Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer-results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group.

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.

Calcium scoring using 64-slice MDCT, dual source CT and EBT: a comparative phantom study.

PURPOSE: Assessment of calcium scoring (Ca-scoring) on a 64-slice multi-detector computed tomography (MDCT) scanner, a dual-source computed tomography (DSCT) scanner and an electron beam tomography (EBT) scanner with a moving cardiac phantom as a function of heart rate, slice thickness and calcium density. METHODS AND MATERIALS: Three artificial arteries with inserted calcifications of different sizes and densities were scanned at rest (0 beats per minute) and at 50-110 beats per minute (bpm) with an interval of 10 bpm using 64-slice MDCT, DSCT and EBT. Images were reconstructed with a slice thickness of 0.6 and 3.0 mm. Agatston score, volume score and equivalent mass score were determined for each artery. A cardiac motion susceptibility (CMS) index was introduced to assess the susceptibility of Ca-scoring to heart rate. In addition, a difference (Delta) index was introduced to assess the difference of absolute Ca-scoring on MDCT and DSCT with EBT. RESULTS: Ca-score is relatively constant up to 60 bpm and starts to decrease or increase above 70 bpm, depending on scoring method, calcification density and slice thickness. EBT showed the least susceptibility to cardiac motion with the smallest average CMS-index (2.5). The average CMS-index of 64-slice MDCT (9.0) is approximately 2.5 times the average CMS-index of DSCT (3.6). The use of a smaller slice thickness decreases the CMS-index for both CT-modalities. The Delta-index for DSCT at 0.6 mm (53.2) is approximately 30% lower than the Delta-index for 64-slice MDCT at 0.6 mm (72.0). The Delta-indexes at 3.0 mm are approximately equal for both modalities (96.9 and 102.0 for 64-slice MDCT and DSCT respectively). CONCLUSION: Ca-scoring is influenced by heart rate, slice thickness and modality used. Ca-scoring on DSCT is approximately 50% less susceptible to cardiac motion as 64-slice MDCT. DSCT offers a better approximation of absolute calcium score on EBT than 64-slice MDCT when using a smaller slice thickness. A smaller slice thickness reduces the susceptibility to cardiac motion and reduces the difference between CT-data and EBT-data. The best approximation of EBT on CT is found for DSCT with a slice thickness of 0.6 mm.

Dose reduction and image quality in MDCT colonography using tube current modulation.

OBJECTIVE: The purpose of our study was to evaluate the dose reduction potential of combined online (x- and y-axes) and topogram-based (l) X-ray tube current modulation in CT colonography in a screening population. MATERIALS AND METHODS: Eighty asymptomatic individuals underwent CT colonography screening for colon polyps. A 16-MDCT scanner (Somatom Sensation 16) was used. Forty patients were examined at 120 kVp and 120 effective mAs (supine) and 40 effective mAs (prone) using online x- and y-axis tube current modulation. Another 40 patients were scanned using combined x-, y-, and z-axis tube current modulation. Individual patient radiation exposure was determined using the dose-length product. Image noise was determined by Hounsfield unit measurements in the colonic lumen at four anatomic levels. Image quality was rated on a 5-point confidence scale by two independent reviewers. The unpaired Student's t test (for radiation dose, image noise) and Wilcoxon's test (for image quality) were used to test for statistically significant differences between these values. RESULTS: Radiation dose was significantly lower in the patient group scanned with x-, y-, and z-axis tube current modulation than in the group scanned with x- and y-axis tube current modulation (supine: 4.24 vs 6.50 mSv, p < 0.0001; prone: 1.61 vs 2.38 mSv, p < 0.0001). Radiation dose was reduced by 35% (supine) and 33% (prone). No statistically significant difference was seen in overall image noise (supine: 15.9 vs 16.3 H, p = 0.13; prone: 23.5 vs 24.8 H, p = 0.44) or image quality (supine: 4.6 vs 4.5, p = 0.62; prone: 3.5 vs 3.6, p = 0.54). CONCLUSION: Combined x-, y-, and z-axis tube current modulation leads to a significant reduction of radiation exposure in CT colonography without loss of image quality.

Crystallographic and morphological characterization of thin pentacene films on polycrystalline copper surfaces.

The degree of crystallinity, the structure and orientation of crystallites, and the morphology of thin pentacene films grown by vapor deposition in an ultrahigh vacuum environment on polycrystalline copper substrates have been investigated by x-ray diffraction and tapping-mode scanning force microscopy (TM-SFM). Depending on the substrate temperature during deposition, very different results are obtained: While at 77 K a long-range order is missing, the films become crystalline at elevated temperatures. From a high-resolution x-ray-diffraction profile analysis, the volume-weighted size of the crystallites perpendicular to the film surface could be determined. This size of the crystallites increases strongly upon changing temperature between room temperature and 333 K, at which point the size of individual crystallites typically exceeds 100 nm. In this temperature region, three different polymorphs are identified. The vast majority of crystallites have a fiber texture with the (001) net planes parallel to the substrate. In this geometry, the molecules are oriented standing up on the substrate (end-on arrangement). This alignment is remarkably different from that on single-crystalline metal surfaces, indicating that the growth is not epitaxial. Additionally, TM-SFM images show needlelike structures which suggest the presence of at least one additional orientation of crystallites (flat-on or edge-on). These results indicate that properties of thin crystalline pentacene films prepared on technologically relevant polycrystalline metal substrates for fast electronic applications may be compromised by the simultaneous presence of different local molecular aggregation states at all temperatures.

Core excitations of biphenyl.

High-resolution C(1s) near-edge X-ray absorption and X-ray photoionization spectra of the free biphenyl molecule are presented and theoretically analyzed in order to allow an assignment of the observed spectral features. Finite lifetime broadening, a high density of vibrational states, and a strong overlap of contributions from chemically different carbon atom sites only partially allow resolving the vibrational fine structure. However, the shape and width of the spectral profiles are strongly determined by both chemical shifts and vibronic effects. In particular, different from photoionization of valence levels, both types of core level spectra do not contain contributions from dihedral modes which are related to the twisting motion of the two phenyl rings. Contrary to naphthalene, C-H stretching modes are significantly enhanced in the core excitation spectra of biphenyl while the contributions from C-C stretching modes are reduced.

Aorto-iliac multidetector-row CT angiography with low kV settings: improved vessel enhancement and simultaneous reduction of radiation dose.

The aim of the study was to implement an abdominal CT angiography protocol using 100 kVp and to compare SNR and CNR, as well as subjective image quality, to a standard CT angiography protocol using 120 kVp on a 16 detector-row CT scanner. Forty-eight patients were referred for routine abdominal CT angiography on a 16 detector-row CT scanner. Patients were scanned using either 120 or 100 kVp at constant mAs settings. Vessel opacification was provided by automated contrast injection using similar injection protocols. Density measurements were performed along the aorto-iliac axis with SNR and CNR calculation. In addition, the estimated effective patient radiation dose was calculated. Results of both protocols were compared. The 100-kVp protocol (432+/-80 HU) showed a significantly higher vessel density than the 120-kVp (333+/-90 HU; P<0.001) protocol, corresponding to an average increase in signal intensity of 30.7%. SNR (36.0 vs 37.0) and CNR (31.1 vs 31.7) for the 100-kV protocol were not significantly lower that those for the standard protocol (P=0.79 and P=0.87), whilst the average estimated dose was significantly lower using the 100-kVp protocol (6.7+/-0.4 vs 10.1+/-1.2 mSv; P<0.0001). Tube kVp reduction from 120 to 100 kVp allows for significant reduction of patient dose in abdominal CT angiography, without significant change in SNR,CNR and image quality.

Core excitations of naphthalene: vibrational structure versus chemical shifts.

High-resolution x-ray photoelectron emission (XPS) and near-edge x-ray absorption fine structure (NEXAFS) spectra of naphthalene are analyzed in terms of the initial state chemical shifts and the vibrational fine structure of the excitations. Carbon atoms located at peripheral sites experience only a small chemical shift and exhibit rather similar charge-vibrational coupling, while the atoms in the bridging positions differ substantially. In the XPS spectra, C-H stretching modes provide important contributions to the overall shape of the spectrum. In contrast, the NEXAFS spectrum contains only vibrational progressions from particular C-C stretching modes. The accuracy of ab initio calculations of absolute electronic transition energies is discussed in the context of minute chemical shifts, the vibrational fine structure, and the state multiplicity.

The role of intermolecular polarization for the stability of lithium intercalation compounds of alpha- and beta-perylene.

Lithium intercalation compounds of alpha- and beta-perylene are investigated by photoelectron spectroscopy. Spectroscopic data together with a Born-Haber cycle provide information on the formation enthalpy of those materials. This approach allows understanding the amount of charge transferred from the alkali metal atoms to the pi system, and illuminates the role of molecular versus solid-state properties in the formation of the intercalation compounds. In the bulk of alpha-perylene material, molecular dimerization survives upon intercalation which reduces the Madelung energy of the intercalation compound but increases the electron-accepting capability of the organic system and facilitates the ionization of lithium atoms in the molecular solid environment. The lower ionization potential results in a larger charge transfer (about two electrons per molecule) in alpha-perylene compared to the monomeric system, beta-perylene.

[Automatic exposure control to reduce the dose in subsecond multislice spiral CT: phantom measurements and clinical results]. / Dosisautomatik bei der Mehrzeilenspiral-CT: Phantommessungen und klinische Ergebnisse.

PURPOSE: To investigate the potential of dose reduction in multislice spiral CT (MSCT) with automatic exposure control. MATERIALS AND METHODS: The study was performed on a Sensation 4 multislice scanner. This prototype implementation analyzed the distribution of the attenuation along the z-axis in the lateral and sagittal directions of the digital radiogram. Depending on this distribution of the attenuation, the tube current (mA) is defined for every tube rotation. In addition, the tube current was modulated during each tube rotation. First, a three step oval water phantom was measured to evaluate the potential of this method with respect to dose reduction and image quality. In a patient study (n = 26), four different scan regions (shoulder, thorax, abdomen, pelvis) were examined and dose (mAs) and image quality evaluated in comparison to examinations with a standard protocol for these regions in adults and a weight-adjusted standard protocol in children. The image quality was classified in consensus as good, sufficient and poor image quality. RESULTS: By adapting and modulating the tube current, we substantially reduced the variation of noise in one spiral scan and in one scan region of our patient collective. The dose (average mAs) was reduced by 31 % to 66 % in children (mean 44 %) and between 35 % and 64 % in adults (mean 53 %), depending on the scan region. The image quality was substantially improved in regions with high attenuation and did not suffer in low attenuation regions. CONCLUSION: The dose can be reduced substantially by an automatic exposure control including angular tube current modulation with the same or improved image quality.

Image reconstruction and performance evaluation for ECG-gated spiral scanning with a 16-slice CT system.

We present an image reconstruction approach and a performance evaluation for ECG-gate cardiac spiral scanning with recently introduced 16-slice CT equipment. We present an extension of the Adaptive Cardio Volume (ACV) reconstruction approach for ECG-gated multislice spiral scanning. We discuss the image z reformation introduced to control the spiral slice width of the final images and give an overview of the reformation functions chosen. We investigate image quality and discuss the maximum number of slices that can be reconstructed without severe cone-beam artifacts. Slice sensitivity profiles (SSPs) and transverse resolution are evaluated as a function of the patient's heart rate. We demonstrate the influence of slice width on the visualization of stents and plaques and show the impact of reduced gantry rotation time (0.42 s) on temporal resolution. Deviating from general purpose spiral scanning cone-beam reconstruction is not required for ECG-gated cardiac CT with up to 16 slices. Using the ACV approach with image reformation, SSPs are well defined and independent of the patient's heart rate. With 0.75 mm collimated slice width, the measured full width at half-maximum (FWHM) of the smallest reconstructed slice is about 0.83 mm. Using this slice width and overlapping image reconstruction, cylindrical holes 0.6-0.7 mm in diameter can be resolved in a z-resolution phantom. Adequate visualization of the coronary arteries requires reconstruction slice widths not larger than 1.5 mm. Visualization of stents and severe calcifications is significantly improved with sub-mm slice width. Experimental evidence for the theoretically predicted temporal resolution and for the variation of temporal resolution depending on the position in the field of measurement (FOM) is presented. With 0.42 s gantry rotation temporal resolution reaches its optimum of 105 ms in the center of the FOM at 81 bpm. First scans on human subjects demonstrate the potential to expand the range of heart rates accessible to routine clinical examinations. A 16-slice platform can cover the heart with sub-mm slices within short breath-hold times, allowing for improved cardiac imaging due to isotropic sub-mm spatial resolution.

Dose reduction in spiral CT angiography of thoracic outlet syndrome by anatomically adapted tube current modulation.

The aim of this study was to evaluate dose reduction in spiral CT angiography of the thoracic outlet by on-line tube-current control. Prospectively, 114 patients undergoing spiral CT angiography of the subclavian artery for thoracic outlet arterial syndromes were evaluated with and without tube-current modulation at the same session (scanning parameters for the two successive angiograms, one in the neutral position and one after the postural maneuver): 140 kV; 206 mA; scan time 0.75 s; collimation 3 mm; pitch = 1). The dose reduction system was applied in the neutral position in the first 92 consecutive patients and after postural maneuver in the remaining 22 consecutive patients. Dose reduction and image quality were analyzed in the overall study group (group 1; n = 114). The influence of the arm position was assessed in 44 of the 114 patients (group 2), matched by the transverse diameter of the upper thorax. The mean dose reduction was 33% in group 1 (range 22-40%) and 34% in group 2 (range 26-40%). In group 2 the only difference in image quality was a significantly higher frequency of graininess on low-dose scans compared with reference scans whatever the patient's arm position, graded as minimal in 38 of the 44 patients (86%). When the low-dose technique was applied after postural maneuver in group 2: (a) the mean dose reduction was significantly higher (35 vs 32% in the neutral position; p = 0.006); (b) graininess was less frequent (82 vs 91% in the neutral position); and (c) the percentage of graininess graded as minimal was significantly higher (83 vs 70% in the neutral position; p = 0.2027). On-line tube-current modulation enables dose reduction on high-quality, diagnostic spiral CT angiograms of the thoracic outlet and should be applied during data acquisition in the neutral position and after postural maneuver for optimal use.

Dose reduction in CT by anatomically adapted tube current modulation. I. Simulation studies.

Tube current modulation governed by x-ray attenuation during CT (computed tomography) acquisition can lead to noise reduction which in turn can be used to achieve patient dose reduction without loss in image quality. The potential of this technique was investigated in simulation studies calculating both noise amplitude levels and noise distribution in CT images. The dependence of noise on the inodulation function, amplitude of modulation, shape and size of the object, and possible phase shift between attenuation and modulation function were examined. Both sinusoidal and attenuation-based control functions were used to modulate tube current. Noise reduction was calculated for both ideal systems and for real systems with limited modulation amplitude. Dose reductions up to 50% can be achieved depending on the phantom geometry and tube current modulation function. Attenuation-based tube current modulation yields substantially higher reduction than fixed-shape modulation functions. Optimal results are obtained when the current is modulated as a function of the square root of attenuation. A modulation amplitude of at least 90% should be available to exploit the potential of these techniques.

Dose reduction in CT by anatomically adapted tube current modulation. II. Phantom measurements.

Theoretical considerations and simulation studies have led to the expectation that patient dose in CT (computed tomography) can be reduced significantly without a concomitant loss in image quality if tube current is modulated according to rotation angle-dependent x-ray attenuation. In this study, the simulation results presented in Part I were validated with phantoms. We used one cylindrical, two oval, and one elliptical phantom, available both as mathematical descriptions and in physical form, to mimic different parts of the human anatomy. Prototype hardware was available to control tube current on a commercial clinical CT scanner. The potential for dose reduction was evaluated for sinusoidal and attenuation-based current modulation for variable modulation amplitudes. Agreement between simulations and measured results was better than within 10%. Dose reduction values of 8%-56% were found depending on the phantom geometry and tube current modulation function. Attenuation-based tube current modulation consistently yielded higher reduction than fixed-shape sinusoidal modulation functions. For the shoulder phantom and 70% modulation amplitude, 44.6% dose reduction was measured as compared to 34.1% for sinusoidal modulation. A maximum of 56% was measured for the shoulder phantom including inserts. Specifying mAs reduction as an estimate for dose reduction proved to be a valid and conservative estimate; measured dose is reduced more strongly than the total mAs product both centrally and on average. First patient studies confirm the results of simulation and phantom studies. We conclude that attenuation-based online tube current control has great potential for reducing patient dose in CT and that it should be made generally available for clinical use.

Dose reduction in CT by on-line tube current control: principles and validation on phantoms and cadavers.

We investigated approaches to reducing the dose in CT without impairing image quality. Dose can be reduced for non-circular object cross-sections without a significant increase in noise if X-ray tube current is reduced at angular tube positions where the X-ray attenuation by the patients is small. We investigated different schemes of current modulation during tube rotation by simulation and phantom measurements. Both pre-programmed sinusoidal modulation functions and attenuation-based on-line control of the tube current were evaluated. All relevant scan parameters were varied, including constraints such as the maximum modulation amplitude. A circular, an elliptical and two oval water phantoms were used. Results were validated on six cadavers. Dose reduction of 10-45% was obtained both in simulations and in measurements for the different non-circular phantom geometries and current modulation algorithms without an increase in pixel noise values. On-line attenuation-based control yielded higher reductions than modulation by a sinusoidal curve. The maximal dose reduction predicted any simulations could not be achieved due to limits in the modulation amplitude. In cadaver studies, a reduction of typically 20-40% was achieved for the body and about 10% for the head. Variations of our technique are possible; a slight increase in nominal tube current for high-attenuation projections combined with attenuation-based current modulation still yields significant dose reduction, but also a reduction in the structured noise that may obscure diagnostic details. We conclude that a significant reduction in dose can be achieved by tube current modulation without compromising image quality. Attenuation-based on-line control and a modulation amplitude of at least 90% should be employed.

New low-contrast resolution phantoms for computed tomography.

Computed tomography (CT) has been established as a major imaging modality in diagnostic radiology. Accordingly, acceptance testing and quality control of CT scanners is of great importance. While most procedures and phantoms for testing are widely accepted, there is still discussion and uncertainty about low-contrast (LC) sensitivity. In our opinion this unsatisfactory situation is caused at least in part by the lack of suitable phantoms for LC resolution measurements. We investigated the commonly used phantoms for LC detectability, the Catphan, and for LC resolution, the ATS phantom. While the Catphan showed stable object contrasts, the ATS phantom's measured contrast exhibited a strong dependence on temperature and x-ray quality. Based on newly developed polyurethane resin materials, we designed and tested a LC resolution phantom with several different contrast steps. The object contrasts showed no dependence on temperature and beam quality. The new LC resolution phantom proved to be very suitable for measuring a scanner's low-contrast sensitivity in the image plane, one of the most important image quality parameters. To assess LC resolution in three dimensions we designed an additional phantom with rows of spherical objects. A first prototype was evaluated in a multicenter study. The setup proved to be very helpful to quantify the in-plane and axial LC sensitivity of spiral CT scan modes.

A new calibration phantom for quantitative computed tomography.

We report on a new calibration phantom for quantitative computed tomography which has been improved with respect to reference materials and geometrical setup. Instead of liquid calibration solutions, we use polyethylene-based water- and bone-equivalent plastics. The size of the phantom is considerably reduced by using only two samples. This design guarantees long-term stability and it offers advantages with respect to radiation geometry.

Vertebral bone mineral analysis: an integrated approach with CT.

In the assessment of vertebral bone mineral density (BMD) with quantitative computed tomography, accuracy is limited by systematic errors caused by beam-hardening effects and unknown marrow and fat concentrations in trabecular bone. Reproducibility depends on precise repositioning of the patient, selection of the region of interest (ROI), and apparatus stability. In an integrated approach, these error sources were taken into account. Dual-energy methods are incorporated and tested to avoid systematic errors. Contour-detection algorithms for automated ROI determination that work reliably and offer improved reproducibility and efficiency are presented. A new design of reference phantom with solid tissue-equivalent materials provides calibration in BMD units and checks apparatus stability. Dual-energy methods are necessary to achieve accuracy of 5% or better. Automated ROI definition and reference phantom methods are mandatory for reproducibility of 2% or better.

Measurement of paranasal sinus ventilation by xenon-enhanced dynamic computed tomography.

Ventilation of the paranasal sinuses plays an important role in the etiology of acute and chronic sinusitis. We present a new method to determine sinus ventilation. Two to three liters of pure stable xenon are insufflated into the sinus system, and the xenon washout is measured subsequently by dynamic CT. Gas exchange parameters for the different sinuses are obtained from the washout curves by an exponential fit. We report our preliminary clinical results. The method proved to be reliable and easy to apply. Compared with existing procedures it is the only noninvasive quantitative method for the determination of the ventilation of all paranasal sinuses.