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Objective: Quantification of tumour burden in oncology requires accurate and reproducible evaluation. The current standard is RECIST measurement with its inherent disadvantages. Volumetric analysis is an alternative for therapy monitoring. The aim of this study was to evaluate the feasibility of volumetric analysis of lymph node metastases using a software prototype in a follow-up setting.Methods: MSCT was performed in 50 patients covering the chest, abdomen and pelvis. A total of 174 suspicious lymph nodes were evaluated by two radiologists regarding short axis diameters and volumetric analysis using semi-automated software. Quality of segmentation, time, maximum diameter and volume were documented. Variability of the derived change rates was computed as the standard deviation of the difference of the obtained respective change rates.Results: The software performance provides robust volumetric analysis. Quality of segmentation was rated acceptable to excellent in 76-79% by each reader. Mean time spent per lesion was 38 s. The variability of change in effective diameters was 10.6%; for change rates of RECIST maximum diameter variability was 27.5%.Conclusion: Semi-automated volumetric analysis allows fast and convenient segmentation of most lymph node metastases. Compared with RECIST the inter-observer-variability in baseline and follow-up is reduced. This should principally allow subtle changes to be subclassified within the RECIST stable range as minor response [-15% to +10%]. [ABSTRACT FROM AUTHOR]

The purpose was to evaluate ex-vivo a prototype of a novel biopsy canula under CT fluoroscopy-guidance in ventilated porcine lung explants in respiratory motion simulations. Using an established chest phantom for porcine lung explants, n = 24 artificial lesions consisting of a fat-wax-Lipiodol mixture (approx. 70HU) were placed adjacent to sensible structures such as aorta, pericardium, diaphragm, bronchus and pulmonary artery. A piston pump connected to a reservoir beneath a flexible silicone reconstruction of a diaphragm simulated respiratory motion by rhythmic inflation and deflation of 1.5 L water. As biopsy device an 18-gauge prototype biopsy canula with a lancet-like, helically bended cutting edge was used. The artificial lesions were punctured under CT fluoroscopy-guidance (SOMATOM Sensation 64, Siemens, Erlangen, Germany; 30mAs/120 kV/5 mm slice thickness) implementing a dedicated protocol for CT fluoroscopy-guided lung biopsy. The mean-diameter of the artificial lesions was 8.3 +/- 2.6 mm, and the mean-distance of the phantom wall to the lesions was 54.1 +/- 13.5 mm. The mean-displacement of the lesions by respiratory motion was 14.1 +/- 4.0 mm. The mean-duration of CT fluoroscopy was 9.6 +/- 5.1 s. On a 4-point scale (1 = central; 2 = peripheral; 3 = marginal; 4 = off target), the mean-targeted precision was 1.9 +/- 0.9. No misplacement of the biopsy canula affecting adjacent structures could be detected. The novel steerable biopsy canula proved to be efficient in the ex-vivo set-up. The chest phantom enabling respiratory motion and the steerable biopsy canula offer a feasible ex-vivo system for evaluating and training CT fluoroscopy-guided lung biopsy adapted to respiratory motion. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. Methods: CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. Results: Manual measurements of the tumor longest diameter were significantly (p <0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p <0.001) and area (0.995 vs. 0.988; p =0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2–3 times that of semi-automated measurement. Conclusions: By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients. [Copyright &y& Elsevier]

This paper assesses the impact of the length of maternity leave on children's health outcomes in the long-run. My quasi-experimental design evaluates an expansion in maternity leave coverage from two to six months, which occurred in the Federal Republic of Germany in 1979. The expansion came into effect after a sharp cutoff date and significantly increased the time working mothers stayed at home with their newborns during the first six months after childbirth. Using this cutoff date as a source of exogenous variation, I exploit German hospital registry data, which contains detailed information on the universe of inpatients' diagnoses from 1995-2014. By tracking the health of treated and control children from age 16 up to age 35, this study provides new insights into the trajectory of health differentials over the life-cycle. I find that the legislative change generated positive long-term health effects: My intention-to-treat estimates show that children born after the implementation of the reform experience fewer hospital admissions and are less likely to be diagnosed with mental and behavioral disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting., Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST., Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements., Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach., Key Points: ► Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients ► Manual lymph node evaluation with uni-dimensional parameters is inferior to semi-automatic analysis in a multicenter setting ► Semi-automatic quantitative software tools should be introduced in clinical study evaluation., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To investigate measurement accuracy in terms of precision and inter-rater variability in the simultaneous volumetric assessment of lung, liver and lymph node metastasis size change over time in comparison to RECIST 1.1., Materials and Methods: Three independent readers evaluated multislice CT data from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually (RECIST 1.1) and by volumetry with semi-automated software. The quality of segmentation and need for manual adjustments were recorded. Volumes were converted to effective diameters to allow comparison to RECIST. For statistical assessment of precision and interobserver agreement, the Wilcoxon-signed rank test and Bland-Altman plots were utilized., Results: The quality of segmentation after manual correction was acceptable to excellent in 95 % of lesions and manual corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective) relative measurement deviation (p <.001). Inter-reader median variation coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for different lesion types (p < .001). The limits of agreement were ± 9.8 to ± 11.2 % for volumetric assessment., Conclusion: Superior precision and inter-rater variability of volumetric over manual measurement of lesion change over time was demonstrated in a whole body setting., (© Georg Thieme Verlag KG Stuttgart · New York.)

Radiotherapy for organs with respiratory motion has motivated the development of dynamic volume lung imaging with computed tomography (4D-CT) or magnetic resonance imaging (4D-MRI). 4D-CT can be realized in helical (continuous couch translation during image acquisition) or cine mode (translation step-by-step), either acquired prospectively or reconstructed retrospectively with temporal resolutions of up to 250 msec. Long exposure times result in high radiation dose and restrict 4D-CT to specific indications (ie, radiotherapy planning). Dynamic MRI accelerated by parallel imaging and echo sharing reaches temporal resolutions of up to 10 images/sec (2D+t) or 1 volume/s (3D+t) that allow analyzing respiratory motion of the lung and its tumors. Near isotropic 4D-MRI can be used to assess tumor displacement, chest wall invasion, and segmental respiratory mechanics. Limited temporal resolution of dynamic volume acquisitions (in their current implementation) may lead to an overestimation of tumor size, as the mass is volume averaged into many voxels during motion. Nevertheless, 4D-MRI allows for repeated and prolonged measurements without radiation exposure and therefore appears to be appropriate for patient selection in motion-adapted radiotherapy as well as for a broad spectrum of scientific applications., (Copyright © 2010 Wiley-Liss, Inc.)

Orbital floor fractures, often combined with zygomatic fractures, are common fractures of the midface. Surgery of orbital fractures is done to free incarcerated or prolapsed orbital tissue and to restore the anatomic skeletal size of the orbit. Lyodura was a standard for the reconstruction of the orbital floor until cases of Creutzfeldt-Jakob disease were reported, so that polydioxanone (PDS) is widely used today. However, infections around the implant are reported. In a randomized controlled clinical study on 24 patients with orbital floor defects of approximately 1 cm, we evaluated the use of a collagen membrane compared with a PDS foil. Computed tomography controls and ophthalmologic examinations were performed after 6 months in 10 patients per group.Intraoperative complications occurred neither in the collagen membrane group nor in the PDS group. In case of orbital rim fractures, the collagen membrane could additionally cover these defects. Perioperatively and postoperatively, no complications such as infections were observed. After 6 months, computed tomography controls revealed a complete reposition of orbital tissue and even bone regeneration in both groups. Diplopia and hypoesthesia were completely reversed after half a year.Smaller defects (up to 1 cm) of the orbital floor can be restored with a PDS foil or a collagen membrane. However, for larger defects, stability may not be sufficient.

Purpose: To compare the reproducibility (r) of CT value measurement of pulmonary nodules using volumetry software (LungCare, LC) and manual ROIs (mROI)., Materials and Methods: 54 artificial nodules in a chest phantom were scanned three times with CT. CT values were measured with LC and mROI. The intrascan-r was assessed with three measurements in the first scan, and the interscan-r with measurements in three consecutive scans (one observer). Intrascan-r und interobserver-r (two obs.) were assessed in the first scan and in contrast-enhanced CT of 51 nodules from 15 patients (kernels b50f and b80f). Intrascan-r and interscan-r were described as the mean range and interobserver-r as the mean difference of CT values. The significance of differences was tested using t-test and sign test., Results: Reproducibility was significantly higher for volumetry-based measurements in both artificial and patient nodules (range 0.11 vs. 6.16 HU for intrascan-r, 2.22 vs. 7.03 HU for interscan-r, difference 0.11 vs. 18.42 HU for interobserver-r; patients: 1.78 vs. 13.19 HU (b50f-Kernel) and 1.88 vs. 27.4 HU (b80f-Kernel) for intrascan-r, 3.71 vs. 22.43 HU for interobserver-r). Absolute CT values differed significantly between convolution kernels (pat./mROI: 29.3 [b50f] and 151.9 HU [b80f] pat./LC: 5 [b50f] and 147 HU [b80f])., Conclusion: The reproducibility of volumetry-based measurements of CT values in pulmonary nodules is significantly higher and should therefore be recommended, e. g. in dynamic chest CT protocols. Reproducibility does not depend on absolute CT values.

Magnetic resonance imaging of inhaled fluorinated inert gases ((19)F-MRI) such as sulfur hexafluoride (SF(6)) allows for analysis of ventilated air spaces. In this study, the possibility of using this technique to image lung function was assessed. For this, (19)F-MRI of inhaled SF(6) was compared with respiratory gas analysis, which is a global but reliable measure of alveolar gas fraction. Five anesthetized pigs underwent multiple-breath wash-in procedures with a gas mixture of 70% SF(6) and 30% oxygen. Two-dimensional (19)F-MRI and end-expiratory gas fraction analysis were performed after 4 to 24 inhaled breaths. Signal intensity of (19)F-MRI and end-expiratory SF(6) fraction were evaluated with respect to linear correlation and reproducibility. Time constants were estimated by both MRI and respiratory gas analysis data and compared for agreement. A good linear correlation between signal intensity and end-expiratory gas fraction was found (correlation coefficient 0.99+/-0.01). The data were reproducible (standard error of signal intensity 8% vs. that of gas fraction 5%) and the comparison of time constants yielded a sufficient agreement. According to the good linear correlation and the acceptable reproducibility, we suggest the (19)F-MRI to be a valuable tool for quantification of intrapulmonary SF(6) and hence lung function.

Purpose: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT)., Methods and Materials: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility., Results: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16)., Conclusions: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement.

Oncological patient care requires long term follow-up in order to estimate effectiveness of existing and new treatment choices. Image-based assessment of whole body tumour burden is commonly used for that purpose. The WHO response criteria were established in 1979 proposing bi-dimensional tumor measurements. New RECIST guidelines appeared in 2000 relying on only the longest diameter (uni-dimensional) measurements. Obviously, a change in tumour size is only one potential surrogate for therapy response which not necessarily reflects the biologic activity of the tumour or the effect of particular therapy. Thus, the evaluation of biological, metabolic or molecular properties of a tumor and its changes might be an attractive means to assess the response to therapy sensitively and early.

Chest wall invasion by a tumour and mediastinal masses are known to benefit from the superior soft tissue contrast of magnetic resonance imaging (MRI). However, helical computed tomography (CT) (i.e. with multiple row detector systems) remains the modality of choice to detect and follow lesions of the lung parenchyma. Since minimizing radiation exposure plays a minor role in oncologic patients, there are only few routine indications for which MRI of lung parenchyma is preferred to CT. This includes whole body MR imaging for staging or scientific studies with frequent follow-up examinations. MR-based lung imaging in this context was always considered as a weak point. Depending on the sequence technique and imaging conditions (i.e. ability to hold breath) the threshold for lung nodule detection with MRI using 1.5 T systems was estimated to be above 3-4 mm. The feasibility of lung MRI at 0.3-0.5 T and 3.0 T systems has been demonstrated. The clinical value of time-resolved lung nodule perfusion analysis cannot yet be determined, although the combination of perfusion characteristics with morphologic criteria contributes to estimate the integrity of a solitary lesion.

A method of four-dimensional (4D) magnetic resonance imaging (MRI) has been implemented and evaluated. It consists of retrospective sorting and slice stacking of two-dimensional (2D) images using an external signal for motion monitoring of the object to be imaged. The presented method aims to determine the tumour trajectories based on a signal that is appropriate for monitoring the movement of the target volume during radiotherapy such that the radiation delivery can be adapted to the movement. For evaluation of the 4D-MRI method, it has been applied to a dynamic lung phantom, which exhibits periodic respiratory movement of a porcine heart-lung explant with artificial pulmonary nodules. Anatomic changes of the lung phantom caused by respiratory motion have been quantified, revealing hysteresis. The results demonstrate the feasibility of the presented method of 4D-MRI. In particular, it enables the determination of trajectories of periodically moving objects with an uncertainty in the order of 1 mm.

Objective: Medullary thyroid carcinoma (MTC) is often associated with gain-of-function mutations in the RET proto-oncogene, which is found in all hereditary cases and most sporadic cases. The activated RET receptor tyrosine kinase can be inhibited by tyrosine kinase inhibitors in vitro. We evaluated the efficacy of treatment with imatinib mesylate, a tyrosine kinase inhibitor, in patients with advanced MTC., Design and Patients: In this open-label clinical trial, nine patients, eight with sporadic and one with hereditary MTC, with unresectable, measurable, progressive metastases were treated with imatinib mesylate 600 mg daily. The tumour response to imatinib was evaluated after 3, 6 and 12 months by computed tomography and after 1 month by (18)F-fluoro-2-deoxy D-glucose position-emission tomographic scanning. The median duration of therapy was 8 months., Results: Overall, stable disease occurred in five patients for up to 6 months and in one patient for up to 12 months, with a median duration of progression-free survival of 6 months. Four patients had progressive disease after 12 months. One patient stopped therapy after 2 weeks because of worsening of diarrhoea. Therapy was well tolerated, although transient mild-to-moderate nausea (n = 3), oedema (n = 3), diarrhoea (n = 2) and skin rash (n = 2) were observed., Conclusion: Imatinib mesylate is well tolerated, no tumour remission was observed, only transient stable disease was achieved in some patients with advanced MTC.

Objectives: To compare the image quality and lesion contrast of lung MRI using 5 different pulse sequences at 1.5 T and 3 T., Materials and Methods: Lung MRI was performed at 1.5 T and 3 T using 5 pulse sequences which have been previously proposed for lung MRI: 3D volumetric interpolated breath-hold examination (VIBE), true fast imaging with steady-state precession (TrueFISP), half-Fourier single-shot turbo spin-echo (HASTE), short tau inversion recovery (STIR), T2-weighted turbo spin-echo (TSE). In addition to 4 healthy volunteers, 5 porcine lungs were examined in a dedicated chest phantom. Lung pathology (nodules and infiltrates) was simulated in the phantom by intrapulmonary and intrabronchial injections of agarose. CT was performed in the phantom for correlation. Image quality of the sequences was ranked in a side-by-side comparison by 3 blinded radiologists regarding the delineation of pulmonary and mediastinal anatomy, conspicuity of pulmonary nodules and infiltrates, and presence of artifacts. The contrast of nodules and infiltrates (CNODULES and CINFILTRATES) defined by the ratio of the signal intensities of the lesion and adjacent normal lung parenchyma was determined., Results: There were no relevant differences regarding the preference for the individual sequences between both field strengths. TSE was the preferred sequence for the visualization of the mediastinum at both field strengths. For the visualization of lung parenchyma the observers preferred TrueFISP in volunteers and TSE in the phantom studies. At both field strengths VIBE achieved the best rating for the depiction of nodules, whereas HASTE was rated best for the delineation of infiltrates. TrueFISP had the fewest artifacts in volunteers, whereas STIR showed the fewest artifacts in the phantom. For all but the TrueFISP sequence the lesion contrast increased from 1.5 T to 3 T. At both field strengths VIBE showed the highest CNODULES (6.6 and 7.1) and HASTE the highest CINFILTRATES (6.1 and 6.3)., Conclusion: The imaging characteristics of different pulse sequences used for lung MRI do not substantially differ between 1.5 T and 3 T. A higher lesion contrast can be expected at 3 T.