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The purpose of this study was to investigate the effect of image preprocessing on radiomic features estimation from computed tomography (CT) imaging of locally advanced rectal cancer (LARC). CT images of 20 patients with LARC were used to estimate 105 radiomic features of 7 classes (shape, first-order, GLCM, GLDM, GLRLM, GLSZM, and NGTDM). Radiomic features were estimated for 6 different isotropic resampling voxel sizes, using 10 interpolation algorithms (at fixed bin width) and 6 different bin widths (at fixed interpolation algorithm). The intraclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated to assess the variability in radiomic features estimation due to preprocessing. A repeated measures correlation analysis was performed to assess any linear correlation between radiomic feature estimate and resampling voxel size or bin width. Reproducibility of radiomic feature estimate, when assessed through ICC analysis, was nominally excellent ( ICC > 0.9 ) for shape features, good ( 0.75 < ICC ≤ 0.9 ) or moderate ( 0.5 < ICC ≤ 0.75 ) for first-order features, and moderate or poor ( 0 ≤ ICC ≤ 0.5 ) for textural features. A number of radiomic features characterized by good or excellent reproducibility in terms of ICC showed however median CV values greater than 15%. For most textural features, a significant ( p < 0.05 ) correlation between their estimate and resampling voxel size or bin width was found. In CT imaging of patients with LARC, the estimate of textural features, as well as of first-order features to a lesser extent, is appreciably biased by preprocessing. Accordingly, this should be taken into account when planning clinical or research studies, as well as when comparing results from different studies and performing multicenter studies.

Pancreatic cancer has a poor prognosis due to its aggressive nature and ability to metastasize at an early stage. Currently, its management is still a challenge because this neoplasm is resistant to conventional treatment approaches, among which is chemo-radiotherapy (CRT), due to the abundant stromal compartment involved in the mechanism of hypoxia. Hyperthermia, among other effects, counteracts hypoxia by promoting blood perfusion and thereby can enhance the therapeutic effect of radiotherapy (RT). Therefore, the establishment of integrated treatments would be a promising strategy for the management of pancreatic carcinoma. Here, the effects of joint radiotherapy/hyperthermia (RT/HT) on optimized chick embryo chorioallantoic membrane (CAM) pancreatic tumor models are investigated. This model enables a thorough assessment of the tumor-arresting effect of the combined approach as well as the quantitative evaluation of hypoxia and cell cycle-associated mechanisms by both gene expression analysis and histology. The analysis of the lower CAM allows to investigate the variation of the metastatic behaviors of the cancer cells associated with the treatments. Overall, this study provides a potentially effective combined strategy for the non-invasive management of pancreatic carcinoma.

Radiotherapy (RT) is a fundamental tool in cancer treatment. Recent technological advances improved considerably radiotherapy techniques, allowing to obtain more precise, effective and most importantly safer treatments. However, RT is not without risks. Ionizing radiation also injures healthy cells, and there is a limit to the amount of radiation an area of the body can safely receive over the course of a lifetime. A new delivery method, called FLASH radiotherapy (FLASH-RT) has shown very promising results in in vivo studies, where a significant increase in healthy tissue sparing (FLASH effect) was observed. FLASH-RT consists in delivering the ionizing radiation therapy at dose rates much higher than the ones used in conventional radiotherapy (CONV-RT). Because of the novelty of this method, every aspect of FLASH-RT is under study, such as how the FLASH effect depends on therapy delivery parameters and what exactly are the underlining biological mechanisms. Nonetheless, dosimetry presents a challenge to overcome. The high dose rates cause significant saturation problems which render standard dosimetric equipment inadequate. Therefore, the development of online (active) dosimeters is a priority. In the short term this technology enables more efficient measurements in the experimental context, since it gives immediate feedback. In the long term it provides the basis for future studies on dosimetry in clinical practice. In this work we show the construction and characterization of online FLASH dosimeters based on scintillator materials used in integrating-mode. A GEANT4 based Monte Carlo simulation code is specifically developed to calculate the medium-equivalence correction. The simulation is validated with experimental measurements obtained with a full-fledged FLASH linear accelerator, which produces electron pulsed beams at very high dose per pulse. Measurements suggest that the proposed dosimeters have a linear response in a wide range of dose per pulse values up to 6 Gy/p, while moderate saturation can be observed up to 12.5 Gy/p.

Ultra-High dose -per-pulse regimens (UHDP), necessary to trigger the "FLASH" effect, still pose serious challenges to dosimetry. Dosimetry plays a crucial role, both to significantly improve the accuracy of the radiobiological experiments necessary to fully understand the mechanisms underlying the effect and its dependencies on the beam parameters, and to be able to translate such effect into clinical practice. The standard ionization chamber in UHDP region is significantly affected by the effects of the electric field generated by the enormous density of charges produced by the dose pulse.This work describes the theory and the conceptual design of a gas chamber (the ALLS chamber) which overcomes the above-mentioned problems.

Background: A fair amount of microcalcifications sent for biopsy are false positives. The study investigates whether quantitative radiomic features extracted from digital breast tomosynthesis (DBT) can be an additional and useful tool to discriminate between benign and malignant BI-RADS category 4 microcalcification. Methods: This retrospective study included 252 female patients with BI-RADS category 4 microcalcifications. The patients were divided into two groups according to micro-histopathology: 126 patients with benign lesions and 126 patients with certain or possible malignancies. A total of 91 radiomic features were extracted for each patient, and the 12 most representative features were selected by using the agglomerative hierarchical clustering method. The binary classification task of the two groups was carried out by using four different machine-learning algorithms (i.e., linear support vector machine (SVM), radial basis function (RBF) SVM, logistic regression (LR), and random forest (RF)). Accuracy, sensitivity, sensibility, and the area under the curve (AUC) were calculated for each of them. Results: The best performance was achieved using the RF classifier (AUC = 0.59, 95% confidence interval 0.57–0.60; sensitivity = 0.56, 95% CI 0.54–0.58; specificity = 0.61, 95% CI 0.59–0.63; accuracy = 0.58, 95% CI 0.57–0.59). Conclusions: DBT-based radiomic analysis seems to have only limited potential in discriminating benign from malignant microcalcifications.

Radiomics is emerging as a promising and useful tool in cardiac magnetic resonance (CMR) imaging applications. Accordingly, the purpose of this study was to investigate, for the first time, the effect of image preprocessing and filtering on radiomic features estimation from quantitative CMR T1 and T2 mapping. Specifically, T1 and T2 maps of 26 patients with hypertrophic cardiomyopathy (HCM) were used to estimate 98 radiomic features for 7 different resampling voxel sizes (at fixed bin width), 9 different bin widths (at fixed resampling voxel size), and 7 different spatial filters (at fixed resampling voxel size/bin width). While we found a remarkable dependence of myocardial radiomic features from T1 and T2 mapping on image filters, many radiomic features showed a limited sensitivity to resampling voxel size/bin width, in terms of intraclass correlation coefficient (>0.75) and coefficient of variation (

Various in vivo experimental works carried out on different animals and organs have shown that it is possible to reduce the damage caused to healthy tissue still preserving the therapeutic efficacy on the tumor tissue, by drastically reducing the total time of dose delivery (in vivo experiments. Moreover, the work discusses the saturation problems of the most common radiotherapy dosimeters when used in the very high dose-per-pulse FLASH conditions and provides some preliminary experimental data on their behavior.

Since Favaudon’s paper of 2014, there has been an increasing interest in FLASH radiotherapy. The FLASH modality could represent a breakthrough in radiation oncology; nevertheless, it brings new scientific and technological challenges. Currently, one of the main limits the scientific community has to cope with is the lack of a common technological platform to experiment with. Considering this framework, the possibility of readapting existing linac platforms to produce a FLASH beam is particularly attractive and different attempts have been already made. The purpose of this article is to illustrate how it is possible to transform a dedicated Intra Operative Radio Therapy (IORT) mobile linac into a FLASH research machine. Compared to the modification required by a standard medical linac, such transformation is easier, does not affect the machine settings and can be rapidly performed by the final user. NOVAC 7 is an IORT linac which can reach a maximum dose-per-pulse up to 13 cGy/pulse (average dose rate 39 Gy/min); such dose rate can be significantly increased by modifying the collimation system. Four different Source Surface Distance (SSD) can be obtained: -Clinical reference configuration; -Upper applicator only (SSD 50 cm); -Monitor chambers housing only (SSD 7 cm); -Dismounted monitor chambers (SSD 1.6 cm). The fourth configuration allows reaching values of dose-per-pulse up to around 18 Gy/pulse and dose rates up to around 500 Gy/s, at a Pulse Repetition Frequency (PRF) of 30 Hz. The other three configurations can be obtained without using any tool and without changing NOVAC settings, until reaching a FLASH dose rate in the third configuration. For FLASH configurations, relative and absolute dosimetric characterization of the beam were performed using radiochromic films EBT3. NOVAC7 transformed in FLASH mode can be used both for dosimetric testing and characterization of detectors and for radiobiological studies on cells and organoids, offering a wide range of dose-per-pulse, from 3 cGy/pulse up to 18 Gy/pulse; dose rates correspondingly change from 3 cGy/s up to 540 Gy/s.

Owing to the self-renewing reactive oxygen species scavenger capability of cerium oxide nanoparticles (nanoceria), we tested in vivo radioprotective effects on stem cells and tissue regeneration using low-dose irradiated planarians as model system. We treated planarians with nanoceria or gum Arabic, as control, and we analyzed the expression of stem cell molecular markers and tissue regeneration capability, as well as cell death and DNA damage in non-irradiated and in low-dose irradiated animals. Our findings show that nanoceria increase the number of stem cells and tissue regenerative capability, and reduce cell death and DNA damage after low-dose irradiation, suggesting a protective role on stem cells.

Although the molecular defect causing Becker muscular dystrophy (BMD) has been identified, the biochemical mechanisms that lead to muscle necrosis remain unclear. Exercise-related muscle metabolism in 9 mildly affected BMD patients was assessed by muscle 31-phosphorus magnetic resonance spectroscopy (P-31 MRS) during an incremental workload. Compared with normal controls, BMD patients showed deregulation of resting pH and intramuscular membrane breakdown. We also observed increased reliance upon anaerobic metabolism during sustained submaximal contraction and maintenance of oxidative function during recovery. Muscle Nerve 44: 816-819, 2011

As the use of digital radiographic equipment in the morphological imaging field is becoming largely diffuse, the research of new and more performing devices from public institutions and industrial companies is in constant progress. Many of these devices are based on solid-state detectors as X-ray sensors. Semiconductor pixel detectors, originally developed in the high energy physics environment, have been then proposed as digital detector for medical imaging applications. In this paper a digital single photon counting device, based on silicon and GaAs pixel detectors, is presented. The detector is a thin slab of semiconductor crystal equipped with an array of 64 by 64 square contacts, 170-μm side. The data read-out is performed by a VLSI integrated circuit named Photon Counting Chip (PCC), developed within the MEDIPIX collaboration. Each chip cell geometrically matches the sensor pixel. It contains a charge preamplifier, a threshold comparator and a 15 bits pseudo-random counter and it is coupled to the detector by means of bump-bonding. Most important advantages of such a system, with respect to a traditional X-rays film/screen device, are the wider linear dynamic range (3x10 4 ) and the higher performance in terms of MTF and DQE. Electronics read-out performance as well as imaging capabilities of the digital device will be presented. Images of mammographic phantoms acquired with a standard mammographic tube will be compared with radiographs obtained with traditional film/screen systems.