First-order evolution equations with dynamic boundary conditions.

In this paper, we introduce a general framework to study linear first-order evolution equations on a Banach space X with dynamic boundary conditions, that is with boundary conditions containing time derivatives. Our method is based on the existence of an abstract Dirichlet operator and yields finally to equivalent systems of two simpler independent equations. In particular, we are led to an abstract Cauchy problem governed by an abstract Dirichlet-to-Neumann operator on the boundary space ∂X. Our approach is illustrated by several examples and various generalizations are indicated. This article is part of the theme issue 'Semigroup applications everywhere'.

Correction for X-Ray Scatter and Detector Crosstalk in Dark-Field Radiography.

Dark-field radiography, a new X-ray imaging method, has recently been applied to human chest imaging for the first time. It employs conventional X-ray devices in combination with a Talbot-Lau interferometer with a large field of view, providing both attenuation and dark-field radiographs. It is well known that sample scatter creates artifacts in both modalities. Here, we demonstrate that also X-ray scatter generated by the interferometer as well as detector crosstalk create artifacts in the dark-field radiographs, in addition to the expected loss of spatial resolution. We propose deconvolution-based correction methods for the induced artifacts. The kernel for detector crosstalk is measured and fitted to a model, while the kernel for scatter from the analyzer grating is calculated by a Monte-Carlo simulation. To correct for scatter from the sample, we adapt an algorithm used for scatter correction in conventional radiography. We validate the obtained corrections with a water phantom. Finally, we show the impact of detector crosstalk, scatter from the analyzer grating and scatter from the sample and their successful correction on dark-field images of a human thorax.

Correction for Mechanical Inaccuracies in a Scanning Talbot-Lau Interferometer.

Grating-based X-ray phase-contrast and in particular dark-field radiography are promising new imaging modalities for medical applications. Currently, the potential advantage of dark-field imaging in early-stage diagnosis of pulmonary diseases in humans is being investigated. These studies make use of a comparatively large scanning interferometer at short acquisition times, which comes at the expense of a significantly reduced mechanical stability as compared to tabletop laboratory setups. Vibrations create random fluctuations of the grating alignment, causing artifacts in the resulting images. Here, we describe a novel maximum likelihood method for estimating this motion, thereby preventing these artifacts. It is tailored to scanning setups and does not require any sample-free areas. Unlike any previously described method, it accounts for motion in between as well as during exposures.

Imaging in inflammatory arthritis: progress towards precision medicine.

Imaging techniques such as ultrasonography and MRI have gained ground in the diagnosis and management of inflammatory arthritis, as these imaging modalities allow a sensitive assessment of musculoskeletal inflammation and damage. However, these techniques cannot discriminate between disease subsets and are currently unable to deliver an accurate prediction of disease progression and therapeutic response in individual patients. This major shortcoming of today's technology hinders a targeted and personalized patient management approach. Technological advances in the areas of high-resolution imaging (for example, high-resolution peripheral quantitative computed tomography and ultra-high field MRI), functional and molecular-based imaging (such as chemical exchange saturation transfer MRI, positron emission tomography, fluorescence optical imaging, optoacoustic imaging and contrast-enhanced ultrasonography) and artificial intelligence-based data analysis could help to tackle these challenges. These new imaging approaches offer detailed anatomical delineation and an in vivo and non-invasive evaluation of the immunometabolic status of inflammatory reactions, thereby facilitating an in-depth characterization of inflammation. By means of these developments, the aim of earlier diagnosis, enhanced monitoring and, ultimately, a personalized treatment strategy looms closer.

Association of Structural Entheseal Lesions With an Increased Risk of Progression From Psoriasis to Psoriatic Arthritis.

OBJECTIVE: To test whether the presence of structural entheseal lesions in psoriasis patients influences the risk of progression to psoriatic arthritis (PsA). METHODS: We conducted a prospective cohort study of psoriasis patients without clinical evidence of musculoskeletal involvement who underwent baseline assessment of structural entheseal lesions and volumetric bone mineral density (vBMD) at entheseal and intraarticular sites by high-resolution peripheral quantitative computed tomography. Adjusted relative risks of developing PsA associated with baseline vBMD and the presence of structural entheseal lesions were calculated using multivariable Cox regression models. RESULTS: The cohort included 114 psoriasis patients (72 men and 42 women) with a mean ± SD follow-up duration of 28.2 ± 17.7 months, during which 24 patients developed PsA (9.7 per 100 patient-years [95% confidence interval (95% CI) 6.2-14.5]). Patients with structural entheseal lesions were at higher risk of developing PsA compared to patients without such lesions (21.4 per 100 patient-years [95% CI 12.5-34.3]; hazard ratio [HR] 5.10 [95% CI 1.53-16.99], P = 0.008). With respect to vBMD, a 1-SD increase in entheseal, but not intraarticular, vBMD was associated with an ~30% reduced risk of progression to PsA. Especially, higher cortical vBMD at entheseal segments was associated with a lower risk of developing PsA (HR 0.32 per 1 SD [95% CI 0.14-0.71]), and the association remained robust after multiple imputation of missing data (HR 0.64 [95% CI 0.42-0.98]). CONCLUSION: The presence of structural entheseal lesions as well as low cortical vBMD at entheseal segments are associated with an increased risk of developing PsA in patients with psoriasis.

Cinematic rendering in rheumatic diseases-Photorealistic depiction of pathologies improves disease understanding for patients.

Background: Patient education is crucial for successful chronic disease management. Current education material for rheumatic patients however rarely includes images of disease pathologies, limiting patients' disease understanding. Cinematic rendering (CR) is a new tool that allows segmentation of standard medical images (DICOMs) into pictures that illustrate disease pathologies in a photorealistic way. Thus CR has the potential to simplify and improve the explanation of disease pathologies, disease activity and disease consequences and could therefore be a valuable tool to effectively educate and inform patients about their rheumatic and musculoskeletal disease (RMD). Objectives: To examine the feasibility of creating photorealistic images using CR from RMD patients depicting typical rheumatic disease pathologies and, in a second step to investigate the patient-perceived educational potential of these photorealistic images in clinical routine. Methods: We selected conventional, high-resolution (HR) and positron emission tomography (PET) computed tomography (CT) images of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and giant cell arteritis (GCA) that showed typical respective disease pathologies. These images were segmented using CR technique. In a prospective study, physicians used CR-enhanced and conventional original images to explain the depicted pathognomonic pathologies to patients with the respective rheumatic disease. Patients were then asked to complete a questionnaire evaluating the perceived usefulness of being presented with CR-enhanced images to better understand their underlying disease. Results: CR images were successfully generated from above mentioned CT methods. Pathologies such as bone erosions, bony spurs, bone loss, ankylosis, and PET-based inflammation could be visualized in photorealistic detail. A total of 79 patients (61% females) with rheumatic diseases (RA 29%, PsA 29%, axSpA 24%, GCA 18%) were interviewed and answered the quantitative questionnaire. Mean age was 55.4 ± 12.6 years. Irrespective of disease, all patients agreed or highly agreed that CR-based images help to improve disease understanding, should be shown at disease onset, provide a rationale to regularly take medication and would like to have access to their own CR-enhanced images. Conclusion: Conventional disease images can successfully be turned into photorealistic disease depictions using CR. Patients perceived CR images as a valuable addition to current patient education, enabling personalized disease education and potentially increased medication adherence.

Dark-field chest X-ray imaging for the assessment of COVID-19-pneumonia.

BACKGROUND: Currently, alternative medical imaging methods for the assessment of pulmonary involvement in patients infected with COVID-19 are sought that combine a higher sensitivity than conventional (attenuation-based) chest radiography with a lower radiation dose than CT imaging. METHODS: Sixty patients with COVID-19-associated lung changes in a CT scan and 40 subjects without pathologic lung changes visible in the CT scan were included (in total, 100, 59 male, mean age 58 ± 14 years). All patients gave written informed consent. We employed a clinical setup for grating-based dark-field chest radiography, obtaining both a dark-field and a conventional attenuation image in one image acquisition. Attenuation images alone, dark-field images alone, and both displayed simultaneously were assessed for the presence of COVID-19-associated lung changes on a scale from 1 to 6 (1 = surely not, 6 = surely) by four blinded radiologists. Statistical analysis was performed by evaluation of the area under the receiver-operator-characteristics curves (AUC) using Obuchowski's method with a 0.05 level of significance. RESULTS: We show that dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and that the combination of both is superior to one imaging modality alone. Furthermore, a quantitative image analysis shows a significant reduction of dark-field signals for COVID-19-patients. CONCLUSIONS: Dark-field imaging complements and improves conventional radiography for the visualisation and detection of COVID-19-pneumonia.

Computed tomography (CT) imaging uses X-rays to obtain images of the inside of the body. It is used to look at lung damage in patients with COVID-19. However, CT imaging exposes the patient to a considerable amount of radiation. As radiation exposure can lead to the development of cancer, exposure should be minimised. Conventional plain X-ray imaging uses lower amounts of radiation but lacks sensitivity. We used dark-field chest X-ray imaging, which also uses low amounts of radiation, to assess the lungs of patients with COVID-19. Radiologists identified pneumonia in patients more easily from dark-field images than from usual plain X-ray images. We anticipate dark-field X-ray imaging will be useful to follow-up patients suspected of having lung damage.

Leveraging medical imaging for medical education - A cinematic rendering-featured lecture.

BACKGROUND: The integration of medical imaging into anatomical education offers advantages in understanding and learning. However, spatial orientation with conventional (2D) imaging data is challenging, and the students' ability to imagine structures in three dimensions is individual. In addition, the quality of current volume rendering methods is limited. OBJECTIVE: We tested Cinematic Rendering (CR), a novel visualization technique that provides photorealistic volume rendering, in the setting of an interactive anatomy lecture with first-year undergraduate medical and dental students. Our goal was to estimate the acceptance and positive effects CR adds to the subjects. METHODS: A total of 120 students were surveyed with specifically designed self-assessment questionnaires on the use of CR as a tool in anatomical education. RESULTS: Of 120 participating students (87 medical and 33 dental) a large majority of 95.9% (Q3) experienced CR as helpful to understand anatomy better. Overall a large majority of the students experienced CR as helpful for learning and understanding, 85% saw an improvement in anatomical education through the integration of CR (Q3-6) and could also imagine using CR as a self-study tool on an electronic device. CONCLUSION: Our undergraduate medical and dental students experienced CR as a beneficial tool for anatomical education in the chosen setting (lecture) and see further opportunities for the sensible use of this technique. Future research on the topic should include other application possibilities as well.

X-ray scattering in single- and dual-source CT.

For medical imaging applications, such as cardiac imaging, dual-source computed tomography (CT) improves the temporal resolution by the simultaneous use of two cone beams, which acquire twice as many projections as single-source CT does within the same time interval. Besides this advantage, a drawback of such a system is additional x-ray scatter originating from the extra (cross-illuminating) cone beam. In this work, a comparison with single-source CT images is performed under same-dose conditions for two different thorax phantoms, and for different cone beam angles corresponding to a coverage of 20, 40, 80, and 160 mm on the rotation axis (z coverage). As a general result, the HU-magnitude of scatter-induced streak and cupping artifacts scale almost proportional to the illuminated volume. In dual-source CT, cross scatter induces a further factor of almost 2 in the scaling of artifacts in comparison to single-source CT. For all examined systems, the scatter-induced noise reduces the contrast-to-noise ratio (CNR). In the case of an ideal scatter correction, the CNR is reduced even more, but contrast and CNR can be restored by an additional x-ray dose. With a 32-slice single-source CT (z overage of 20 mm) taken as a reference, a corresponding dual-source CT requires 7% more dose to maintain the same CNR. A CT system with a z coverage of 40, 80, and 160 mm requires 8%, 23%, and 54% more dose in a single-source configuration, respectively, and 20%, 47%, and 102% more dose in a dual-source configuration, respectively. In conclusion, a dual-source CT is comparable to a single-source CT with twice the z coverage concerning image degradation by scatter.

X-ray imaging performance of scintillator-filled silicon pore arrays.

The need for fine detail visibility in various applications such as dental imaging, mammography, but also neurology and cardiology, is the driver for intensive efforts in the development of new x-ray detectors. The spatial resolution of current scintillator layers is limited by optical diffusion. This limitation can be overcome by a pixelation, which prevents optical photons from crossing the interface between two neighboring pixels. In this work, an array of pores was etched in a silicon wafer with a pixel pitch of 50 microm. A very high aspect ratio was achieved with wall thicknesses of 4-7 microm and pore depths of about 400 microm. Subsequently, the pores were filled with Tl-doped cesium iodide (CsI:Tl) as a scintillator in a special process, which includes powder melting and solidification of the CsI. From the sample geometry and x-ray absorption measurement the pore fill grade was determined to be 75%. The scintillator-filled samples have a circular active area of 16 mm diameter. They are coupled with an optical sensor binned to the same pixel pitch in order to measure the x-ray imaging performance. The x-ray sensitivity, i.e., the light output per absorbed x-ray dose, is found to be only 2.5%-4.5% of a commercial CsI-layer of similar thickness, thus very low. The efficiency of the pores to transport the generated light to the photodiode is estimated to be in the best case 6.5%. The modulation transfer function is 40% at 4 lp/mm and 10%-20% at 8 lp/mm. It is limited most likely by the optical gap between scintillator and sensor and by K-escape quanta. The detective quantum efficiency (DQE) is determined at different beam qualities and dose settings. The maximum DQE(0) is 0.28, while the x-ray absorption with the given thickness and fill factor is 0.57. High Swank noise is suspected to be the reason, mainly caused by optical scatter inside the CsI-filled pores. The results are compared to Monte Carlo simulations of the photon transport inside the pore array structure. In addition, some x-ray images of technical and anatomical phantoms are shown. This work shows that scintillator-filled pore arrays can provide x-ray imaging with high spatial resolution, but are not suitable in their current state for most of the applications in medical imaging, where increasing the x-ray doses cannot be tolerated.

A New Approach for Photorealistic Visualization of Rendered Computed Tomography Images.

OBJECTIVE: Classical single-colored or multicolored 3-dimensional (3D) visualization of sectional images lacked in being realistic and revealed limited anatomical discrimination. Recently, a new technique called cinematic volume rendering for 3D reconstruction of computed tomography has been developed. The aim of this study was to analyze this new visualization algorithm from a technical perspective and to investigate potential benefits for neurosurgical applications. METHODS: A standard test in computer graphics called Cornell Box was adapted and applied for reproducibility of light effects in cinematic rendering opposed to classic rendering methods. Simulation of distinct camera effects such as variable apertures, exposition time, optics, and surface refinements are presented in a human skull, respectively. Postprocessing capabilities allow for immediate clinical use. RESULTS: This volume-rendering technique generates cadaver-like 3D reconstructions. By considering complex interactions between a scanned object and dynamic light patterns, a cinematic illumination of a 3D surface reconstruction can be achieved. A spinal tumor case and a complex intracranial carotid artery aneurysm are presented, comparing all available rendering techniques. Cinematic rendering results in greater spatial discrimination of neighboring anatomical structures. CONCLUSIONS: This technical and clinical description focuses on the neurosurgical relevance of a new rendering technique. Considering the improved image impression of cinematic rendering and viewers' perception, it seems likely that the technique will gain wide acceptance in the clinical routine.

Shaping the future through innovations: From medical imaging to precision medicine.

Medical images constitute a source of information essential for disease diagnosis, treatment and follow-up. In addition, due to its patient-specific nature, imaging information represents a critical component required for advancing precision medicine into clinical practice. This manuscript describes recently developed technologies for better handling of image information: photorealistic visualization of medical images with Cinematic Rendering, artificial agents for in-depth image understanding, support for minimally invasive procedures, and patient-specific computational models with enhanced predictive power. Throughout the manuscript we will analyze the capabilities of such technologies and extrapolate on their potential impact to advance the quality of medical care, while reducing its cost.

Remote computing environment compensating for brain shift.

OBJECTIVE: Anatomical and functional image data become invalid during an operation due to brain shift. Compensation is achieved by using intraoperative imaging to update anatomical information. To accelerate the registration and visualization of pre- and intraoperative image data, the presented work focuses on remote computing capabilities. The underlying framework efficiently combines local desktop computers and remote high-end graphics workstations exploiting expensive hardware. METHODS: By performing all computations on the remote computer, the MR volumes are rigidly aligned via voxel-based registration. Using graphics hardware for acceleration, all interpolation operations are performed with 3D texture-mapping hardware. A new approach then transforms functional markers from preoperative measurements to the intraoperative situation using an automatic tracking algorithm to identify corresponding sulci. Communicating Java viewers are suggested for analyzing the results interactively on a local computer, with all calculations being performed exclusively on the remote computer. RESULTS: The suggested approach was successfully applied in 5 cases using MR data containing functional markers of MEG and fMRI measurements identifying eloquent brain areas. Remote large-scale graphics hardware was thereby efficiently made available for fast registration and interactive direct volume rendering in neurosurgery. CONCLUSION: Overall, the presented framework demonstrates efficient access of expensive high-end hardware remotely controlled by thin clients, and further emphasizes the need to compensate for brain shift in functional neuronavigation.

Noise properties of grating-based x-ray phase contrast computed tomography.

PURPOSE: To investigate the properties of tomographic grating-based phase contrast imaging with respect to its noise power spectrum and the energy dependence of the achievable contrast to noise ratio. METHODS: Tomographic simulations of an object with 11 cm diameter constituted of materials of biological interest were conducted at different energies ranging from 25 to 85 keV by using a wave propagation approach. Using a Monte Carlo simulation of the x-ray attenuation within the object, it is verified that the simulated measurement deposits the same dose within the object at each energy. RESULTS: The noise in reconstructed phase contrast computed tomography images shows a maximum at low spatial frequencies. The contrast to noise ratio reaches a maximum around 45 keV for the simulated object. The general dependence of the contrast to noise on the energy appears to be independent of the material. Compared with reconstructed absorption contrast images, the reconstructed phase contrast images show sometimes better, sometimes worse, and sometimes similar contrast to noise, depending on the material and the energy. CONCLUSIONS: Phase contrast images provide additional information to the conventional absorption contrast images and might thus be useful for medical applications. However, the observed noise power spectrum in reconstructed phase contrast images implies that the usual trade-off between noise and resolution is less efficient for phase contrast imaging compared with absorption contrast imaging. Therefore, high-resolution imaging is a strength of phase contrast imaging, but low-resolution imaging is not. This might hamper the clinical application of the method, in cases where a low spatial resolution is sufficient for diagnosis.

Sensitivity of photon-counting based K-edge imaging in X-ray computed tomography.

The feasibility of K-edge imaging using energy-resolved, photon-counting transmission measurements in X-ray computed tomography (CT) has been demonstrated by simulations and experiments. The method is based on probing the discontinuities of the attenuation coefficient of heavy elements above and below the K-edge energy by using energy-sensitive, photon counting X-ray detectors. In this paper, we investigate the dependence of the sensitivity of K-edge imaging on the atomic number Z of the contrast material, on the object diameter D , on the spectral response of the X-ray detector and on the X-ray tube voltage. We assume a photon-counting detector equipped with six adjustable energy thresholds. Physical effects leading to a degradation of the energy resolution of the detector are taken into account using the concept of a spectral response function R(E,U) for which we assume four different models. As a validation of our analytical considerations and in order to investigate the influence of elliptically shaped phantoms, we provide CT simulations of an anthropomorphic Forbild-Abdomen phantom containing a gold-contrast agent. The dependence on the values of the energy thresholds is taken into account by optimizing the achievable signal-to-noise ratios (SNR) with respect to the threshold values. We find that for a given X-ray spectrum and object size the SNR in the heavy element's basis material image peaks for a certain atomic number Z. The dependence of the SNR in the high- Z basis-material image on the object diameter is the natural, exponential decrease with particularly deteriorating effects in the case where the attenuation from the object itself causes a total signal loss below the K-edge. The influence of the energy-response of the detector is very important. We observed that the optimal SNR values obtained with an ideal detector and with a CdTe pixel detector whose response, showing significant tailing, has been determined at a synchrotron differ by factors of about two to three. The potentially very important impact of scattered X-ray radiation and pulse pile-up occurring at high photon rates on the sensitivity of the technique is qualitatively discussed.

Performance simulation of an x-ray detector for spectral CT with combined Si and Cd[Zn]Te detection layers.

The most obvious problem in obtaining spectral information with energy-resolving photon counting detectors in clinical computed tomography (CT) is the huge x-ray flux present in conventional CT systems. At high tube voltages (e.g. 140 kVp), despite the beam shaper, this flux can be close to 109 Mcps mm⁻² in the direct beam or in regions behind the object, which are close to the direct beam. Without accepting the drawbacks of truncated reconstruction, i.e. estimating missing direct-beam projection data, a photon-counting energy-resolving detector has to be able to deal with such high count rates. Sub-structuring pixels into sub-pixels is not enough to reduce the count rate per pixel to values that today's direct converting Cd[Zn]Te material can cope with (≤ 10 Mcps in an optimistic view). Below 300 µm pixel pitch, x-ray cross-talk (Compton scatter and K-escape) and the effect of charge diffusion between pixels are problematic. By organising the detector in several different layers, the count rate can be further reduced. However this alone does not limit the count rates to the required level, since the high stopping power of the material becomes a disadvantage in the layered approach: a simple absorption calculation for 300 µm pixel pitch shows that the required layer thickness of below 10 Mcps/pixel for the top layers in the direct beam is significantly below 100 µm. In a horizontal multi-layer detector, such thin layers are very difficult to manufacture due to the brittleness of Cd[Zn]Te. In a vertical configuration (also called edge-on illumination (Ludqvist et al 2001 IEEE Trans. Nucl. Sci. 48 1530-6, Roessl et al 2008 IEEE NSS-MIC-RTSD 2008, Conf. Rec. Talk NM2-3)), bonding of the readout electronics (with pixel pitches below 100 µm) is not straightforward although it has already been done successfully (Pellegrini et al 2004 IEEE NSS MIC 2004 pp 2104-9). Obviously, for the top detector layers, materials with lower stopping power would be advantageous. The possible choices are, however, quite limited, since only 'mature' materials, which operate at room temperature and can be manufactured reliably should reasonably be considered. Since GaAs is still known to cause reliability problems, the simplest choice is Si, however with the drawback of strong Compton scatter which can cause considerable inter-pixel cross-talk. To investigate the potential and the problems of Si in a multi-layer detector, in this paper the combination of top detector layers made of Si with lower layers made of Cd[Zn]Te is studied by using Monte Carlo simulated detector responses. It is found that the inter-pixel cross-talk due to Compton scatter is indeed very high; however, with an appropriate cross-talk correction scheme, which is also described, the negative effects of cross-talk are shown to be removed to a very large extent.