Ultra-low-dose photon-counting CT of paranasal sinus: an in vivo comparison of radiation dose and image quality to cone-beam CT.

PURPOSE: This study investigated the differences in subjective and objective image parameters as well as dose exposure of photon-counting CT (PCCT) compared to cone-beam CT (CBCT) in paranasal sinus imaging for the assessment of rhinosinusitis and sinonasal anatomy. METHODS: This single-centre retrospective study included 100 patients, who underwent either clinically indicated PCCT or CBCT of the paranasal sinus. Two blinded experienced ENT radiologists graded image quality and delineation of specific anatomical structures on a 5-point Likert scale. In addition, contrast-to-noise ratio (CNR) and applied radiation doses were compared among both techniques. RESULTS: Image quality and delineation of bone structures in paranasal sinus PCCT was subjectively rated superior by both readers compared to CBCT (P < .001). CNR was significantly higher for photon-counting CT (P < .001). Mean effective dose for PCCT examinations was significantly lower than for CBCT (0.038 mSv ± 0.009 vs. 0.14 mSv ± 0.011; P < .001). CONCLUSION: In a performance comparison of PCCT and a modern CBCT scanner in paranasal sinus imaging, we demonstrated that first-use PCCT in clinical routine provides higher subjective image quality accompanied by higher CNR at close to a quarter of the dose exposure compared to CBCT.

Detection of Endoleaks Following Thoracic and Abdominal Aortic Endovascular Aortic Repair-: A Comparison of Standard and Dynamic 4D-Computed Tomography Angiography.

PURPOSE: Endoleaks are a common complication after endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). The detection and correct classification of endoleaks is essential for the further treatment of affected patients. However, standard computed tomography angiography (CTA) provides no hemodynamic information on endoleaks, which can result in misclassification in complex cases. The aim of this study was to compare standard CTA (sCTA) with dynamic, dual-energy CTA (dCTA) for detection and classification of endoleaks following EVAR or TEVAR. MATERIALS AND METHODS: This retrospective evaluation compared 69 sCTA diagnostic examinations performed on 50 different patients with 89 dCTA diagnostic examinations performed on 69 different patients. RESULTS: In total, 15.9% of sCTA examinations and 49.4% of dCTA examinations led to the detection of endoleaks. With sCTA, 20.0% of patients were diagnosed with endoleaks, while with dCTA, 37.7% of patients were diagnosed with endoleaks. With sCTA, mainly Type 1 endoleaks were detected, whereas, with dCTA, the types of detected endoleaks were more evenly distributed. In comparison with the literature, the frequencies of endoleak types detected with dCTA better reflect the natural distribution than the frequencies detected with standard CTA. CONCLUSION: Based on the retrospective comparative evaluation, dCTA could pose a valuable supplementary diagnostic tool resulting in a more accurate and realistic detection and classification of suspected endoleaks.

Initial experience on abdominal photon-counting computed tomography in clinical routine: general image quality and dose exposure.

OBJECTIVES: Photon-counting computed tomography has lately found its way into clinical routine. The new technique could offer substantial improvements regarding general image quality, image noise, and radiation dose reduction. This study evaluated the first abdominal examinations in clinical routine and compared the results to conventional computed tomography. METHODS: In this single-center retrospective study, 66 patients underwent photon-counting and conventional abdominal CT. Four radiologists assessed general image quality, image noise, and image artifacts. Signal-to-noise ratio and dose properties of both techniques within the clinical application were compared. An ex vivo phantom study revealed the radiobiological impact by means of DNA double-strand break foci in peripheral blood cells by enumerating γ-H2AX+53BP1 foci. RESULTS: General image quality in accordance with the Likert scale was found superior for photon-counting CT (4.74 ± 0.46 vs. 4.25 ± 0.54; p < 0.001). Signal-to-noise ratio (p < 0.001) and also dose exposure were higher for photon-counting CT (DLP: 419.2 ± 162.2 vs. 372.3 ± 236.6 mGy*cm; p = 0.0435). CT exposure resulted in significantly increased DNA damage in comparison to sham control (p < 0.001). Investigation of the average foci per cell and radiation-induced foci numbers revealed significantly elevated numbers (p = 0.004 and p < 0.0001, respectively) after photon-counting CT. CONCLUSION: Photon-counting CT in abdominal examinations showed superior results regarding general image quality and signal-to-noise ratio in clinical routine. However, this seems to be traded for a significantly higher dose exposure and corresponding double-strand break frequency. Optimization of standard protocols in further clinical applications is required to find a compromise regarding picture quality and dose exposure. KEY POINTS: • Photon-counting computed tomography promises to enhance the diagnostic potential of medical imaging in clinical routine. • Retrospective single-center study showed superior general image quality accompanied by higher dose exposure in initial abdominal PCCT protocols compared to state-of-the-art conventional CT. • A simultaneous ex vivo phantom study revealed correspondingly increased frequencies of DNA double-strand breaks after PCCT.

Photon-Counting Detector CT Virtual Monoengergetic Images for Cochlear Implant Visualization-A Head to Head Comparison to Energy-Integrating Detector CT.

Cochlear implants (CIs) are the primary treatment method in patients with profound sensorineural hearing loss. Interpretation of postoperative imaging with conventional energy-integrating detector computed tomography (EID-CT) following CI surgery remains challenging due to metal artifacts. Still, the photon-counting detector (PCD-CT) is a new emerging technology with the potential to eliminate these problems. This study evaluated the performance of virtual monoenergetic (VME) EID-CT images versus PCD-CT in CI imaging. In this cadaveric study, two temporal bone specimens with implanted CIs were scanned with EID-CT and PCD-CT. The images were assessed according to the visibility of interelectrode wire, size of electrode contact, and diameter of halo artifacts. The visibility of interelectrode wire sections was significantly higher when reviewing PCD-CT images. The difference in diameter measurements for electrode contacts between the two CT scanner modalities showed that the PCD-CT technology generally led to significantly larger diameter readings. The larger measurements were closer to the manufacturer's specifications for the CI electrode. The size of halo artifacts surrounding the electrode contacts did not differ significantly between the two imaging modalities. PCT-CT imaging is a promising technology for CI imaging with improved spatial resolution and better visibility of small structures than conventional EID-CT.

Detection of Embedded Low-level Radioactive Shrapnel after the Explosion of a Radiological Dispersal Device in Radiological Emergency Imaging.

Concern about the threat of a terrorist attack with a Radiological Dispersal Device has increased considerably over the last few years, and this comes along with an immense challenge, especially regarding medical treatment of combined injuries with incorporated radioactive fragments. In such scenarios, the identification and surgical exploration of radioactive fragments is a major issue to prevent further radiation-induced effects like wound healing disorders, onset of acute radiation syndrome, and as a late-effect cancer. However, in a usual emergency setting, it is unclear how this task can be achieved. Within this study, we evaluated the feasibility of different radiological methods to identify and locate an incorporated radioactive fragment. We placed two different Cs sources and several non-radioactive fragments representing sham control samples within a human spine phantom. Standard emergency imaging procedures were performed, including plane radiography and different CT scans (64 row, 384 row dual energy, 320 row without iterative metal artifact reduction), respectively. Eight radiologists were blinded toward the results and asked to identify the radioactive fragments within the provided images. For both sources, correct identification was rather low (15.63%). Furthermore, none of the questioned radiologists (N = 0) stated that they were able to identify the radioactive shrapnel distinctly. Positive predictive value was accordingly low (15.63%). Most participants recommended a scintigraphy-based technique for identification (26.67%) rather than radiographic procedures (6.67%). Identification and location of incorporated small radioactive fragments with low energies by standard radiological procedures prior to surgical exploration is not promising. Nevertheless, procedures that can achieve this aim are needed direly in the case of a terrorist attack with a radiological dispersal device and should be available in an emergency department.

X-ray irradiation induces subtle changes in the genome-wide distribution of DNA hydroxymethylation with opposing trends in genic and intergenic regions.

DNA hydroxymethylation has gained attention as an intermediate in the process of DNA demethylation. More recently, 5-hydroxymethylcytosine has been recognized as an independent epigenetic mark that can persist over time and that exerts influence on gene regulation and other biological processes. Deregulation of this DNA modification has been linked to tumorigenesis and a variety of other diseases. The impact of irradiation on DNA hydroxymethylation is poorly understood. In this study we exposed lung fibroblasts (IMR90) to 0.5 Gy and 2 Gy of X-rays, respectively. We characterized radiation induced changes of DNA hydroxymethylation 1 h, 6 h, 24 h and 120 h after exposure employing immunoprecipitation and subsequent deep sequencing of the genomic fraction enriched for hydroxymethylated DNA. Transcriptomic response to irradiation was analyzed for time points 6 h and 24 h post exposure by means of RNA sequencing. Irradiated and sham-irradiated samples shared the same overall distribution of 5-hydroxymethylcytosines with respect to genomic features such as promoters and exons. The frequency of 5-hydroxymethylcytosine peaks differentially detected in irradiated samples increased in genic regions over time, while the opposing trend was observed for intergenic regions. Onset and extent of this effect was dose dependent. Moreover, we demonstrated a biased distribution of 5-hmC alterations at CpG islands and sites occupied by the DNA binding protein CTCF. In summary, our study provides new insights into the epigenetic response to irradiation. Our data highlight genomic features more prone to irradiation induced changes of DNA hydroxymethylation, which might impact early and late onset effects of irradiation.

Gene expression changes in human iPSC-derived cardiomyocytes after X-ray irradiation.

Purpose: Radiation-induced heart disease caused by cardiac exposure to ionizing radiation comprises a variety of cardiovascular effects. Research in this field has been hampered by limited availability of clinical samples and appropriate test models. In this study, we wanted to elucidate the molecular mechanisms underlying electrophysiological changes, which we have observed in a previous study. Materials and methods: We employed RNA deep-sequencing of human-induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) 48 h after 5 Gy X-ray irradiation. By comparison to public data from hiPSC-CMs and human myocardium, we verified the expression of cardiac-specific genes in hiPSC-CMs. Results were validated by qRT-PCR. Results: Differentially gene expression analysis identified 39 and 481 significantly up- and down-regulated genes after irradiation, respectively. Besides, a large fraction of genes associated with cell cycle processes, we identified genes implicated in cardiac calcium homeostasis (PDE3B), oxidative stress response (FDXR and SPATA18) and the etiology of cardiomyopathy (SGCD, BBC3 and GDF15). Conclusions: Notably, observed gene expression characteristics specific to hiPSC-CMs might be relevant regarding further investigations of the response to external stressors like radiation. The genes and biological processes highlighted in our study present promising starting points for functional follow-up studies for which hiPSC-CMs could pose an appropriate cell model when cell type specific peculiarities are taken into account.

Genome-Wide Analysis of Interchromosomal Interaction Probabilities Reveals Chained Translocations and Overrepresentation of Translocation Breakpoints in Genes in a Cutaneous T-Cell Lymphoma Cell Line.

In classical models of tumorigenesis, the accumulation of tumor promoting chromosomal aberrations is described as a gradual process. Next-generation sequencing-based methods have recently revealed complex patterns of chromosomal aberrations, which are beyond explanation by these classical models of karyotypic evolution of tumor genomes. Thus, the term chromothripsis has been introduced to describe a phenomenon, where temporarily and spatially confined genomic instability results in dramatic chromosomal rearrangements limited to segments of one or a few chromosomes. Simultaneously arising and misrepaired DNA double-strand breaks are also the cause of another phenomenon called chromoplexy, which is characterized by the presence of chained translocations and interlinking deletion bridges involving several chromosomes. In this study, we demonstrate the genome-wide identification of chromosomal translocations based on the analysis of translocation-associated changes in spatial proximities of chromosome territories on the example of the cutaneous T-cell lymphoma cell line Se-Ax. We have used alterations of intra- and interchromosomal interaction probabilities as detected by genome-wide chromosome conformation capture (Hi-C) to infer the presence of translocations and to fine-map their breakpoints. The outcome of this analysis was subsequently compared to datasets on DNA copy number alterations and gene expression. The presence of chained translocations within the Se-Ax genome, partly connected by intervening deletion bridges, indicates a role of chromoplexy in the etiology of this cutaneous T-cell lymphoma. Notably, translocation breakpoints were significantly overrepresented in genes, which highlight gene-associated biological processes like transcription or other gene characteristics as a possible cause of the observed complex rearrangements. Given the relevance of chromosomal aberrations for basic and translational research, genome-wide high-resolution analysis of structural chromosomal aberrations will gain increasing importance.

Impact of Ionizing Radiation on Electrophysiological Behavior of Human-induced Ipsc-derived Cardiomyocytes on Multielectrode Arrays.

Cardiac arrhythmia presumably induced through cardiac fibrosis is a recurrent long-term consequence of exposure to ionizing radiation. However, there is also evidence that cardiac arrhythmia can occur in patients shortly after irradiation. In this study, the authors employed multielectrode arrays to investigate the short-term effects of x-ray radiation on the electrophysiological behavior of cardiomyocytes derived from human-induced pluripotent stem cells. These cardiomyocytes with spontaneous pacemaker activity were cultured on single-well multielectrode arrays. After exposure to 0, 0.5, 1, 2, 5, 10 Gy x-ray radiation, electrical activity was measured at time points ranging from 10 min to 96 h. RNA sequencing was employed to verify the expression of genes specifically involved in cardiomyocyte differentiation and function. A decrease in beating rate was observed after irradiation with 5 and 10 Gy starting 48 h after exposure. Cells exposed to higher doses of radiation were more prone to show changes in electrophysiological spatial distribution. No radiation-induced effects with respect to the corrected QT interval were detectable. Gene expression analysis showed up regulation of typical cardiac features like ACTC1 or HCN4. In this study, early dose-dependent changes in electrophysiological behavior were determined after x-ray irradiation. Results point towards a dose-dependent effect on pacemaker function of cardiomyocytes and indicate a possible connection between irradiation and short-term changes in electrophysiological cardiac function. Cardiomyocytes derived from human-induced pluripotent stem cells on multielectrode arrays represent a promising in vitro cardiac-modeling system for preclinical studies.

Exploring the Link between Radiation Exposure and Multifocal Basal Cell Carcinomas in a Former Chernobyl Clean-up Worker by Combining Different Molecular Biological Techniques.

Thirty years after the Chernobyl nuclear power plant accident we report on a patient who was a clean-up worker, who subsequently developed multiple cutaneous basal cell carcinomas (BCCs). We used several methods to assess the biological long-term effects related to low-dose external and internal radiation exposure. Specifically, because BCC risk may be increased with ionizing radiation exposure, we endeavored to determine whether the multifocal BCCs were related to the patient's past clean-up work. We assessed cytogenetic changes using peripheral blood, and internal incorporation was measured with a whole-body counter. Gene expression alterations were determined and array-based comparative genomic hybridization was performed for copy number aberration analysis of available BCC samples. In 1,053 metaphase cells, the dicentric yield of 0.005 dicentrics, with acentrics/cell, was significantly increased compared to the established calibration curve (P < 0.001). A 2.5-fold increase in total translocations was observed compared to the expected translocation rate. No internal contamination was detected with the whole-body counter. At the RNA level, two of seven genes (HNRNPA1, AGAP4/6/8) indicated internal plutonium exposure associated with the lowest dose category found in Mayak workers (>0-0.055 Gy). Relevant DNA copy number changes were only detected within the most aggressive BCC focus. Our results suggest that the examined worker had low and more recent radiation exposure with presumably internalized radionuclides that were below the detection level of a whole-body counter. The multifocal BCC could not be related to past occupational radiation exposure. The findings from our study suggest that integrating different methodologies potentially provides an improved overall assessment of individual health risks associated with or excluding occupational radiation exposure.

Cognitive trajectory after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is known to be associated with silent cerebral injury, which could contribute to cognitive impairment. Considering its increasing use, thorough longitudinal investigation of cognitive trajectory after TAVI is pivotal. METHODS AND RESULTS: Repeatable battery for the assessment of neuropsychological status was performed before (E1), 3 days (E2), 3 months (E3), 1 (E4) year, and 2 years (E5) after TAVI. Baseline characteristics, procedural data, imaging parameters of brain injury (diffusion-weighted MRI), and the use of conceivable neuroprotective approaches were investigated for their effect on cognitive function. Cognitive performance was investigated in 111 patients (mean log EuroSCORE, 30±13%). Global cognitive function (repeatable battery for the assessment of neuropsychological status total score) increased transiently at E2 (P=0.02) and was comparable with baseline levels at E3, E4, and E5. Six patients (5.4%) demonstrated early cognitive decline. Persistence and late onset were seen infrequently (n=3, 2.7% and n=4, 3.6%, respectively). Hence, early cognitive decline was ruled out in 105 patients (94.6%), and a majority of patients (91%) demonstrated sustained cognitive performance throughout all investigated time points. Interestingly, only patient age (P=0.012), but not prior cerebrovascular events, cognitive status, direct TAVI, cerebral embolism in diffusion-weighted MRI, or the use of a cerebral embolic protection device was found to be independently associated with cognitive decline, linking higher age to cognitive impairment along the first 2 years after TAVI. CONCLUSIONS: Long-term cognitive performance was preserved in the great majority (91%) of patients throughout the first 2 years after TAVI, despite the high intrinsic risk for cognitive deterioration. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883285.

Prognostic value of cerebral injury following transfemoral aortic valve implantation.

AIMS: To evaluate the impact of serological, imaging and clinical measures of cerebral injury on patient self-sufficiency and survival after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Before and three days after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological performance utilising National Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was determined with established score systems (instrumental activities of daily living score, Barthel Index). Parameters of cerebral injury were investigated for their impact on self-sufficiency and all-cause mortality after 30 days and one year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4±18.1, STS score: 7.9±5.7), of whom 39 completed the imaging protocol. The incidences of NSE increase, new embolic events in DW-MRI, and neurological deficit early after TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant comorbidities, reflected by higher risk scores, had significant impact on outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to self-sufficiency nor to survival one year after TAVI. CONCLUSIONS: In this observational pilot study, "silent" cerebral injury is neither related to dependent lifestyle nor to mortality during the first year after TAVI. However, long-term follow-up is needed to elucidate fully the impact of silent stroke. Clinical trials number: NCT00883285.

Prognostic value of cerebral injury following transfemoral aortic valve implantation.

Aims: To evaluate the impact of serological, imaging and clinical measures of cerebral injury on patient self-sufficiency and survival after transcatheter aortic valve implantation (TAVI). Methods and results: Before and three days after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological performance utilising National Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was determined with established score systems (instrumental activities of daily living score, Barthel Index). Parameters of cerebral injury were investigated for their impact on self-sufficiency and all-cause mortality after 30 days and one year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4±18.1, STS score: 7.9±5.7), of whom 39 completed the imaging protocol. The incidences of NSE increase, new embolic events in DW-MRI, and neurological deficit early after TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant comorbidities, reflected by higher risk scores, had significant impact on outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to self-sufficiency nor to survival one year after TAVI. Conclusions: In this observational pilot study, "silent" cerebral injury is neither related to dependent lifestyle nor to mortality during the first year after TAVI. However, long-term follow-up is needed to elucidate fully the impact of silent stroke. Clinical trials number: NCT00883285.