CCL18, CHI3L1, ANG2, IL-6 systemic levels are associated with the extent of lung damage and radiomic features in SARS-CoV-2 infection.

OBJECTIVE AND DESIGN: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. MATERIAL OR SUBJECTS: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. METHODS: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. RESULTS: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. CONCLUSION: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes.

Smart probes for optical imaging of T cells and screening of anti-cancer immunotherapies.

T cells are an essential part of the immune system with crucial roles in adaptive response and the maintenance of tissue homeostasis. Depending on their microenvironment, T cells can be differentiated into multiple states with distinct functions. This myriad of cellular activities have prompted the development of numerous smart probes, ranging from small molecule fluorophores to nanoconstructs with variable molecular architectures and fluorescence emission mechanisms. In this Tutorial Review, we summarize recent efforts in the design, synthesis and application of smart probes for imaging T cells in tumors and inflammation sites by targeting metabolic and enzymatic biomarkers as well as specific surface receptors. Finally, we briefly review current strategies for how smart probes are employed to monitor the response of T cells to anti-cancer immunotherapies. We hope that this Review may help chemists, biologists and immunologists to design the next generation of molecular imaging probes for T cells and anti-cancer immunotherapies.

Site-Specific Chemical Modification of a Cytokine Mimic for Small Molecule-Based Tumor Targeting.

The targeted delivery of bioactive proteins, such as cytokines, for cancer immunotherapy approaches mostly relies on antibodies or antibody fragments. However, fusion proteins may display low tissue penetration due to a large molecular size. Small molecule ligands with high affinity toward tumor-associated antigens provide a promising alternative for the selective delivery of cytokines to tumor lesions. We developed a one-pot procedure for the site-specific thiazolidine formation between an aldehyde bearing small molecule and the in situ generated N-terminal cysteine of a bioactive protein. Thereby, neoleukin-2/15 (Neo-2/15), a computationally engineered interleukin-2 and -15 mimic, was chemically conjugated to acetazolamide plus, a potent carbonic anhydrase IX (CAIX) ligand. The conjugate retained the biological activity of Neo-2/15 and revealed its ability to accumulate in renal cell carcinoma (SK-RC-52) xenografts upon systemic intravenous administration. The results highlight the potential of small molecule targeting moieties to drive the accumulation of a protein cargo to the respective disease site while conserving the small construct size.

Enzyme-Activatable Chemokine Conjugates for In Vivo Targeting of Tumor-Associated Macrophages.

Increased levels of tumor-associated macrophages (TAMs) are indicators of poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment of macrophages to tumors are under evaluation as anticancer therapies, these strategies are not specific for macrophage subpopulations. Herein we report the first enzyme-activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors. Our constructs exploit the high expression of chemokine receptors (e.g., CCR2) and the activity of cysteine cathepsins in TAMs to target these cells selectively over other macrophages and immune cells (e.g., neutrophils, T cells, B cells). Furthermore, we demonstrate that cathepsin-activatable chemokines are compatible with both fluorescent and therapeutic cargos, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.

Cone beam CT augmented fluoroscopy allows safe and efficient diagnosis of a difficult lung nodule.

BACKGROUND: Detection of small peripheral lung nodules is constantly increasing with the development of low dose computed tomography lung cancer screening programs. A tissue diagnosis is often required to confirm malignity, with endobronchial biopsies being associated with a lower pneumothorax rate than percutaneous approaches. Endoscopic diagnosis of peripheral small size lung nodules is however often challenging using traditional bronchoscopy and endobronchial ultrasound alone. New virtual bronchoscopic navigation techniques such as electromagnetic navigational bronchoscopy (ENB) have developed to improve peripheral navigation, with diagnostic yield however remaining in the 30-50% range for small lesions. Recent studies have shown the benefits of combining Cone beam computed tomography (CBCT) with ENB to improve diagnostic yield to up to 83%. The use of ENB however remains limited by disposable cost, bronchus sign dependency and inaccuracies due to CT to body divergence. CASE PRESENTATION: This case report highlights the feasibility and usefulness of CBCT-guided bronchoscopy for the sampling of lung nodules difficult to reach through traditional bronchoscopy because of nodule size and peripheral position. Procedure was scheduled in a mobile robotic hybrid operating room with patient under general anaesthesia. CBCT acquisition was performed to localize the target lesion and plan the best path to reach it into bronchial tree. A dedicated software was used to segment the lesion and the bronchial path which 3D outlines were automatically fused in real time on the fluoroscopic images to augment live guidance. Navigation to the lesion was guided with bronchoscopy and augmented fluoroscopy alone. Before the sampling, CBCT imaging was repeated to confirm the proper position of the instrument into the lesion. Four transbronchial needle aspirations (TBNA) were performed and the tissue analysis showed a primary lung adenocarcinoma. CONCLUSIONS: CBCT and augmented fluoroscopy technique is a safe and effective and has potential to improve early stage peripheral lesions endobronchial diagnostic yield without ENB. Additional studies are warranted to confirm its safety, efficacy and technical benefits, both for diagnosis of oncological and non-oncological disease and for endobronchial treatment of inoperable patients.

How direct measurements of worker eyes with a Scheimpflug camera can affect lensdose coefficients in interventional radiology.

The 2013/59/Euratom Directive reduced the occupational exposure limits for the lens. Since it has become crucial to estimate the dose absorbed by the lens, we have studied the individual variability of exposed workers' ocular conformations with respect to the data estimated from their personal dosimetry. The anterior eye conformations of 45 exposed workers were acquired using Scheimpflug imaging and classified according to their sight conditions (emmetropia, myopia or hypermetropia). Three eye models were computed, with two lens reconstructions, and implemented in an interventional radiology scenario using Monte Carlo code. The models were dosimetrically analysed by simulating setup A, a theoretical monoenergetic and isotropic photon source (10-150 keV) and setup B, a more realistic interventional setting with an angiographic x-ray unit (50, 75, 100 kV peak). Scheimpflug imaging provided an average anterior chamber depth of (6.4 ± 0.5) mm and a lens depth of (3.9 ± 0.3) mm, together with a reconstructed equatorial lens length of (7.1-10.1) mm. Using these data for model reconstruction, dose coefficients (DCs) were simulated for all ocular structures. Regardless of the eye model used, the DCs showed a similar trend with radiation energy, which highlighted that for the same energy and setup, no significant dependence on ocular morphology and workers' visual conditions was observed. The maximum difference obtained did not exceed 1% for all eye models or structures analysed. Therefore, the individual variabilities of worker ocular anatomy do not require any additional correction, compared to the personal dosimetry data measured with a dedicated lens dosimeter. To estimate the dose absorbed by the other eye structures, it is, instead, essential to know the spectrum of the source that has generated the irradiation, since there are differences between monoenergetic sources and more realistic angiographic units.

Comparing two visualization protocols for tomosynthesis in screening: specificity and sensitivity of slabs versus planes plus slabs.

OBJECTIVES: Tomosynthesis (DBT) has proven to be more sensitive than digital mammography, but it requires longer reading time. We retrospectively compared accuracy and reading times of a simplified protocol with 1-cm-thick slabs versus a standard protocol of slabs + 1-mm-spaced planes, both integrated with synthetic 2D. METHODS: We randomly selected 894 DBTs (including 12 cancers) from the experimental arm of the RETomo trial. DBTs were read by two radiologists to estimate specificity. A second set of 24 cancers (8 also present in the first set) mixed within 276 negative DBTs was read by two radiologists. In total, 28 cancers with 64 readings were used to estimate sensitivity. Radiologists read with both protocols separated by a 3-month washout. Only women that were positive at the screening reading were assessed. Variance was estimated taking into account repeated measures. RESULTS: Sensitivity was 82.8% (53/64, 95% confidence interval (95% CI) 67.2-92.2) and 90.6% (95% CI 80.2-95.8) with simplified and standard protocols, respectively. In the random screening setting, specificity was 97.9% (1727/1764, 95% CI 97.1-98.5) and 96.3% (95% CI 95.3-97.1), respectively. Inter-reader agreement was 0.68 and 0.54 with simplified and standard protocols, respectively. Median reading times with simplified protocol were 20% to 30% shorter than with standard protocol. CONCLUSIONS: A simplified protocol reduced reading time and false positives but may have a negative impact on sensitivity. KEY POINTS: • The adoption of digital breast tomosynthesis (DBT) in screening, more sensitive than mammography, could be limited by its potential effect on the radiologists' workload, i.e., increased reading time and fatigue. • A DBT simplified protocol with slab only, compared to a standard protocol (slab plus planes) both integrated with synthetic 2D, reduced time and false positives but had a negative impact on sensitivity.

RIS-PACS, patient safety, and clinical risk management.

PURPOSE: Clinical risk management is the basis of safety procedures also in radiological workflows. In the literature, it has been documented that the incidence of reconciled radiological studies ranges between 0.2 and 0.5 % of stored studies, a non-negligible value if we consider the high number of diagnostic tests performed. MATERIALS AND METHODS: In radiology, "non-compliance" or, more generally, data to be reconciled means any circumstance in which wrong information is recorded in RIS and/or PACS, which requires processing to amend or correct images, reports or other information in order to attribute them to the right patient/episode. Non-compliance corrections account for almost 50 % of the medical system administrator's (SA) workload. This paper describes how the Reggio Emilia Province Diagnostic Imaging and Laboratory Medicine Department manages risk in clinical radiology, in compliance with Regional indications on RIS-PACS safety. A dedicated RIS webpage has been developed in order to manage reconciliation requests. Native integration with PACS makes information about ongoing reconciliations available to anyone who consults the images. RESULTS: In 2013, non-compliances reported by radiology staff ranged between 0.25 and 0.35 % of studies sent to the PACS. More than 50 % of non-compliances can be related to high clinical risk, which requires implementation of efficient and effective rapid mechanisms of action-reaction inside and outside the radiology department. CONCLUSIONS: The RIS-integrated module has been the starting point for managing and monitoring errors, allowing improvement initiatives to guarantee and optimise workflow. Request and event traceability have allowed us to define personalised training programmes, designed to minimise procedural and/or systematic errors. To protect the availability and consistency of information produced by radiology units, it is necessary to provide integrated and effective mechanisms for reconciliation management. The integrated tool described in this paper is now widely used (not only by our centre): radiographers and radiologists can indicate non-compliances in an efficient and effective manner, informing all the operators involved with just a click of the mouse. Similar functionality should be implemented in the next generation of RIS-PACS in order to maintain the highest possible safety level for patients and workers.

Physical and dosimetric characterisation of different Contrast-Enhanced digital mammographic systems: A multicentric study.

PURPOSE: Contrast-enhanced digital mammography (CEDM) is a relatively new imaging technique recombining low- and high-energy mammograms to emphasise iodine contrast. This work aims to perform a multicentric physical and dosimetric characterisation of four state-of-the-art CEDM systems. METHODS: We evaluated tube output, half-value-layer (HVL) for low- and high-energy and average glandular dose (AGD) in a wide range of equivalent breast thicknesses. CIRS phantom 022 was used to estimate the overall performance of a CEDM examination in the subtracted image in terms of the iodine difference signal (S). To calculate dosimetric impact of CEDM examination, we collected 4542 acquisitions on patients. RESULTS: Even if CEDM acquisition strategies differ, all the systems presented a linear behaviour between S and iodine concentration. The curve fit slopes expressed in PV/mg/cm2 were in the range [92-97] for Fujifilm, [31-32] for GE Healthcare, [35-36] for Hologic, and [114-130] for IMS. Dosimetric data from patients were matched with AGD values calculated using equivalent PMMA thicknesses. Fujifilm exhibited the lowest values, while GE Healthcare showed the highest. CONCLUSION: The subtracted image showed the ability of all the systems to give important information about the linearity of the signal with the iodine concentrations. All the patient-collected doses were under the AGD EUREF 2D Acceptable limit, except for patients with thicknesses ≤35 mm belonging to GE Healthcare and Hologic, which were slightly over. This work demonstrates the importance of testing each CEDM system to know how it performs regarding dose and the relationship between PV and iodine concentration.

Nonperturbative Fluorogenic Labeling of Immunophilins Enables the Wash-free Detection of Immunosuppressants.

Immunosuppressants are clinically approved drugs to treat the potential rejection of transplanted organs and require frequent monitoring due to their narrow therapeutic window. Immunophilins are small proteins that bind immunosuppressants with high affinity, yet there are no examples of fluorogenic immunophilins and their potential application as optical biosensors for immunosuppressive drugs in clinical biosamples. In the present work, we designed novel diazonium BODIPY salts for the site-specific labeling of tyrosine residues in peptides via solid-phase synthesis as well as for late-stage functionalization of whole recombinant proteins. After the optimization of a straightforward one-step labeling procedure for immunophilins PPIA and FKBP12, we demonstrated the application of a fluorogenic analogue of FKBP12 for the selective detection of the immunosuppressant drug tacrolimus, including experiments in urine samples from patients with functioning renal transplants. This chemical methodology opens new avenues to rationally design wash-free immunophilin-based biosensors for rapid therapeutic drug monitoring.

Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

Efficiency and effectiveness of an innovative RIS function for patient information reconciliation directly integrated with PACS.

In RIS-PACS systems, potential errors occurring during the execution of a radiologic examination can amplify the clinical risks of the patient during subsequent treatments, e.g., of oncologic patients or of those who must do additional treatments based on the initial diagnosis. In Reggio Emilia Province Diagnostic Imaging Department (REDID) we experienced different strategies to reduce clinical risks due to patient reconciliation errors. In 2010, we developed a procedure directly integrated in our RIS-PACS that uses Health Level 7 (HL7) standard messaging, which generates an overlay with the text "under investigation" on the images of the study to be corrected. All the healthcare staff is informed of the meaning of that overlay, and only the radiologist and the emergency services staff can consult these images on PACS. The elimination of image overlay and of any access limitation to PACS was triggered to confirm of the right correction made by RIS-PACS system administrator (SA). The RIS-PACS integrated tool described in this paper allows technologists and radiologists to efficiently highlight patient exam errors and to inform all the users to minimize the overall clinical risks, with a significant savings in costs. Over the years, we have observed a steady decrease in the percentage of reconciled studies. Error reconciliation requires an effective and efficient mechanism. The RIS-PACS integrated tool described in this paper enables technologists and radiologists to quickly and efficiently highlight patient exam errors and inform all the users. Next generation of RIS-PACS could be equipped with similar reconciliation tools.

Lung dual energy CT: Impact of different technological solutions on quantitative analysis.

PURPOSE: To evaluated the accuracy of spectral parameters quantification of four different CT scanners in dual energy examinations of the lung using a dedicated phantom. METHOD: Measurements were made with different technologies of the same vendor: one dual source CT scanner (DSCT), one TwinBeam (i.e. split filter) and two sequential acquisition single source scanners (SSCT). Angular separation of Calcium and Iodine signals were calculated from scatter plots of low-kVp versus high-kVp HUs. Electron density (ρe), effective atomic number (Zeff) and Iodine concentration (Iconc) were measured using Syngo.via software. Accuracy (A) of ρe, Zeff and Iconc was evaluated as the absolute percentage difference (D%) between reference values and measured ones, while precision (P) was evaluated as the variability σ obtained by repeating the measurement with different acquisition/reconstruction settings. RESULTS: Angular separation was significantly larger for DSCT (α = 9.7°) and for sequential SSCT (α = 9.9°) systems. TwinBeam was less performing in material separation (α = 5.0°). The lowest average A was observed for TwinBeam (Aρe = [4.7 ± 1.0], AZ = [9.1 ± 3.1], AIconc = [19.4 ± 4.4]), while the best average A was obtained for Flash (Aρe = [1.8 ± 0.4], AZ = [3.5 ± 0.7], AIconc = [7.3 ± 1.8]). TwinBeam presented inferior average P (Pρe = [0.6 ± 0.1], PZ = [1.1 ± 0.2], PIconc = [10.9 ± 4.9]), while other technologies demonstrate a comparable average. CONCLUSIONS: Different technologies performed material separation and spectral parameter quantification with different degrees of accuracy and precision. DSCT performed better while TwinBeam demonstrated not excellent performance. Iodine concentration measurements exhibited high variability due to low Iodine absolute content in lung nodules, thus limiting its clinical usefulness in pulmonary applications.

Artificial Intelligence-Assisted Processing of Anterior Segment OCT Images in the Diagnosis of Vitreoretinal Lymphoma.

Anterior segment optical coherence tomography (AS-OCT) allows the explore not only the anterior chamber but also the front part of the vitreous cavity. Our cross-sectional single-centre study investigated whether AS-OCT can distinguish between vitreous involvement due to vitreoretinal lymphoma (VRL) and vitritis in uveitis. We studied AS-OCT images from 28 patients (11 with biopsy-proven VRL and 17 with differential diagnosis uveitis) using publicly available radiomics software written in MATLAB. Patients were divided into two balanced groups: training and testing. Overall, 3260/3705 (88%) AS-OCT images met our defined quality criteria, making them eligible for analysis. We studied five different sets of grey-level samplings (16, 32, 64, 128, and 256 levels), finding that 128 grey levels performed the best. We selected the five most effective radiomic features ranked by the ability to predict the class (VRL or uveitis). We built a classification model using the xgboost python function; through our model, 87% of eyes were correctly diagnosed as VRL or uveitis, regardless of exam technique or lens status. Areas under the receiver operating characteristic curves (AUC) in the 128 grey-level model were 0.95 [CI 0.94, 0.96] and 0.84 for training and testing datasets, respectively. This preliminary retrospective study highlights how AS-OCT can support ophthalmologists when there is clinical suspicion of VRL.

A comparison of digital radiography systems in terms of effective detective quantum efficiency.

PURPOSE: The purpose of this study is to compare digital radiography systems using the metric effective detective quantum efficiency (eDQE), which better reflects digital radiography imaging system performance under clinical operating conditions, in comparison with conventional metrics such as modulation transfer function (MTF), normalized noise power spectra (NNPS), and detective quantum efficiency (DQE). METHODS: The eDQE was computed by the calculation of the MTF, the NNPS, the phantom attenuation and scatter, and estimation of x-ray flux. The physical characterization of the systems was obtained with the standard beam conditions RQA5 and RQA9, using the PA Chest phantom proposed by AAPM Report # 31 simulating the attenuation and scatter characteristics of the adult human thorax. The MTF (eMTF) was measured by using an edge test placed at the frontal surface of the phantom, the NNPS (eNNPS) was calculated from images of the phantom acquired at three different exposure levels covering the operating range of the system (E(0), which is the exposure at which a system is normally operated, 1/3 E(0), and 3 E0), and scatter measurements were assessed by using a beam-stop technique. The integral of DQE (IDQE) and eDQE (IeDQE) was calculated over the whole spatial frequency range. RESULTS: The eMTF results demonstrate degradation due to magnification and the presence of scattered radiation. The eNNPS was influenced by the grid presence, and in some systems, it contained structured noise. At typical clinical exposure levels, the magnitude of eDQE(0) with respect to DQE(0) at RQA9 beam conditions was 13%, 17%, 16%, 36%, and 24%, respectively, for Carestream DRX-1, Carestream DRX-1C, Carestream Direct View CR975, Philips Digital Diagnost VM, and GE Revolution XR/d. These results were confirmed by the ratio of IeDQE and IDQE in the same conditions. CONCLUSIONS: The authors confirm the robustness and reproducibility of the eDQE method. As expected, the DR systems performed better than the CR systems due to their superior signal-to-noise transfer characteristics. The results of this study suggest the eDQE method may provide an opportunity to more accurately assess the clinical performance of digital radiographic imaging systems by accounting for factors such as the presence of scatter, use of an antiscatter grid, and magnification and focal spot blurring effects, which are not reflected in conventional DQE measures.

A Fast and Interpretable Deep Learning Approach for Accurate Electrostatics-Driven pKa Predictions in Proteins.

Existing computational methods for estimating pKa values in proteins rely on theoretical approximations and lengthy computations. In this work, we use a data set of 6 million theoretically determined pKa shifts to train deep learning models, which are shown to rival the physics-based predictors. These neural networks managed to infer the electrostatic contributions of different chemical groups and learned the importance of solvent exposure and close interactions, including hydrogen bonds. Although trained only using theoretical data, our pKAI+ model displayed the best accuracy in a test set of ∼750 experimental values. Inference times allow speedups of more than 1000× compared to physics-based methods. By combining speed, accuracy, and a reasonable understanding of the underlying physics, our models provide a game-changing solution for fast estimations of macroscopic pKa values from ensembles of microscopic values as well as for many downstream applications such as molecular docking and constant-pH molecular dynamics simulations.

Enzyme-Activatable Chemokine Conjugates for In Vivo Targeting of Tumor-Associated Macrophages.

Increased levels of tumor-associated macrophages (TAMs) are indicators of poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment of macrophages to tumors are under evaluation as anticancer therapies, these strategies are not specific for macrophage subpopulations. Herein we report the first enzyme-activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors. Our constructs exploit the high expression of chemokine receptors (e.g., CCR2) and the activity of cysteine cathepsins in TAMs to target these cells selectively over other macrophages and immune cells (e.g., neutrophils, T cells, B cells). Furthermore, we demonstrate that cathepsin-activatable chemokines are compatible with both fluorescent and therapeutic cargos, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.

Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer.

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.

Empirical modeling and simulation of phase noise in long-haul coherent optical transmission systems.

An empirical phase noise channel model suitable for performance evaluation of high spectrally efficient modulations in 100G long-haul coherent optical transmission systems using polarization-division multiplexed and wavelength-division multiplexing channels is presented. The derivation of the model is worked out by exploiting the similarity between the power spectral density of the carrier extracted from the analysis of propagation measurements and the Lorentzian spectrum that is usually adopted to describe instabilities of semiconductor lasers. The proposed channel model is characterized by only two parameters: the linewidth of the carrier and the signal-to-noise ratio. We show that in the case of quadrature phase-shift keying transmission a good agreement exists between quantitative measures of performance extracted by processing experimental data and those obtained from simulations based on the use of the empirical model.