Search

Introduction Urothelial bladder cancer (UBC) with clinical suspicion of locally advanced growth or pelvic lymphogenic spread has a high risk of progression and death. Patients and methods Bladder cancer patients with locally advanced (cT3/4) tumor growth or suspected pelvic lymphogenic spread (cN+) were treated with preoperative cisplatin-containing chemotherapy and consolidative cystectomy with pelvic lymphadenectomy. We aimed to identify prognostic factors and describe the patients’ oncological outcome. Results A complete dataset including follow-up data was available for 96 patients. In a univariate analysis, we identified cN stage (cN+ vs cN-, HR 2.7, 95% CI 1.3–6.0), response to chemotherapy (HR 0.2, 95% CI 0.1–0.5), ypT stage (ypT0/is/1 vs ypT2-4, HR 3.1, 95% CI 1.4–6.8), ypN stage (ypN + vs ypN-, HR 7.9, 95% CI 3.7–17.0), resection status (HR 4.4, 95% CI HR 1.5–13.0) as significantly associated with cancer-specific survival. In a multivariate regression analysis, both cN and ypN statuses were validated as independent prognostic factors for cancer-specific survival (cN: HR 2.6, 95% CI 1.1–6.1; ypN: HR 5.5, 95% CI 2.0–15.1). Discussion Lymph node status was identified as a prognostic marker in a high-risk cohort of UBC patients treated with inductive chemotherapy and cystectomy. Establishing cN status as a prognosticator underlines the necessity to aggressively treat these patients despite reported impreciseness of imaging procedures in UCB. Patients with histologically positive lymph nodes following preoperative chemotherapy have a very poor prognosis, and thus, the need for adjuvant systemic treatment is emphasized. Conclusion Both clinically and pathologically affected lymph nodes convey a poor prognosis in bladder cancer and necessitate aggressive treatment.

Purpose Renal cysts comprise benign and malignant entities. Risk assessment profits from CT/MRI imaging using the Bosniak classification. While Bosniak-IIF, -III, and -IV cover complex cyst variants, Bosniak-IIF and -III stand out due to notorious overestimation. Contrast-enhanced ultrasound (CEUS) is promising to overcome this deficit but warrants standardization. This study addresses the benefits of a combined CEUS and CT/MRI evaluation of renal cysts. The study provides a realistic account of kidney tumor boards' intricacies in trying to validate renal cysts. Methods 247 patients were examined over 8 years. CEUS lesions were graded according to CEUS-Bosniak (IIF, III, IV). 55 lesions were resected, CEUS-Bosniak- and CT/MRI-Bosniak-classification were correlated with histopathological diagnosis. Interobserver agreement between the classifications was evaluated statistically. 105 lesions were followed by ultrasound, and change in CEUS-Bosniak-types and lesion size were documented. Results 146 patients (156 lesions) were included. CEUS classified 67 lesions as CEUS-Bosniak-IIF, 44 as CEUS-Bosniak-III, and 45 as CEUS-Bosniak-IV. Histopathology of 55 resected lesions revealed benign cysts in all CEUS-Bosniak-IIF lesions (2/2), 40% of CEUS-Bosniak-III and 8% of CEUS-Bosniak-IV, whereas malignancy was uncovered in 60% of CEUS-Bosniak-III and 92% of CEUS-Bosniak-IV. Overall, CEUS-Bosniak-types matched CT/MRI-Bosniak types in 58% (fair agreement, κ = 0.28). CEUS-Bosniak resulted in higher stages than CT/MRI-Bosniak (40%). Ultrasound follow-up of 105 lesions detected no relevant differences between CEUS-Bosniak-types concerning cysts size. 99% of lesions showed the same CEUS-Bosniak-type. Conclusion The CEUS-Bosniak classification is an essential tool in clinical practice to differentiate and monitor renal cystic lesions and empowers diagnostic work-up and patient care.

Supplemetary Tables 1-3

Purpose:Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT).Patients and Methods:Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses.Results:The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%–90%] for the INT arm and 33% (95% CI, 5%–68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood.Conclusions:Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.

Objectives To compare the visibility of anatomical structures and overall quality of the attenuation images obtained with a dark-field X-ray radiography prototype with those from a commercial radiography system. Methods Each of the 65 patients recruited for this study obtained a thorax radiograph at the prototype and a reference radiograph at the commercial system. Five radiologists independently assessed the visibility of anatomical structures, the level of motion artifacts, and the overall image quality of all attenuation images on a five-point scale, with 5 points being the highest rating. The average scores were compared between the two image types. The differences were evaluated using an area under the curve (AUC) based z-test with a significance level of p ≤ 0.05. To assess the variability among the images, the distributions of the average scores per image were compared between the systems. Results The overall image quality was rated high for both devices, 4.2 for the prototype and 4.6 for the commercial system. The rating scores varied only slightly between both image types, especially for structures relevant to lung assessment, where the images from the commercial system were graded slightly higher. The differences were statistically significant for all criteria except for the bronchial structures, the cardiophrenic recess, and the carina. Conclusions The attenuation images acquired with the prototype were assigned a high diagnostic quality despite a lower resolution and the presence of motion artifacts. Thus, the attenuation-based radiographs from the prototype can be used for diagnosis, eliminating the need for an additional conventional radiograph. Key Points • Despite a low tube voltage (70 kVp) and comparably long acquisition time, the attenuation images from the dark-field chest radiography system achieved diagnostic quality for lung assessment. • Commercial chest radiographs obtained a mean rating score regarding their diagnostic quality of 4.6 out of 5, and the grating-based images had a slightly lower mean rating score of 4.2 out of 5. • The difference in rating scores for anatomical structures relevant to lung assessment is below 5%.

Summary: Background: Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). Methods: In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)—which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. Findings: Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=–0·27, p=0·089 and visual emphysema ρ=–0·45, p=0·0028), the dark-field signal (ρ=0·62, p

Ohne intensive Nutzung von Metallen wäre die Umsetzung von aktuellen Strategien wie die Realisierung der regenerativen Energiegewinnung oder der Elektromobilität in Deutschland undenkbar. Eine gesicherte Versorgung der Industrie mit allen Primärmetallen kann durch faktische Monopolstrukturen sowie tendenziell sinkenden Erzgehalten nicht als garantiert angesehen werden. Durch eine verbesserte Kreislaufführung kann die Ressourceneffizienz erhöht und die Importabhängigkeit reduziert werden. Damit einhergehende Herausforderungen und mögliche Lösungsansätze werden thematisiert. Without the intensive use of metals, the implementation of current strategies such as the realisation of renewable energy production or electromobility in Germany would be unthinkable. A secure supply of all primary metals to industry cannot be considered guaranteed due to de facto monopoly structures and the trend towards decreasing ore contents. Improved recycling can increase resource efficiency and reduce dependence on imports. The challenges associated with this and possible solutions are discussed.

One of the biggest challenges to 3D printing is that typical desktop printers are stationary with a limited workspace. A mobile 3D-printing platform, which has omnidirectional wheels that allow for unrestricted movement along x- and y-axes, can alleviate that restriction. The research team in this project performed a series of preliminary material tests with such a fully constructed platform. The system was tested with materials from three different industries that could benefit from mobile additive manufacturing technology. A cement paste was tested for the construction industry, frosting for the food industry, and clay paste for the fine arts industry. Next, a statistical experimental analysis was performed to determine the optimum printing parameters to obtain geometrical accuracy of the object being printed. The independent variables chosen for the material and the printing platform included the material type, percent concentration of dry material to wetting agent, layer height, layer width, and printing speed. Multiple samples were printed for each combination of independent variables. The dependent variables, maximum taper angle and x-y-z measurements, were then found from the printed samples. Principal Component Analysis was performed on the taper angle and x-y-z measurements to create a single index which represented the error in print quality. A slightly modified 2 k factorial design was then used to determine which printing parameters and material type significantly affected the error index. Finally, response surface methodology along with the method of steepest ascent was used to identify the optimum printing parameters.

As a very fast and non-invasive examination, conventional X-ray radiography is well established as the first line diagnostic imaging method of the human bone system. While major bone injuries such as fractures and dislocations are usually easily detectable on conventional X-ray images, more subtle injuries such as microfractures are often missed, leading to mistreatment and potential long-term consequences. The technology of Photon-Counting Dual-Energy Radiography (PCDER) yields the possibility to decompose conventional X-ray images into basis material images such as bone- and soft-tissue-equivalence images. The obtained basis material images offer significant advantages in terms of image contrast and image details over the raw attenuation image which shows an overlap of bone and soft tissue. Whereas the advantages of bone- and soft-tissue-equivalence images have been broadly discussed referring to bone subtraction images in the detection of pulmonary diseases, this method has not been considered for the analysis of musculoskeletal images until present. In this study we show that basis component equivalence images have high potential to improve the diagnostic accuracy of the detection of minor bone lesions during clinical trauma imaging. A reader study performed by three experienced radiologists compares the image quality of basis material images to a standard radiograph image of a non-fractured cadaveric hand.

Background Lymph nodes (LN) are examined in every computed tomography (CT) scan. Until now, an evaluation is only possible based on morphological criteria. With dual-energy CT (DECT) systems, iodine concentration (IC) can be measured which could conduct in an improved diagnostic evaluation of LNs. Purpose To define standard values for IC of cervical, axillary, and inguinal LNs in DECT. Material and Methods Imaging data of 297 patients who received a DECT scan of the neck, thorax, abdomen–pelvis, or a combination of those in a portal-venous phase were retrospectively collected from the institutional PACS. No present history of malignancy, inflammation, or trauma in the examined region was present. For each examined region, the data of 99 patients were used. The IC of the three largest LNs, the main artery, the main vein, and a local muscle of the examined area was measured, respectively. Results Normalization of the IC of LNs to the artery, vein, muscle, or a combination of those did not lead to a decreased value-range. The smallest range and confidence interval (CI) of IC was found when using absolute values of IC for each region. Hereby, mean values (95% CI) for IC of LN were found: 2.09 mg/mL (2.00–2.18 mg/mL) for neck, 1.24 mg/mL (1.16–1.33 mg/mL) for axilla, and 1.11 mg/mL (1.04–1.17 mg/mL) for groin. Conclusion The present study suggests standard values for IC of LNs in dual-layer CT could be used to differentiate between healthy and pathological lymph nodes, considering the used contrast injection protocol.

Background X-ray dark-field radiography takes advantage of the wave properties of x-rays, with a relatively high signal in the lungs due to the many air-tissue interfaces in the alveoli. Purpose To describe the qualitative and quantitative characteristics of x-ray dark-field images in healthy human subjects. Materials and Methods Between October 2018 and January 2020, patients of legal age who underwent chest CT as part of their diagnostic work-up were screened for study participation. Inclusion criteria were a normal chest CT scan, the ability to consent, and the ability to stand upright without help. Exclusion criteria were pregnancy, serious medical conditions, and changes in the lung tissue, such as those due to cancer, pleural effusion, atelectasis, emphysema, infiltrates, ground-glass opacities, or pneumothorax. Images of study participants were obtained by using a clinical x-ray dark-field prototype, recently constructed and commissioned at the authors' institution, to simultaneously acquire both attenuation-based and dark-field thorax radiographs. Each subject's total dark-field signal was correlated with his or her lung volume, and the dark-field coefficient was correlated with age, sex, weight, and height. Results Overall, 40 subjects were included in this study (average age, 62 years ± 13 [standard deviation]; 26 men, 14 women). Normal human lungs have high signal, while the surrounding osseous structures and soft tissue have very low and no signal, respectively. The average dark-field signal was 2.5 m-1 ± 0.4 of examined lung tissue. There was a correlation between the total dark-field signal and the lung volume (r = 0.61, P < .001). No difference was found between men and women (P = .78). Also, age (r = -0.18, P = .26), weight (r = 0.24, P = .13), and height (r = 0.01, P = .96) did not influence dark-field signal. Conclusion This study introduces qualitative and quantitative values for x-ray dark-field imaging in healthy human subjects. The quantitative x-ray dark-field coefficient is independent from demographic subject parameters, emphasizing its potential in diagnostic assessment of the lung. ©RSNA, 2021 See also the editorial by Hatabu and Madore in this issue.

Several anatomic risk factors associated with patellofemoral disorders have been described. The purpose of this study was to analyze the relationship between bony parameters commonly used to analyze and define patellofemoral malalignment. Patients with patellofemoral disorders presenting between 2016 and 2018 who underwent a standardized radiographic workup including conventional radiographs, weight bearing full-leg radiographs, magnetic resonance imaging (MRI) of the knee, and torsional analysis using hip–knee–ankle MRI were initially included. Patients with a history of lower extremity fracture and a history of surgical procedures affecting bony alignment or partial/total arthroplasty were subsequently excluded. Radiographs and MRI of all included patients were analyzed by four independent observers. Parameters of interest were: femoral torsion, tibial torsion, trochlear dysplasia, tibial tuberosity–trochlear groove (TT–TG) distance, and frontal mechanical axis. All parameters were compared between patients with low grade and high grade trochlear dysplasia as well as between female and male patients. Correlation of continuous variables was assessed with the Pearson correlation coefficient. A binary logistic regression model was used for the calculation of odds ratio between different parameters. Interclass correlation coefficients (ICC) were calculated to determine the interobserver reproducibility. A total of 151 patients could be included for detailed analysis. Group comparison revealed that patients with high grade trochlear dysplasia showed significantly higher values for femoral torsion (low grade: 9.8° ± 11.0°, high grade: 16.8° ± 11.5°; p

Evaluation of sparse sampling computed tomography (SpSCT) regarding subjective and objective image criteria for the detection of pulmonary embolism (PE) at different simulated dose levels. Computed tomography pulmonary angiography (CTPA) scans of 20 clinical patients were used to obtain simulated low-dose scans with 100%–50%–25%–12.5%–6.3%–3.1% of the clinical dose, resulting in a total of six dose levels (DL). From these full sampling (FS) data, every second (2-SpSCT) or fourth (4-SpSCT) projection was used to obtain simulated sparse sampling scans. Each image set was evaluated by four blinded radiologists regarding subjective image criteria (artifacts, image quality) and diagnostic performance (confidence, sensitivity, specificity, accuracy, and area under the curve). Additionally, the contrast-to-noise ratio (CNR) was evaluated for objective image quality. Sensitivity was 100% with 2-SpSCT and 4-SpSCT at the 25% DL and the 12.5% DL for all localizations of PE (one subgroup 98.5%). With FS, the sensitivity decreased to 90% at the 12.5% DL. 2-SpSCT and 4-SpSCT showed higher values for sensitivity, specificity, accuracy, and the area under the curve at all DL compared with FS. Subjective image quality was significantly higher for 4-SpSCT compared with FS at each dose level (p

This prospective trial aimed to investigate whether tumor-specific cKIT and PDGFRA mutations can be detected and quantified in circulating tumor (ct)DNA in patients with active GIST, and whether detection indicates disease activity. We included 25 patients with active disease and cKIT or PDGFRA mutations detected in tissue. Mutant ctDNA was detected in the peripheral blood plasma using allele-specific ligation (L-)PCR and droplet digital (d)PCR. CtDNA harboring tumor-specific cKIT or PDGFRA mutations was detected at least once in 16 out of 25 patients using L-PCR (64%) and in 20 out of 25 patients with dPCR (80%). Using dPCR, the absolute numbers of ctDNA fragments (DNA copies/ml) and the mutant allele frequency (MAF; in percent of wild-type control) strongly correlated with tumor size expressed as RECIST1.1 sum of diameter (SOD) in mm (ρ = 0.3719 and 0.408, respectively, p < 0.0001) and response status (ρ = 0.3939 and 0.392, respectively, p < 0.0001 and p < 0.001). Specificity of dPCR for detection of progression was 79.2% with a sensitivity of 55.2% and dPCR discriminated CR from active disease with a specificity of 96% and s sensitivity of 44.7%. With L-PCR, correlations of MAF with tumor size and response status were less prominent. Serial ctDNA measurement reflected individual disease courses over time. Targeted panel sequencing of four patients detected additional driver mutations in all cases and secondary resistance mutations in two cases. Thus, ctDNA indicates disease activity in patients with GIST and should be incorporated as companion biomarker in future prospective trials.

To investigate the utility of quantitative dual-energy spectral CT derived iodine concentration (IC), in comparison with conventional CT attenuation, for the differentiation of pulmonary metastases from different primary malignancies.CT scans were performed on a dual-layer spectral CT. We retrospectively evaluated pulmonary metastases of 130 patients (77 men and 53 women, mean age 63, range 22-87) with primary bone (OS) (osteosarcoma; n = 6), breast (invasive-ductal adenocarcinoma; n = 17), colorectal (CRC) (adenocarcinoma; n = 27), head and neck (HNC) (squamous cell carcinoma; n = 17), kidney (RCC) (clear-cell renal cell carcinoma; n = 10), lung (adenocarcinoma; n = 12), pancreato-biliary (PBC) (adenocarcinoma; n = 18), prostate (adenocarcinoma; n = 5), soft tissue (undifferentiated pleomorphic sarcoma; n = 6), skin (malignant melanoma; n = 6), and urinary tract (transitional-cell carcinoma; n = 6) malignancies. Quantitative IC and conventional CT numbers (HU) were extracted and normalized to the thoracic aorta. Differences between the groups were assessed by pairwise t-tests with Holm-Sidak post-hoc p-value adjustment for multiple comparisons. Diagnostic accuracy was evaluated by receiver operating characteristic (ROC) analysis.Significant differences in IC and HU were noted for pulmonary metastases from RCC (IC: 2.83 mg/ml; HU: 93.12) versus breast cancer (IC: 1.47 mg/ml, adjusted p 0.05; HU: 59.57, adjusted p 0.05), CRC (IC: 1.23 mg/ml, adjusted p 0.001; HU: 49.82, adjusted p 0.001) and HNC (IC: 1.54 mg/ml, adjusted p 0.05; HU: 58.91, adjusted p 0.01). Based on IC alone, significant differences were further observed between metastatic lesions from CRC versus OS (IC: 2.36 mg/ml, adjusted p 0.001), PBC (IC: 2.16 mg/ml, adjusted p 0.001) and urinary tract carcinoma (IC: 2.21 mg/ml, adjusted p 0.05). Based on IC and HU, pulmonary metastases from OS, HNC and RCC may be differentiated from other pulmonary metastases (area under ROC curve, 0.69-0.79). The diagnostic accuracy to discriminate between pulmonary metastases from PBC and those from other malignancies was significantly higher based on IC as compared to HU (area under ROC curve, 0.66; p 0.05); no significant differences in diagnostic accuracy were noted for other differentiations.Our findings demonstrate the utility of both dual-energy CT derived quantitative IC and conventional CT attenuation values for the differential diagnosis in suspected pulmonary metastases of unknown origin, however giving preference to the use of IC.

SummaryBackgroundDiseases of the respiratory system are leading global causes of chronic morbidity and mortality. While advanced medical imaging technologies of today deliver detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection and/or follow-ups is still lacking. Here, we report on the first human application of a novel modality, namely X-ray dark-field chest imaging, which might fill this gap. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest X-rays, and yet requires only a fraction of the dose applied in computed tomography (CT).MethodsFor this first clinical evaluation, we have built a novel dark-field chest X-ray system, which is also capable of simultaneously acquiring a conventional thorax radiograph (7 seconds, 0·035 mSv effective dose). Representing a major medical condition, we selected chronic obstructive pulmonary disease as study subject to obtain a first impression of potential diagnostic benefits relevant to humans. For a collective of 77 patients with different disease stages, X-ray dark-field- and CT-images were acquired and visually assessed by 5 readers. In addition, pulmonary function tests were performed for every patient. The individual data sets were evaluated in a statistical work-up using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison.FindingsCompared to CT-based parameters (quantitative emphysema: ρ=–0·27, p=0·0893 and visual emphysema: ρ=–0·45, p=0·0028), the dark-field signal (ρ=0·62, pInterpretationX-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema as it provides relevant information representing the structural condition of lung parenchyma. Significant diagnostic benefits are also expected for other lung disorders.FundingEuropean Research Council, Royal Philips, Karlsruhe Nano Micro Facility.Research in contextEvidence before this studyWith a rising number of examinations in the last decades, X-rays play an indispensable role in clinical routine. Contrast formation in medical X-ray imaging such as radiography, fluoroscopy, and computed tomography is based on attenuation, which generally benefits from large differences in atomic number and/or mass density between involved materials. If these conditions are not prevalent, or the resolution of the imaging system is not sufficient, diagnostic capabilities are limited. However, attenuation is not the only physical effect X-rays are subjected to when penetrating matter. Variations in an object’s electron density lead to refraction and coherent small-angle scattering of incident X-rays. Phase-sensitive imaging techniques can detect these wave-optical phenomena, yielding additional object information. The dark-field signal, being a function of small-angle scattering, can provide structural information on the micron scale, generally below the resolution limit of the imaging system. Due to their very stringent requirements to X-ray source coherence, these techniques were originally limited to large-scale synchrotron facilities. The proposal of a three-grating interferometer in 2006, however, enabled the use of low-brilliance sources for X-ray phase-contrast imaging and thereby paved the way into the clinics. Such an apparatus elegantly allows the simultaneous acquisition of the conventional attenuation, differential phase-contrast, and novel dark-field signals. In a compact table-top system suitable for investigating murine disease models, numerous studies on pulmonary disorders such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumothorax, ventilator-associated lung injury, lung cancer, and pneumonia have been conducted and demonstrated a broad diagnostic value of the dark-field modality in particular. Adapting the system to enable imaging of the human body is a technical challenge due to limitations of the micrometer-fine, high aspect ratio grating structures in terms of fabricable size and performance at clinically relevant X-ray energies. The first evidences that these limitations are manageable were delivered in 2017 and 2018 by in-vivo porcine and human cadaver studies with an experimental prototype system.Added value of this studyWith this work we present the first X-ray dark-field chest images of human subjects in-vivo and demonstrate the method’s feasibility in a clinical surrounding. To enable this study, we have conceived, constructed, and commissioned a custom-built first demonstrator system suitable for patient use. This includes satisfying clinical demands regarding safety, usability, acquisition time, radiation dose, field of view, and image quality. This study marks the transition from investigating artificially induced disease models to evaluating the modality’s actual diagnostic performance in patients.Implications of all available evidenceOur findings indicate that X-ray dark-field radiography provides image-type information of the lungs’ underlying microstructure in humans. In view of the strong link between alveolar structure and the functional condition of the lung, this capability is highly relevant for respiratory medicine and might help to establish a better understanding of pulmonary disorders. With regard to early detection of COPD, which is generally accompanied by structural impairments of the lung, this novel technique might support resolving the prevalent under-diagnosis reported in literature. With an effective dose significantly lower (about a factor of hundred) compared to thorax computed tomography, dark-field radiography could be used as broadly deployed screening tool.

Objective Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. Methods Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen’s kappa. Results Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. Conclusion X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. Key Points • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

Radical cystectomy (Cx) is the standard of care for muscle-invasive bladder cancer (BCa). In locally advanced pT4 BCa the oncologic outcome is inexplicit but Cx may be necessary for palliation.The aim of this retrospective study was to evaluate the outcomes of Cx performed in patients with locally advanced pT4 BCa and to identify patient subgroups with improved outcome.Between 2008 and 2017, we identified 76 of 905 patients who underwent Cx for pT4 BCa at a single tertiary referral center. The physical patients' status was estimated according to the American Society of Anesthesiologists (ASA) classification. For the classification of postoperative complication rates, the Clavien-Dindo grading was used. Time-to-event variables with log-rank statistics were calculated with the use of the Kaplan-Meier method.Median age was 74 years (range 42-90). Preoperatively, the physical status was estimated poor in 40 (52%) patients (ASA-score of ≥3). Overall, 19 (25%) patients had pT4b BCa, 41 (54%) patients were lymph node positive (c/pN+) and 14 (18%) patients had distant metastases (c/pM+). Within 30 and 90 days after surgery, 21% and 30% of the patients, respectively, developed severe complications (Clavien-Dindo grade ≥3). Overall, 30- and 90-day mortality rates were 9% and 11%, respectively. Moreover, 86% and 75% of patients who died within 30 and 90 days after surgery, respectively, had an ASA-score ≥3. At a median postoperative follow-up of 8 months (range 0-85), 53 (70%) patients have died. During the follow-up period, 46% of the patients died due to progressive disease, 16% died of a noncancer-specific cause, and for 8% of the patients, the reason remains unknown. Median overall survival (OS) and cancer-specific survival were 13.0 and 16.0 months, respectively. In subgroup analyses ASA-score ≥3 and hemoglobin11.7 g/dl was significantly associated with poor OS. No statistically significant differences were detected between subgroups.Cx performed in patients with locally advanced pT4 BCa is associated with an increased mortality rate within 90 days postoperatively. Our study revealed that the ASA-score is a relevant and easily available tool to rate the patient´s condition and estimate postoperative outcome.

Objective The aim of this study was to evaluate the potential of x-ray dark-field radiography for the noninvasive detection of monosodium urate (MSU) crystals as a novel diagnostic tool for gout. Materials and methods Contrast-to-noise ratios of MSU crystals in conventional radiography and dark-field radiography have been compared in a proof of principle measurement. Monosodium urate crystals have been injected into mouse legs in an ex vivo experimental gout setup. Three radiologists independently evaluated the images for the occurrence of crystal deposits in a blinded study for attenuation images only, dark-field images only, and with both images available for a comprehensive diagnosis. All imaging experiments have been performed at an experimental x-ray dark-field setup with a 3-grating interferometer, a rotating anode tube (50 kVp), and a photon-counting detector (effective pixel size, 166 μm). Results X-ray dark-field radiography provided a strong signal increase for MSU crystals in a physiological buffer solution compared with conventional attenuation radiography with a contrast-to-noise ratio increase from 0.8 to 19.3. Based on conventional attenuation images only, the reader study revealed insufficient diagnostic performance (sensitivity, 11%; specificity, 92%) with poor interrater agreement (Cohen's coefficient κ = 0.031). Based on dark-field images, the sensitivity increased to 100%, specificity remained at 92%, and the interrater agreement increased to κ = 0.904. Combined diagnosis based on both image modalities maximized both sensitivity and specificity to 100% with absolute interrater agreement (κ = 1.000). Conclusions X-ray dark-field radiography enables the detection of MSU crystals in a mouse-based gout model. The simultaneous avaliability of a conventional attenuation image together with the dark-field image provides excellent detection rates of gout deposits with high specificity.

Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo–activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60–70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%–90%] for the INT arm and 33% (95% CI, 5%–68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood. Conclusions: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.

Dual Energy CT is a modern imaging technique that is utilized in clinical practice to acquire spectral information for various diagnostic purposes including the identification, classification, and characterization of different liver lesions. It provides additional information that, when compared to the information available from conventional CT datasets, has the potential to benefit existing computer vision techniques by improving their accuracy and reliability. In order to evaluate the additional value of spectral versus conventional datasets when being used as input for machine learning algorithms, we implemented a weakly-supervised Convolutional Neural Network (CNN) that learns liver lesion localization and classification without pixel-level ground truth annotations. We evaluated the lesion classification (healthy, cyst, hypodense metastasis) and localization performance of the network for various conventional and spectral input datasets obtained from the same CT scan. The best results for lesion localization were found for the spectral datasets with distances of 8.22 ± 10.72 mm, 8.78 ± 15.21 mm and 8.29 ± 12.97 mm for iodine maps, 40 keV and 70 keV virtual mono-energetic images, respectively, while lesion localization distances of 10.58 ± 17.65 mm were measured for the conventional dataset. In addition, the 40 keV virtual mono-energetic datasets achieved the highest overall lesion classification accuracy of 0.899 compared to 0.854 measured for the conventional datasets. The enhanced localization and classification results that we observed for spectral CT data demonstrates that combining machine-learning technology with spectral CT information may improve the clinical workflow as well as the diagnostic accuracy.

To evaluate the clinical potential of dual layer computed tomography (DLCT) for posterior fusions of the thoracic and lumbar spine and determine the optimal keV-settings for an improved overall image quality and effective reduction of metal artefacts affecting the implant inheriting vertebral body, the spinal canal, the paravertebral muscle and aorta.Twenty patients with posterior thoracic and lumbar spinal fusion, who underwent a 120kVp- DLCT scan were included in this study. Two independent readers evaluated axial 0.9 mm slides with soft tissue and bone window settings. Image quality of the conventional scan was compared to virtual monoenergetic images (VMI) at 40, 60, 80, 100,120, 140, 160, 180 and 200 keV. Diagnostic image quality was assessed on a four point Likert-scale overall, as well as specifically for the implant inheriting bone, paravertebral muscle, spinal canal or aorta. The Hounsfield Units (HU) of the area with the most pronounced streak artefact as well as HU of a reference area containing fat and muscle were documented for each keV-setting and compared to the conventional image. SNR and CNR were calculated for each of the four anatomic areas. Statistical analysis was conducted for the total collective and separately for the thoracic and lumbar spine level.Starting from 80 keV qualitative analysis revealed significant improvement of overall image quality and benefit for each tissue separately compared to the conventional images (CI) (p-values in the range from0.001 to 0.005). 180 keV was considered the optimal monoenergetic setting regarding the overall image quality. For the assessment of the implant inheriting bone, the spinal canal, paravertebral muscle and aorta 200, 180, 160 and 180 keV were rated to be the most sufficient. Our results reveal high inter-reader agreement for qualitative evaluations (intra-class correlation coefficients0.927; p 0.05). HU values within the most pronounced streak artefact increased significantly with higher keV (p 0.001), while there was no significant alteration of HU within the reference area. A decrease in SNR and CNR for higher VMI was revealed by our results.VMIs of higher energies provide significant reduction of metallic artefacts from posterior spinal fusions. Dedicated keV settings to evaluate either the implant inheriting bone, the spinal canal,adjacent muscle or aorta - structures, which are frequently of particular interest after posterior spinal fusion - are recommended. In addition, an optimal keV for an improved overall image quality is proposed.

Purpose To evaluate virtual-non-contrast (VNC) images obtained from clinical triphasic scans with a dual-layer spectral computed tomography system regarding accuracy of iodine subtraction. Material and methods From September to December 2016, 62 consecutive patients who underwent a clinical routine triphasic CT examination were included into this retrospective study. VNC images based on the arterial and portal venous phase were generated. For every patient and every contrast phase, a region-of-interest (ROI) was defined in aorta, liver, renal cortex, spongious bone, fat, muscle and fluid (i.e. gallbladder, urinary bladder), resulting in 2170 ROIs. VNC images were compared to true-non-contrast (TNC) images regarding difference in attenuation. Consistency between VNC images obtained from the arterial and portal venous phase as well as the influence of the initial attenuation on respective VNC images were evaluated. Results Comparison of HU in VNC and TNC images showed a high accuracy of iodine elimination. Mean difference between TNC and VNC images was only 0.5 ± 8.5 HU and >90% of all comparisons showed a difference of less than 15 HU. For all tissues but spongious bone, mean absolute difference between TNC and VNC images was below 10 HU. VNC images derived from the arterial and the portal venous phase showed excellent correlation. The quality of iodine removal in VNC images was not influenced by the original contrast enhancement. However, VNC images cannot be used for evaluation of iodine removal in bone as bone and iodine can hardly be differentiated via spectral CT. Conclusion VNC imaging in DL-CT is a promising tool for daily clinical routine. As non-enhanced CT images are essential in multiple clinical situations, the permanent availability of VNC images with dual-layer spectral CT will result in a substantial reduction of radiation exposure and an increased diagnostic value of monophasic contrast-enhanced CT scans.

Purpose Evaluation of the influence of iterative reconstruction, tube settings and patient habitus on the accuracy of iodine quantification with dual-layer spectral CT (DL-CT). Material and methods A CT abdomen phantom with different extension rings and four iodine inserts (1, 2, 5 and 10 mg/ml) was scanned on a DL-CT. The phantom was scanned with tube-voltages of 120 and 140 kVp and CTDIvol of 2.5, 5, 10 and 20 mGy. Reconstructions were performed for eight levels of iterative reconstruction (i0-i7). Diagnostic dose levels are classified depending on patient-size and radiation dose. Results Measurements of iodine concentration showed accurate and reliable results. Taking all CTDIvol-levels into account, the mean absolute percentage difference (MAPD) showed less accuracy for low CTDIvol-levels (2.5 mGy: 34.72%) than for high CTDIvol-levels (20 mGy: 5.89%). At diagnostic dose levels, accurate quantification of iodine was possible (MAPD 3.38%). Level of iterative reconstruction did not significantly influence iodine measurements. Iodine quantification worked more accurately at a tube voltage of 140 kVp. Phantom size had a considerable effect only at low-dose-levels; at diagnostic dose levels the effect of phantom size decreased (MAPD Conclusion With DL-CT, even low iodine concentrations can be accurately quantified. Accuracies are higher when diagnostic radiation doses are employed.

Objectives: Meniscal extrusion in MRI is normally described as pathologic finding and associated with a loss of function of the affected meniscus. We hypothesize that in healthy knees there is also physiological meniscal extrusion as a functional adjustment on various load bearing condition. Therefore[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

Objectives To evaluate sparse sampling computed tomography (SpSCT) for detection of endoleak after endovascular aortic repair (EVAR) at different dose levels in terms of subjective image criteria and diagnostic accuracy. Methods Twenty clinically indicated computed tomography aortic angiography (CTA) scans were used to obtain simulated low-dose scans with 100%, 50%, 25%, 12.5% and 6.25% of the applicated clinical dose, resulting in five dose levels (DL). From full sampling (FS) data sets, every second (2-SpSCT) or fourth (4-SpSCT) projection was used to generate simulated sparse sampling scans. All examinations were evaluated by four blinded radiologists regarding subjective image criteria and diagnostic performance. Results Sensitivity was higher than 93% in 4-SpSCT at the 25% DL which is the same as with FS at full dose (100% DL). High accuracies and relative high AUC-values were obtained for 2- and 4-SpSCT down to the 12.5% DL, while for FS similar values were shown down to 25% DL only. Subjective image quality was significantly higher for 4-SpSCT compared to FS at each dose level. More than 90% of all cases were rated with a high or medium confidence for FS and 2-SpSCT at the 50% DL and for 4-SpSCT at the 25% DL. At DL 25% and 12.5%, more cases showed a high confidence using 2- and 4-SpSCT compared with FS. Conclusions Via SpSCT, a dose reduction down to a 25% dose level (mean effective dose of 1.49 mSv in the current study) for CTA is possible while maintaining high image quality and full diagnostic confidence.

Rationale and Objectives The study aimed to improve the detection of pulmonary embolism via an iodine contrast enhancement tool in patients who underwent suboptimal enhanced computed tomography angiography (CTA). Materials and Methods We evaluated the CT examinations of 41 patients who underwent CTA for evaluation of the pulmonary arteries which suffered from suboptimal contrast enhancement. The contrast enhancement of the reconstructed images was increased via a post-processing tool (vContrast). Image noise and contrast-to-noise ratio (CNR) were assessed in eight different regions: main pulmonary artery, right and left pulmonary arteries, right and left segment arteries, muscle, subcutaneous fat, and bone. For subjective image assessment, three experienced radiologists evaluated the diagnostic quality. Results While employing the post-processing algorithm, the CNR for contrast-filled lumen and thrombus/muscle improves significantly by a factor of 1.7 (CNR without vContrast = 8.48 ± 6.79/CNR with vContrast = 14.46 ± 5.29) ( P 0.01). No strengthening of artifacts occurred, and the mean Hounsfield unit values of the muscle, subcutaneous fat, and the bone showed no significant changes. Subjective image analysis illustrated a significant improvement using post-processing for clinically relevant criteria such as diagnostic confidence. Conclusions vContrast makes CT angiograms with inadequate contrast applicable for diagnostic evaluation, offering an improved visualization of the pulmonary arteries. In addition, vContrast can help in the significant reduction of the iodine contrast material.