in various subgroups of patients, LSCs also displayed CD20 (MS4A1) (10/41 = 24%), CD22 (12/20 = 60%), CD33 (Siglec-3) (20/48 = 42%), CD52 (CAMPATH-1) (17/40 = 43%), IL-1RAP (13/29 = 45%), and/or CD135 (FLT3) (4/20 = 20%). CD25 (IL-2RA) and CD26 (DPPIV) were expressed on LSCs in Ph+ ALL exhibiting BCR/ABL1p210, whereas in Ph+ ALL with BCR/ABL1p190, LSCs variably expressed CD25 but did not express CD26. In Ph- ALL, CD34+/CD38- LSCs expressed IL-1RAP in 6/18 patients (33%), but did not express CD25 or CD26. Normal stem cells stained negative for CD25, CD26 and IL-1RAP, and expressed only low amounts of CD52. In xenotransplantation experiments, CD34+/CD38- and CD34+/CD38+ cells engrafted NSG mice after 12-20 weeks, and targeting with antibodies against CD33 and CD52 resulted in reduced engraftment. Together, LSCs in Ph+ and Ph- ALL display unique marker- and target expression profiles. In Ph+ ALL with BCR/ABL1p210, the LSC-phenotype closely resembles the marker-profile of CD34+/CD38- LSCs in chronic myeloid leukemia, confirming the close biologic relationship of these neoplasms. Targeting of LSCs with specific antibodies or related immunotherapies may facilitate LSC eradication in ALL.

Published
2018

29. High admission prevalence of fluoroquinolone resistance in third-generation cephalosporin-resistant Enterobacteriaceae in German university hospitals

Author

Rohde, Anna M, Wiese-Posselt, Miriam, Zweigner, Janine, Schwab, Frank, Mischnik, Alexander, Seifert, Harald, Gastmeier, Petra, Kern, Winfried V, DZIF-ATHOS Study Group Armean, S, Behnke, M, Busch, D, Feihl, S, Först, G, Foschi, F, Gillis, M, Hamprecht, A, Hansen, D, Häcker, G, Heim, M, Hug, M, Kaier, K, Knobloch, J, Kola, A, Küpper, Mf, Langebartels, G, Liekweg, A, Lipp, Hp, Nordmann, M, Obermann, B, Peña-Diaz, La, Peter, S, Querbach, C, Rupp, J, Schneider, C, Schröder, C, Schröder, W, Spohn, K, Steib-Bauert, M, Tacconelli, E, Vehreschild, Jj, Vor dem Esche, U, and Willmann, M

Subjects
Male, 0301 basic medicine, Klebsiella, Cephalosporin, Rate ratio, Hospitals, University, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Germany, Prevalence, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Cross Infection, biology, Enterobacteriaceae Infections, Middle Aged, University hospital, Enterobacteriaceae, Anti-Bacterial Agents, Hospitalization, Ciprofloxacin, Infectious Diseases, Urinary Tract Infections, Female, Fluoroquinolones, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Microbial Sensitivity Tests, Pivmecillinam, 03 medical and health sciences, Fosfomycin, Internal medicine, Escherichia coli, medicine, Humans, Risk factor, Aged, Pharmacology, business.industry, biology.organism_classification, Fluoroquinolone resistance, Cephalosporins, business, Fosfomycin, Urinary Tract Infections, Pivmecillinam
Abstract

Objectives: Fluoroquinolone resistance (FQR) in third-generation cephalosporin-resistant Enterobacteriaceae 3GCRE) presents serious limitations to antibiotic therapy. The aim of this study was to investigate whether the FQR proportion among 3GCRE differs between community-acquired (CA) and hospital-acquired (HA) isolates. Methods: In a prospective observational study covering 2014 and 2015, we monitored the occurrence of 3GCRE in adult hospitalized patients in six German university hospitals. 3GCRE clinical isolates were subdivided into CA and HA. Multivariable analysis identified factors associated with in vitro non-susceptibility to ciprofloxacin. Results: The dataset included 5721 3GCRE isolates of which 52.9% were HA and 52.7% exhibited FQR. Interestingly, the FQR proportion was higher in CA 3GCRE than in HA 3GCRE (overall, 60.1% versus 46.2%, respectively, P

Published
2018
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41. Prediction of the three-dimensional reacting two-phase flow within a jet-stabilized combustor

Author

Kurreck, M., Willmann, M., and Wittig, S.

Subjects
Combustion chambers -- Analysis, Numerical calculations -- Analysis, Engineering and manufacturing industries, Science and technology
Abstract

Numerical calculations of the two-phase flow in an experimentally well-investigated research combustor are presented. The comparison between measurements and calculations demonstrates the capabilities of the state-of-the-art Euler/Lagrange method for calculating two-phase flows, when applied to a complex reacting liquid-fueled combustor. The governing equations for gaseous and liquid phase are presented, with special emphasis on the control of the coupling process between the two phases. The relaxation method employed, together with a convergence history, shows a suitable way to achieve a fast and accurate solution for the strongly coupled two-phase flow under investigation. Furthermore, methods are presented to simulate the stochastic behavior of the atomization process caused by an air-blast atomizer. In addition to the numerical methods, experimental techniques are presented that deliver detailed information about droplet starting conditions.

Published
1998

43. Feasibility study on oil droplet flow investigations inside aero engine bearing chambers - PDPA techniques in combination with numerical approaches

Author

Glahn, A., Kurreck, M., Willmann, M., and Wittig, S.

Subjects
Aircraft engines -- Evaluation, Roller bearings -- Evaluation, Fluid dynamics -- Analysis, Engineering and manufacturing industries, Science and technology
Abstract

The present paper deals with oil droplet flow phenomena in aero engine bearing chambers. An experimental investigation of droplet sizes and velocities utilizing a Phase Doppler Particle Analyzer (PDPA) has been performed for the first time in bearing chamber atmospheres under real engine conditions. Influences of high rotational speeds are discussed for individual droplet size classes. Although this is an important contribution to a better understanding of the droplet flow impact on secondary air/oil system performance, an analysis of the droplet flow behavior requires an incorporation of numerical methods because detailed measurements as performed here suffer from both strong spatial limitations with respect to the optical accessibility in real engine applications and constraints due to the extremely time-consuming nature of an experimental flow field analysis. Therefore, further analysis is based on numerical methods. Droplets characterized within the experiments are exposed to the flow field of the gaseous phase predicted by use of our well-known CFD code EPOS. The droplet trajectories and velocities are calculated within a Lagrangian frame of reference by forward numerical integration of the particle momentum equation. This paper has been initiated rather to show a successful method of bearing chamber droplet flow analysis by a combination of droplet sizing techniques and numerical approaches than to present field values as a function of all operating parameters. However, a first insight into the complex droplet flow phenomena is given and specific problems in bearing chamber heat transfer are related to the droplet flow.

Published
1996

46. Whole-genome sequencing enabling the detection of a colistin-resistant hypermutating Citrobacter werkmanii strain harbouring a novel metallo-β-lactamase VIM-48

Author

Peter, S., primary, Bezdan, D., additional, Oberhettinger, P., additional, Vogel, W., additional, Dörfel, D., additional, Dick, J., additional, Marschal, M., additional, Liese, J., additional, Weidenmaier, C., additional, Autenrieth, I., additional, Ossowski, S., additional, and Willmann, M., additional

Published
2018
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49. IL-4 downregulates expression of the target receptor CD30 in neoplastic canine mast cells

Author

Bauer, K., Hadzijusufovic, E., Cerny-Reiterer, S., Hoermann, G., Reifinger, M., Pirker, A., Valent, P., and Willmann, M.

Subjects
Brentuximab Vedotin, Male, Immunoconjugates, Pyridines, Down-Regulation, Ki-1 Antigen, Antineoplastic Agents, Apoptosis, Drug Synergism, Staurosporine, Article, Thiazoles, Dogs, Piperidines, Cell Line, Tumor, Benzamides, Animals, Cytokines, Female, Dog Diseases, Interleukin-4, Mastocytosis
Abstract

CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this 'comparative oncology' study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC.

Published
2016

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