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1.
J Phys Chem Lett ; 10(20): 6097-6104, 2019 Oct 17.
Article in English | MEDLINE | ID: mdl-31533434

ABSTRACT

One major factor limiting the efficiency in organic solar cells (OSCs) is the low open-circuit voltage (Voc). Existing theoretical studies link the Voc with the charge transfer (CT) state and nonradiative recombination. However, also morphology and energetic disorder can have a strong impact on the Voc within realistic bulk-heterojunction OSCs. In this work, we present a kinetic Monte Carlo study on the role of the energetic disorder on the maximum Voc. We compute the quasi-Fermi level splitting for different energetic disorder and analyze the impact of the energetic disorder at the donor-acceptor interface as well as correlations in the site energies on the Voc. Our results show that the interface strongly controls the maximum Voc. For a higher interface disorder, charge densities and nongeminate recombination increase and the Voc is reduced. Furthermore, the correlated morphologies show an increase in the maximum Voc and a reduced impact of the energetic disorder.

2.
J Thromb Haemost ; 16(5): 946-959, 2018 05.
Article in English | MEDLINE | ID: mdl-29512284

ABSTRACT

Essentials Heat shock protein 47 (HSP47), a collagen specific chaperone is present on the platelet surface. Collagen mediated platelet function was reduced following blockade or deletion of HSP47. GPVI receptor regulated signalling was reduced in HSP47 deficient platelets. Platelet HSP47 tethers to exposed collagen thus modulating thrombosis and hemostasis. SUMMARY: Objective Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering hemostasis and thrombosis, in this study we sought to characterize the role of HSP47 in these cells. Methods and Results The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI-collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions, was also decreased following the inhibition or deletion of HSP47, in the presence or absence of eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand factor was unaltered following HSP47 inhibition. Laser-induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47-deficient mice or following inhibition of HSP47. Conclusions Our study demonstrates the presence of HSP47 on the platelet surface, where it interacts with collagen, stabilizes platelet adhesion and increases collagen-mediated signalling and therefore thrombus formation and hemostasis.


Subject(s)
Blood Platelets/metabolism , Carrier Proteins/blood , Collagen/blood , HSP70 Heat-Shock Proteins/blood , Hemostasis , Platelet Activation , Thrombosis/blood , Animals , Blood Platelets/drug effects , Calcium Signaling , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/genetics , Disease Models, Animal , HSP70 Heat-Shock Proteins/antagonists & inhibitors , HSP70 Heat-Shock Proteins/deficiency , HSP70 Heat-Shock Proteins/genetics , Hemostasis/drug effects , Humans , Mice, Inbred C57BL , Mice, Knockout , Mitochondrial Proteins , Platelet Activation/drug effects , Platelet Adhesiveness , Platelet Aggregation Inhibitors/pharmacology , Platelet Membrane Glycoproteins/metabolism , Protein Binding , Thrombosis/genetics , Thrombosis/prevention & control
3.
Eur Radiol ; 25(6): 1793-800, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25577524

ABSTRACT

OBJECTIVES: To evaluate the accuracy of MRI of the breast (DCE-MRI) in a stand-alone setting with extended indications. MATERIALS AND METHODS: According to the inclusion criteria, breast specialists were invited to refer patients to our institution for DCE-MRI. Depending on the MR findings, patients received either a follow-up or biopsy. Between 04/2006 and 12/2011 a consecutive total of 1,488 women were prospectively examined. RESULTS: Of 1,488 included patients, 393 patients were lost to follow-up, 1,095 patients were evaluated. 124 patients were diagnosed with malignancy by DCE-MRI (76 TP, 48 FP, 971 TN, 0 FN cases). Positive cases were confirmed by histology, negative cases by MR follow-ups or patient questionnaires over the next 5 years in 1,737 cases (sensitivity 100 %; specificity 95.2 %; PPV 61.3 %; NPV 100 %; accuracy 95.5 %). For invasive cancers only (DCIS excluded), the results were 63 TP; 27 FP; 971 TP and 0 FN (sensitivity 100 %; specificity 97.2 %; PPV 70 %; NPV 100 %; accuracy 97.5 %). CONCLUSION: The DCE-MRI indications tested imply that negative results in DCE-MRI reliably exclude cancer. The results were achieved in a stand-alone setting (single modality diagnosis). However, these results are strongly dependent on reader experience and adequate technical standards as prerequisites for optimal diagnoses. KEY POINTS: • DCE-MRI of the breast has a high accuracy in finding breast cancer. • The set of indications for DCE-MRI of the breast is still very limited. • DCE-MRI can achieve a high accuracy in a 'screening-like' setting. • Accuracy of breast DCE-MRI is strongly dependent on technique and reader experience. • A negative DCE-MRI effectively excludes cancer.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Adult , Biopsy , Breast/pathology , Contrast Media , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Prospective Studies , Sensitivity and Specificity
4.
J Thromb Haemost ; 12(8): 1342-52, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24888521

ABSTRACT

BACKGROUND: Integrin-linked kinase (ILK) and its associated complex of proteins are involved in many cellular activation processes, including cell adhesion and integrin signaling. We have previously demonstrated that mice with induced platelet ILK deficiency show reduced platelet activation and aggregation, but only a minor bleeding defect. Here, we explore this apparent disparity between the cellular and hemostatic phenotypes. METHODS: The impact of ILK inhibition on integrin αII b ß3 activation and degranulation was assessed with the ILK-specific inhibitor QLT0267, and a conditional ILK-deficient mouse model was used to assess the impact of ILK deficiency on in vivo platelet aggregation and thrombus formation. RESULTS: Inhibition of ILK reduced the rate of both fibrinogen binding and α-granule secretion, but was accompanied by only a moderate reduction in the maximum extent of platelet activation or aggregation in vitro. The reduction in the rate of fibrinogen binding occurred prior to degranulation or translocation of αII b ß3 to the platelet surface. The change in the rate of platelet activation in the absence of functional ILK led to a reduction in platelet aggregation in vivo, but did not change the size of thrombi formed following laser injury of the cremaster arteriole wall in ILK-deficient mice. It did, however, result in a marked decrease in the stability of thrombi formed in ILK-deficient mice. CONCLUSION: Taken together, the findings of this study indicate that, although ILK is not essential for platelet activation, it plays a critical role in facilitating rapid platelet activation, which is essential for stable thrombus formation.


Subject(s)
Platelet Activation , Protein Serine-Threonine Kinases/metabolism , Thrombosis/enzymology , Animals , Flow Cytometry , Mice , Mice, Transgenic , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
5.
J Phys Chem B ; 118(2): 597-607, 2014 Jan 16.
Article in English | MEDLINE | ID: mdl-24377364

ABSTRACT

Self-assembled monolayers of charged polymers are an integral component of many state-of-the-art nanobiosensors. Electrical interactions between charged surfaces and charged biomolecules, adopting the roles of linkers or capture molecules, are not only crucial to the sensor performance but may also be exploited for novel sensing concepts based on electrically actuated interfaces. Here we introduce an analytical model describing the behavior of double-stranded DNA and proteins tethered to externally biased microelectrodes. Continuum electrostatic Poisson-Boltzmann models and the drift-diffusion (Smoluchowski) equation are used to calculate the steady state as well as the dynamic behavior of oligonucleotide rods in DC and AC electric fields. The model predicts the oligonucleotide orientation on the surface and calculates how the increased hydrodynamic drag caused by a protein bound to the DNA's distal end affects the molecular dynamics of the DNA-protein complex. The results of the model are compared to experiments with electrically switchable DNA layers, and very good agreement between theory and experiment is found. The hydrodynamic diameter of the bound protein can be analyzed from experimental data of the slowed motion of the DNA-protein conjugate with angstrom precision.


Subject(s)
DNA/chemistry , Molecular Dynamics Simulation , Proteins/chemistry , DNA/metabolism , Diffusion , Electricity , Entropy , Microelectrodes , Models, Chemical , Proteins/metabolism , Static Electricity , Surface Properties
6.
Cell Signal ; 26(3): 502-11, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24308967

ABSTRACT

Ca(2+) elevation is essential to platelet activation. STIM1 senses Ca(2+) in the endoplasmic reticulum and activates Orai channels allowing store-operated Ca(2+) entry (SOCE). STIM1 has also been reported to be present in the plasma membrane (PM) with its N-terminal region exposed to the outside medium but its role is not fully understood. We have examined the effects of the antibody GOK/STIM1, which recognises the N-terminal region of STIM1, on SOCE, agonist-stimulated Ca(2+) entry, surface exposure, in vitro thrombus formation and aggregation in human platelets. We also determined novel binding partners of STIM1 using proteomics. The dialysed GOK/STIM1 antibody failed to reduced thapsigargin- and agonist-mediated Ca(2+) entry in Fura2-labelled cells. Using flow cytometry we detect a portion of STIM1 to be surface-exposed. The dialysed GOK/STIM1 antibody reduced thrombus formation by whole blood on collagen-coated capillaries under flow and platelet aggregation induced by collagen. In immunoprecipitation experiments followed by proteomic analysis, STIM1 was found to extract a number of proteins including myosin, DOCK10, thrombospondin-1 and actin. These studies suggest that PM STIM1 may facilitate platelet activation by collagen through novel interactions at the plasma membrane while the essential Ca(2+)-sensing role of STIM1 is served by the protein in the ER.


Subject(s)
Collagen/metabolism , Endoplasmic Reticulum/metabolism , Membrane Proteins/immunology , Neoplasm Proteins/immunology , Platelet Activation/immunology , Platelet Aggregation/immunology , Acetamides/pharmacology , Actins/metabolism , Anilides/pharmacology , Antibodies/immunology , Antibodies/pharmacology , Blood Platelets , Calcium , Calcium Signaling/drug effects , Calcium Signaling/immunology , Enzyme Inhibitors/pharmacology , Guanine Nucleotide Exchange Factors/metabolism , Humans , Ion Channels/drug effects , Isoquinolines/pharmacology , Myosins/metabolism , Platelet Activation/drug effects , Protein Binding/immunology , Stromal Interaction Molecule 1 , Thapsigargin/pharmacology , Thiadiazoles/pharmacology , Thrombosis/immunology , Thrombospondin 1/metabolism
7.
Cell Death Differ ; 20(11): 1510-20, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23892366

ABSTRACT

Apaf1 is an evolutionarily conserved component of the apoptosome. In mammals, the apoptosome assembles when cytochrome c is released from mitochondria, binding Apaf1 in an ATP-dependent manner and activating caspase 9 to execute apoptosis. Here we identify and characterize a novel mouse mutant, yautja, and find it results from a leucine-to-proline substitution in the winged-helix domain of Apaf1. We show that this allele of Apaf1 is unique, as the yautja mutant Apaf1 protein is stable, yet does not possess apoptotic function in cell culture or in vivo assays. Mutant embryos die perinatally with defects in craniofacial and nervous system development, as well as reduced levels of apoptosis. We further investigated the defects in craniofacial development in the yautja mutation and found altered Sonic hedgehog (Shh) signaling between the prechordal plate and the frontonasal ectoderm, leading to increased mesenchymal proliferation in the face and delayed or absent ossification of the skull base. Taken together, our data highlight the time-sensitive link between Shh signaling and the regulation of apoptosis function in craniofacial development to sculpt the face. We propose that decreased apoptosis in the developing nervous system allows Shh-producing cells to persist and direct a lateral outgrowth of the upper jaw, resulting in the craniofacial defects we see. Finally, the novel yautja Apaf1 allele offers the first in vivo understanding of a stable Apaf1 protein that lacks a function, which should make a useful tool with which to explore the regulation of programmed cell death in mammals.


Subject(s)
Apoptosis/physiology , Apoptotic Protease-Activating Factor 1/metabolism , Craniofacial Abnormalities/embryology , Craniofacial Abnormalities/metabolism , Hedgehog Proteins/metabolism , Animals , Embryo, Mammalian , Female , Genotype , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Pregnancy , Signal Transduction
8.
Med Image Anal ; 17(2): 209-18, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23265802

ABSTRACT

Due to their different physical origin, X-ray mammography and Magnetic Resonance Imaging (MRI) provide complementary diagnostic information. However, the correlation of their images is challenging due to differences in dimensionality, patient positioning and compression state of the breast. Our automated registration takes over part of the correlation task. The registration method is based on a biomechanical finite element model, which is used to simulate mammographic compression. The deformed MRI volume can be compared directly with the corresponding mammogram. The registration accuracy is determined by a number of patient-specific parameters. We optimize these parameters--e.g. breast rotation--using image similarity measures. The method was evaluated on 79 datasets from clinical routine. The mean target registration error was 13.2mm in a fully automated setting. On basis of our results, we conclude that a completely automated registration of volume images with 2D mammograms is feasible. The registration accuracy is within the clinically relevant range and thus beneficial for multimodal diagnosis.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/physiopathology , Imaging, Three-Dimensional/methods , Mammography/methods , Models, Biological , Pattern Recognition, Automated/methods , Subtraction Technique , Algorithms , Computer Simulation , Female , Finite Element Analysis , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Reproducibility of Results , Sensitivity and Specificity
9.
Rofo ; 184(7): 618-23, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22722908

ABSTRACT

PURPOSE: Accurate staging of primary breast cancer is essential for the therapeutic approach. Modern whole-body MR scanners would allow local and distant staging during a single examination. Accordingly, we designed a dedicated protocol for this purpose and prospectively evaluated the diagnostic accuracy. MATERIALS AND METHODS: 65 consecutive breast cancer patients underwent pre-therapeutic MRI (1.5 T). A bilateral breast protocol (axial: T1w/GRE dynamic contrast-enhanced, T2w/TSE; TA: 10 min) was extended to screen for distant metastasis at one stop without repositioning (coronal: T2w/HASTE, T1w/VIBE; FOV: thorax, abdomen and spine; TA: 90 sec; multichannel surface coils). The standard of reference was S3 guideline-compliant staging examinations. Global assessment regarding the presence of distant metastasis was performed independently by two experienced and blinded radiologists (five-level confidence score). Inter-rater agreement (weighted kappa) and observer scoring were analyzed (contingency tables). RESULTS: The prevalence of synchronous metastases was 7.7 % (n = 5). The protocol enabled global assessment regarding the presence of distant metastasis with high accuracy (sensitivity: 100 %; specificity: 98.3 %) and inter-rater agreement (kappa: 0.92). CONCLUSION: Applying the extended MRI protocol, accurate screening for distant metastasis was possible in combination with a dedicated breast examination.


Subject(s)
Breast Neoplasms/pathology , Carcinoma/pathology , Carcinoma/secondary , Magnetic Resonance Imaging/methods , Mass Screening/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Neoplasm Staging , Pilot Projects , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity
10.
Rofo ; 184(9): 788-94, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22618476

ABSTRACT

PURPOSE: To evaluate the diagnostic accuracy of qualitative descriptors alone and in combination for the classification of focal liver lesions (FLLs) suspicious for metastasis in gadolinium-EOB-DTPA-enhanced liver MR imaging. MATERIALS AND METHODS: Consecutive patients with clinically suspected liver metastases were eligible for this retrospective investigation. 50 patients met the inclusion criteria. All underwent Gd-EOB-DTPA-enhanced liver MRI (T2w, chemical shift T1w, dynamic T1w). Primary liver malignancies or treated lesions were excluded. All investigations were read by two blinded observers (O1, O2). Both independently identified the presence of lesions and evaluated predefined qualitative lesion descriptors (signal intensities, enhancement pattern and morphology). A reference standard was determined under consideration of all clinical and follow-up information. Statistical analysis besides contingency tables (chi square, kappa statistics) included descriptor combinations using classification trees (CHAID methodology) as well as ROC analysis. RESULTS: In 38 patients, 120 FLLs (52 benign, 68 malignant) were present. 115 (48 benign, 67 malignant) were identified by the observers. The enhancement pattern, relative SI upon T2w and late enhanced T1w images contributed significantly to the differentiation of FLLs. The overall classification accuracy was 91.3 % (O1) and 88.7 % (O2), kappa = 0.902. CONCLUSION: The combination of qualitative lesion descriptors proposed in this work revealed high diagnostic accuracy and interobserver agreement in the differentiation of focal liver lesions suspicious for metastases using Gd-EOB-DTPA-enhanced liver MRI.


Subject(s)
Algorithms , Gadolinium DTPA , Image Interpretation, Computer-Assisted/methods , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Magnetic Resonance Imaging/methods , Pattern Recognition, Automated/methods , Adult , Aged , Contrast Media , Decision Support Techniques , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
11.
Herz ; 37(5): 573-8, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22430283

ABSTRACT

A 54-year-old female patient presented with a progressive and deteriorating dyspnea at the slightest exertion in particular during the past few days before presentation. Transthoracic echocardiography revealed a large space-occupying lesion in the right atrium extending into the inferior vena cava (IVC). Abdominal magnetic resonance aortography showed an elongated space-occupying lesion in the IVC with a significant portion of the tumor and almost completely filling the right atrium accompanied by an infiltration of the hepatic and renal veins. A pronounced tumor infiltration of the IVC at the level of the liver was confirmed intraoperatively and immunohistochemical analysis showed a moderate to poorly differentiated leiomyosarcoma. The extended tumor was successfully removed by a complex operation of the thorax and abdomen but the procedure was accompanied by severe bleeding. A few hours following the procedure the patient died due to a further episode of irreversible intra-abdominal hemorrhage.


Subject(s)
Heart Neoplasms/surgery , Leiomyosarcoma/surgery , Fatal Outcome , Female , Heart Atria/surgery , Humans , Middle Aged , Neoplasm Invasiveness , Vena Cava, Inferior/surgery
12.
Eur J Radiol ; 81(7): 1500-3, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21481556

ABSTRACT

OBJECTIVE: Perifocal edema, defined as high T2w signal intensity around an enhancing lesion has been described as a specific feature of malignancy. In clinical MR-mammography (MRM), both fatsat and non-fatsat T2w sequences are available. However, there is no consensus on which technique should be used for edema assessment. Consequently, this investigation was performed to compare two commonly used pulse sequences for edema assessment in MRM. MATERIALS AND METHODS: 321 consecutive patients from a 22 month period were included in this investigation. Further selection criteria were histopathological verification of enhancing lesions and absence of presurgical chemotherapy or biopsy, resulting in 108 malignant and 107 benign lesions. All underwent MRM according to international guidelines including a non-fatsat T2w-TSE sequence (TR/TE: 8900/207 ms) and a short tau inversion recovery fatsat sequence (STIR, TR/TE: 8420/70 ms). All images were acquired in the same orientation (axial) and slice thickness. Two experienced radiologists in consensus rated presence of perifocal edema according to an ordinal scale: 0 = not present, 1 = little, 2 = intermediate, and 3 = distinct. Data analysis was performed using crosstabs and Visual Grading Characteristics (VGC) analysis. RESULTS: Overall sensitivity/specificity was calculated with 53.7%/94.4% (T2w-TSE) and 52.8%/95.3% (STIR). VGC revealed an area under the VGC curve of 0.502 (standard error 0.026), P = 0.814. CONCLUSION: Perifocal edema is a specific feature of malignancy with moderate sensitivity. VGC analysis did not reveal significant differences between both pulse sequences analysed. Consequently, both T2w-TSE and STIR images are suitable for assessment of perifocal edema.


Subject(s)
Breast Neoplasms/diagnosis , Edema/diagnosis , Magnetic Resonance Imaging/methods , Mammography , Area Under Curve , Breast Neoplasms/pathology , Contrast Media , Female , Gadolinium DTPA , Humans , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity
13.
Dtsch Med Wochenschr ; 136(41): 2094-9, 2011 Oct.
Article in German | MEDLINE | ID: mdl-21971885

ABSTRACT

Actually myocardial perfusion scintigraphy (MIP) is best evaluated imaging modality in patients with coronary artery disease. It detects flow-limiting coronary artery disease with high sensitivity and specificity, enables recognition of the grade of severity and extensiveness of myocardial ischemia, and furthermore enables assessment of future cardiac events independently of clinical and diagnostic parameters. Due to rapid technical evolution in diagnostic tools there is need of comparison between MIP and other concurrent imaging modalities such as stress echocardiography, Cardio-CT and Cardio-MRI in patients with coronary artery disease.


Subject(s)
Coronary Disease/diagnosis , Myocardial Perfusion Imaging , Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography , Coronary Angiography , Coronary Stenosis/diagnosis , Echocardiography, Stress , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Angiography , Myocardial Infarction/diagnosis , Sensitivity and Specificity , Tomography, X-Ray Computed
14.
AJNR Am J Neuroradiol ; 32(7): 1321-7, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21511866

ABSTRACT

BACKGROUND AND PURPOSE: Cerebral hypoglycemia can result in reversible metabolic brain insults and can be associated with impaired diffusion disturbances. Our aim was to evaluate possible changes in DWI of the human brain during hyperacute short-term severe hypoglycemia. MATERIALS AND METHODS: Ten individuals scheduled for a clinical IST were examined with DWI while the test was performed. Venous blood glucose was continuously measured, and sequential DWI sequences were performed without interruption. Hypoglycemia was terminated with intravenous glucose administration when glucose levels were at ≤2.0 mmol/L. RESULTS: Blood glucose levels were lowered to a mean nadir of 1.75 ± 0.38 mmol/L. No alterations of cerebral diffusion could be observed in any individuals on DWI. CONCLUSIONS: Hyperacute short-term severe hypoglycemia does not induce visible changes in DWI of the human brain.


Subject(s)
Brain Diseases/metabolism , Brain Diseases/pathology , Diffusion Magnetic Resonance Imaging/methods , Hypoglycemia/metabolism , Hypoglycemia/pathology , Acute Disease , Adrenal Insufficiency/complications , Adrenal Insufficiency/metabolism , Adult , Blood Glucose/drug effects , Brain Diseases/etiology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Female , Glucose/administration & dosage , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Male , Middle Aged , Severity of Illness Index , Time Factors , Young Adult
15.
Rofo ; 183(9): 826-33, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21442559

ABSTRACT

PURPOSE: Tumor grading (TG) is one of the most widely used prognostic factors in the case of breast cancer. This study aims to identify the potential of magnetic resonance mammography (MRM) to non-invasively assess TG. MATERIALS AND METHODS: 399 invasive breast cancers were included (IRB approval; standardized clinical MRM protocols). All breast cancers were prospectively evaluated by two experienced (> 500 MRM) and blinded radiologists in consensus. In every cancer a set of 18 previously published MRM descriptors was assessed. These were assessed by univariate and multivariate analysis to identify the potential of MRM to predict TG (X2 statistics; binary logistic regression; area under the ROC curve [AUC]). RESULTS: 8 of 18 MRM descriptors were associated with TG, e. g. internal structure, edema (p < 0.001), as well as skin thickening and destruction of the nipple line (p < 0.05). MRM was feasible to predict TG by multivariate analysis (p < 0.001). The highest potential could be identified to predict well differentiated breast cancers with good prognosis (AUC = 0.930). CONCLUSION: MR mammography was able to non-invasively assess tumor grading in a standard protocol. Since tumor grading is a surrogate for overall survival, these results provide further evidence to the clinical application of MR mammography as a noninvasive prognostic tool.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Mammography/methods , Adult , Aged , Aged, 80 and over , Breast/pathology , Breast Neoplasms/classification , Breast Neoplasms/surgery , Contrast Media/administration & dosage , Female , Gadolinium DTPA , Humans , Mastectomy , Mastectomy, Segmental , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prospective Studies , Reference Standards , Sensitivity and Specificity
16.
AJNR Am J Neuroradiol ; 32(3): 460-4, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21292799

ABSTRACT

BACKGROUND AND PURPOSE: Improved MR imaging at higher field strengths enables more detailed imaging of cranial nerves. The aim of this study was to assess the identifiability of the NI in the CPA and IAC by using high-resolution 3T MR imaging. MATERIALS AND METHODS: Twenty-seven healthy volunteers (13 men and 14 women; mean age, 33 years) underwent 3T MR imaging of the CPA. The section thicknesses of the CISS sequence was 0.4 mm (TR, 12.18 ms; TE, 6.09 ms) using a 12-channel head coil. Evaluation was performed by using MPR mode. Image quality and identifiability of the NI were rated independently by 2 observers according to predefined criteria on an ordinal scale. Interobserver agreement was assessed by κ statistics. RESULTS: Fifty-four NIs were evaluated. Both observers were able to identify the NI in nearly 60% of cases. It was possible to indentify at least 1 NI in 70% of all volunteers in the CPA and/or IAC. Image quality ratings showed a substantial agreement (κ = 0.65) and identifiability ratings an almost perfect (κ = 0.83) agreement. CONCLUSIONS: Careful evaluation of all nervous and vascular structures in the CPA and IAC at high-resolution 3T MR imaging allows reliable depiction of the NI.


Subject(s)
Facial Nerve/anatomy & histology , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Aged , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
17.
Rofo ; 183(5): 441-7, 2011 May.
Article in English | MEDLINE | ID: mdl-21318935

ABSTRACT

PURPOSE: Hormonal stimulation can induce background enhancement (BE) in MR mammography (MRM). This fact has been assumed to decrease the accuracy of MRM. Consequently, this report investigates: 1. The prevalence of BE in postmenopausal vs. premenopausal women in correlation to hormonal cycle phase (CP). 2. The impact of hormonal status (HS) and BE on diagnostic accuracy. MATERIALS AND METHODS: Consecutive patients over 22 months with complete HS information (week of CP or postmenopausal) were included in this prospective investigation. Exclusion criteria were any hormonal therapy, hysterectomy as well as cancer proven by biopsy. The standard of reference was histopathology. All MRM scans were acquired using the same protocol (1.5 T, dynamic T 1w GRE after 0.1 mmol/kg bw Gd-DTPA i. v.). Two radiologists rated all examinations in consensus according to BI-RADS. BE was defined as: 0 = missing, 1 = moderate, 2 = distinct. RESULTS: 224 patients (150 postmenopausal, 74 premenopausal, 45 in the second week of CP) were included in this study (83 benign and 141 malignant findings). BE was more frequent in premenopausal women (p = 0.006), but did not differ between CP (p = 0.460). Neither HS nor BE had a significant impact on the diagnostic parameters of MRM (p ≥ 0.375). However, regarding BE, the relative number of false positive (FP) findings was highest (5 / 10; 50 %) in the distinct BE group. Regarding HS, 17 % more FP findings were observed in premenopausal women examined outside the second week of CP. CONCLUSION: In premenopausal women, HS leads to increased BE of breast tissue, independent of CP. Distinct BE and less pronounced, non-optimal CP may lead to an increased number of false positive findings.


Subject(s)
Breast Neoplasms/blood , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/blood , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Intraductal, Noninfiltrating/blood , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Lobular/blood , Carcinoma, Lobular/diagnosis , Estrogens/blood , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Mammography/methods , Menstrual Cycle/blood , Postmenopause/blood , Progesterone/blood , Adult , Aged , Aged, 80 and over , Biopsy , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Lobular/pathology , Contrast Media , Female , Fibroadenoma/blood , Fibroadenoma/diagnosis , Fibroadenoma/pathology , Gadolinium DTPA , Humans , Middle Aged , Neoplasm Invasiveness , Papilloma/blood , Papilloma/diagnosis , Papilloma/pathology , Sensitivity and Specificity , Ultrasonography, Mammary , Young Adult
18.
Rofo ; 183(2): 126-35, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20830650

ABSTRACT

PURPOSE: This study was conducted to investigate the appearance of breast lesions in MR mammography (MRM) as a function of size and to identify the potential impact on diagnostic accuracy. MATERIALS AND METHODS: 936 histologically verified breast lesions (standardized MRM protocol; consecutive 12-year period at our institution, diameter 5 - 50 mm) were prospectively evaluated in consensus by two radiologists with significant MRM experience. For this purpose previously published descriptors (n = 17) were used. These were summarized as the "basic catalog and extended catalog" of descriptors (BC vs. EC). According to a cut-off of 20 mm, the database was divided into the subgroups "small" (n = 669) and "advanced" (n = 267). The diagnostic accuracy of MRM in these two subgroups was then determined using BC and EC, separately (binary logistic regression analysis; AUC analysis). RESULTS: The majority of descriptors (n = 11) showed a significantly different prevalence in correlation with size (p < 0.05). The diagnostic accuracy of MRM for "advanced" lesions (AUC = 0.969) was significantly higher (p < 0.001). This difference was significantly decreased (p < 0.001), if instead of BC (AUC = 0.865) EC was applied for the assessment of "small" lesions (AUC: 0.908 vs. 0.865). CONCLUSION: The typical appearance of breast lesions in MRM depends on lesion size. This resulted in lower diagnostic accuracy in small lesions compared to advanced findings. This difference was able to be significantly decreased by applying the catalog of extended descriptors.


Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Lobular/diagnosis , Magnetic Resonance Imaging/methods , Mammography/methods , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Breast/pathology , Breast Diseases/diagnosis , Breast Diseases/pathology , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Lobular/pathology , Contrast Media/administration & dosage , Diagnosis, Differential , Female , Gadolinium DTPA , Humans , Middle Aged , Neoplasm Staging , Sensitivity and Specificity , Tumor Burden , Young Adult
19.
Neuroscience ; 172: 547-53, 2011 Jan 13.
Article in English | MEDLINE | ID: mdl-21044659

ABSTRACT

Data on the prevalence of persistent olfactory bulb ventricles (OBV) in humans remain contradictory. The aim of this study was to investigate the hypothesis of large cystic-like OBVs filled with cerebrospinal fluid (CSF) as a frequent finding in magnetic resonance imaging (MRI). Fifty normosmic volunteers (25 men and 25 women, mean 40 years) underwent 3 Tesla MRI of the anterior skull base. Normal smell function was determined by testing of the odor threshold discrimination identification score using the Sniffin' Sticks test kit. The voxel size of the constructive interference in steady state (CISS) sequence was 0.4×0.4×0.4 mm (TR 12.18 ms, TE 6.09 ms) using a 12-channel head coil. Image quality was rated by three observers according to predefined criteria on an ordinal scale. Additionally, contrast-to-noise (CNR) and signal-to-noise (SNR) ratios were calculated. Quantitative signal intensity (SI) measurement of olfactory bulb (OB) structures and small Virchow-Robin spaces (VRS) was performed using multi planar reconstruction mode. Ninety-one OBs were eligible for evaluation. Image quality was rated as adequate in 55% and as excellent in 36% of cases. CNR and SNR calculations resulted in values of 21.59 and 19.06, respectively. Wilcoxon signed rank test revealed significant higher SI values for OB center compared to OB surface (P<0.001) and to OB base (P<0.001) but also significant lower SI values compared to small VRS (P<0.001) in 94.5%. In 5.5%, SI measurement revealed signs for CSF-filled structures in the OB. High-resolution 3 Tesla MRI did not verify the hypothesis of large cystic CSF-filled OBVs as a frequent finding although evidence is growing that the hyperintense signal in the center of OBs might be associated with interstitial or finely dispersed CSF/fluid or with tiny, histologically detectable remnants of OBVs.


Subject(s)
Cerebral Ventricles/anatomy & histology , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Olfactory Bulb/anatomy & histology , Body Patterning/physiology , Cerebral Ventricles/growth & development , Cerebrospinal Fluid/physiology , Female , Humans , Male , Neurologic Examination/methods , Olfactory Bulb/growth & development , Organogenesis/physiology , Reference Values , Smell/physiology
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