Biodistribution Assessment of a Novel 68Ga-Labeled Radiopharmaceutical in a Cancer Overexpressing CCK2R Mouse Model: Conventional and Radiomics Methods for Analysis.

The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

Recent Developments in Nanoparticle Formulations for Resveratrol Encapsulation as an Anticancer Agent.

Resveratrol is a polyphenolic compound that has gained considerable attention in the past decade due to its multifaceted therapeutic potential, including anti-inflammatory and anticancer properties. However, its anticancer efficacy is impeded by low water solubility, dose-limiting toxicity, low bioavailability, and rapid hepatic metabolism. To overcome these hurdles, various nanoparticles such as organic and inorganic nanoparticles, liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, gold nanoparticles, zinc oxide nanoparticles, zeolitic imidazolate frameworks, carbon nanotubes, bioactive glass nanoparticles, and mesoporous nanoparticles were employed to deliver resveratrol, enhancing its water solubility, bioavailability, and efficacy against various types of cancer. Resveratrol-loaded nanoparticle or resveratrol-conjugated nanoparticle administration exhibits excellent anticancer potency compared to free resveratrol. This review highlights the latest developments in nanoparticle-based delivery systems for resveratrol, focusing on the potential to overcome limitations associated with the compound's bioavailability and therapeutic effectiveness.

Artificial Intelligence for Classifying the Relationship between Impacted Third Molar and Mandibular Canal on Panoramic Radiographs.

The purpose of this investigation was to evaluate the diagnostic performance of two convolutional neural networks (CNNs), namely ResNet-152 and VGG-19, in analyzing, on panoramic images, the rapport that exists between the lower third molar (MM3) and the mandibular canal (MC), and to compare this performance with that of an inexperienced observer (a sixth year dental student). Utilizing the k-fold cross-validation technique, 142 MM3 images, cropped from 83 panoramic images, were split into 80% as training and validation data and 20% as test data. They were subsequently labeled by an experienced radiologist as the gold standard. In order to compare the diagnostic capabilities of CNN algorithms and the inexperienced observer, the diagnostic accuracy, sensitivity, specificity, and positive predictive value (PPV) were determined. ResNet-152 achieved a mean sensitivity, specificity, PPV, and accuracy, of 84.09%, 94.11%, 92.11%, and 88.86%, respectively. VGG-19 achieved 71.82%, 93.33%, 92.26%, and 85.28% regarding the aforementioned characteristics. The dental student's diagnostic performance was respectively 69.60%, 53.00%, 64.85%, and 62.53%. This work demonstrated the potential use of deep CNN architecture for the identification and evaluation of the contact between MM3 and MC in panoramic pictures. In addition, CNNs could be a useful tool to assist inexperienced observers in more accurately identifying contact relationships between MM3 and MC on panoramic images.

An Overview of In Vitro Assays of 64Cu-, 68Ga-, 125I-, and 99mTc-Labelled Radiopharmaceuticals Using Radiometric Counters in the Era of Radiotheranostics.

Radionuclides are unstable isotopes that mainly emit alpha (α), beta (ß) or gamma (γ) radiation through radiation decay. Therefore, they are used in the biomedical field to label biomolecules or drugs for diagnostic imaging applications, such as positron emission tomography (PET) and/or single-photon emission computed tomography (SPECT). A growing field of research is the development of new radiopharmaceuticals for use in cancer treatments. Preclinical studies are the gold standard for translational research. Specifically, in vitro radiopharmaceutical studies are based on the use of radiopharmaceuticals directly on cells. To date, radiometric ß- and γ-counters are the only tools able to assess a preclinical in vitro assay with the aim of estimating uptake, retention, and release parameters, including time- and dose-dependent cytotoxicity and kinetic parameters. This review has been designed for researchers, such as biologists and biotechnologists, who would like to approach the radiobiology field and conduct in vitro assays for cellular radioactivity evaluations using radiometric counters. To demonstrate the importance of in vitro radiopharmaceutical assays using radiometric counters with a view to radiogenomics, many studies based on 64Cu-, 68Ga-, 125I-, and 99mTc-labeled radiopharmaceuticals have been revised and summarized in this manuscript.

Anti-Arthritic and Anti-Cancer Activities of Polyphenols: A Review of the Most Recent In Vitro Assays.

Polyphenols have gained widespread attention as they are effective in the prevention and management of various diseases, including cancer diseases (CD) and rheumatoid arthritis (RA). They are natural organic substances present in fruits, vegetables, and spices. Polyphenols interact with various kinds of receptors and membranes. They modulate different signal cascades and interact with the enzymes responsible for CD and RA. These interactions involve cellular machinery, from cell membranes to major nuclear components, and provide information on their beneficial effects on health. These actions provide evidence for their pharmaceutical exploitation in the treatment of CD and RA. In this review, we discuss different pathways, modulated by polyphenols, which are involved in CD and RA. A search of the most recent relevant publications was carried out with the following criteria: publication date, 2012-2022; language, English; study design, in vitro; and the investigation of polyphenols present in extra virgin olive, grapes, and spices in the context of RA and CD, including, when available, the underlying molecular mechanisms. This review is valuable for clarifying the mechanisms of polyphenols targeting the pathways of senescence and leading to the development of CD and RA treatments. Herein, we focus on research reports that emphasize antioxidant properties.

An extended catalogue of ncRNAs in Streptomyces coelicolor reporting abundant tmRNA, RNase-P RNA and RNA fragments derived from pre-ribosomal RNA leader sequences.

Streptomyces coelicolor is a model organism for studying streptomycetes. This genus possesses relevant medical and economical roles, because it produces many biologically active metabolites of pharmaceutical interest, including the majority of commercialized antibiotics. In this bioinformatic study, the transcriptome of S. coelicolor has been analyzed to identify novel RNA species and quantify the expression of both annotated and novel transcripts in solid and liquid growth medium cultures at different times. The major characteristics disclosed in this study are: (i) the diffuse antisense transcription; (ii) the great abundance of transfer-messenger RNAs (tmRNA); (iii) the abundance of rnpB transcripts, paramount for the RNase-P complex; and (iv) the presence of abundant fragments derived from pre-ribosomal RNA leader sequences of unknown biological function. Overall, this study extends the catalogue of ncRNAs in S. coelicolor and suggests an important role of non-coding transcription in the regulation of biologically active molecule production.

A New Preclinical Decision Support System Based on PET Radiomics: A Preliminary Study on the Evaluation of an Innovative 64Cu-Labeled Chelator in Mouse Models.

The 64Cu-labeled chelator was analyzed in vivo by positron emission tomography (PET) imaging to evaluate its biodistribution in a murine model at different acquisition times. For this purpose, nine 6-week-old female Balb/C nude strain mice underwent micro-PET imaging at three different time points after 64Cu-labeled chelator injection. Specifically, the mice were divided into group 1 (acquisition 1 h after [64Cu] chelator administration, n = 3 mice), group 2 (acquisition 4 h after [64Cu]chelator administration, n = 3 mice), and group 3 (acquisition 24 h after [64Cu] chelator administration, n = 3 mice). Successively, all PET studies were segmented by means of registration with a standard template space (3D whole-body Digimouse atlas), and 108 radiomics features were extracted from seven organs (namely, heart, bladder, stomach, liver, spleen, kidney, and lung) to investigate possible changes over time in [64Cu]chelator biodistribution. The one-way analysis of variance and post hoc Tukey Honestly Significant Difference test revealed that, while heart, stomach, spleen, kidney, and lung districts showed a very low percentage of radiomics features with significant variations (p-value < 0.05) among the three groups of mice, a large number of features (greater than 60% and 50%, respectively) that varied significantly between groups were observed in bladder and liver, indicating a different in vivo uptake of the 64Cu-labeled chelator over time. The proposed methodology may improve the method of calculating the [64Cu]chelator biodistribution and open the way towards a decision support system in the field of new radiopharmaceuticals used in preclinical imaging trials.

Deep learning approach for the segmentation of aneurysmal ascending aorta.

Diagnosis of ascending thoracic aortic aneurysm (ATAA) is based on the measurement of the maximum aortic diameter, but size is not a good predictor of the risk of adverse events. There is growing interest in the development of novel image-derived risk strategies to improve patient risk management towards a highly individualized level. In this study, the feasibility and efficacy of deep learning for the automatic segmentation of ATAAs was investigated using UNet, ENet, and ERFNet techniques. Specifically, CT angiography done on 72 patients with ATAAs and different valve morphology (i.e., tricuspid aortic valve, TAV, and bicuspid aortic valve, BAV) were semi-automatically segmented with Mimics software (Materialize NV, Leuven, Belgium), and then used for training of the tested deep learning models. The segmentation performance in terms of accuracy and time inference were compared using several parameters. All deep learning models reported a dice score higher than 88%, suggesting a good agreement between predicted and manual ATAA segmentation. We found that the ENet and UNet are more accurate than ERFNet, with the ENet much faster than UNet. This study demonstrated that deep learning models can rapidly segment and quantify the 3D geometry of ATAAs with high accuracy, thereby facilitating the expansion into clinical workflow of personalized approach to the management of patients with ATAAs.

Deep Learning Whole-Gland and Zonal Prostate Segmentation on a Public MRI Dataset.

BACKGROUND: Prostate volume, as determined by magnetic resonance imaging (MRI), is a useful biomarker both for distinguishing between benign and malignant pathology and can be used either alone or combined with other parameters such as prostate-specific antigen. PURPOSE: This study compared different deep learning methods for whole-gland and zonal prostate segmentation. STUDY TYPE: Retrospective. POPULATION: A total of 204 patients (train/test = 99/105) from the PROSTATEx public dataset. FIELD STRENGTH/SEQUENCE: A 3 T, TSE T2 -weighted. ASSESSMENT: Four operators performed manual segmentation of the whole-gland, central zone + anterior stroma + transition zone (TZ), and peripheral zone (PZ). U-net, efficient neural network (ENet), and efficient residual factorized ConvNet (ERFNet) were trained and tuned on the training data through 5-fold cross-validation to segment the whole gland and TZ separately, while PZ automated masks were obtained by the subtraction of the first two. STATISTICAL TESTS: Networks were evaluated on the test set using various accuracy metrics, including the Dice similarity coefficient (DSC). Model DSC was compared in both the training and test sets using the analysis of variance test (ANOVA) and post hoc tests. Parameter number, disk size, training, and inference times determined network computational complexity and were also used to assess the model performance differences. A P < 0.05 was selected to indicate the statistical significance. RESULTS: The best DSC (P < 0.05) in the test set was achieved by ENet: 91% ± 4% for the whole gland, 87% ± 5% for the TZ, and 71% ± 8% for the PZ. U-net and ERFNet obtained, respectively, 88% ± 6% and 87% ± 6% for the whole gland, 86% ± 7% and 84% ± 7% for the TZ, and 70% ± 8% and 65 ± 8% for the PZ. Training and inference time were lowest for ENet. DATA CONCLUSION: Deep learning networks can accurately segment the prostate using T2 -weighted images. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Performance of Radiomics Features in the Quantification of Idiopathic Pulmonary Fibrosis from HRCT.

BACKGROUND: Our study assesses the diagnostic value of different features extracted from high resolution computed tomography (HRCT) images of patients with idiopathic pulmonary fibrosis. These features are investigated over a range of HRCT lung volume measurements (in Hounsfield Units) for which no prior study has yet been published. In particular, we provide a comparison of their diagnostic value at different Hounsfield Unit (HU) thresholds, including corresponding pulmonary functional tests. METHODS: We consider thirty-two patients retrospectively for whom both HRCT examinations and spirometry tests were available. First, we analyse the HRCT histogram to extract quantitative lung fibrosis features. Next, we evaluate the relationship between pulmonary function and the HRCT features at selected HU thresholds, namely -200 HU, 0 HU, and +200 HU. We model the relationship using a Poisson approximation to identify the measure with the highest log-likelihood. RESULTS: Our Poisson models reveal no difference at the -200 and 0 HU thresholds. However, inferential conclusions change at the +200 HU threshold. Among the HRCT features considered, the percentage of normally attenuated lung at -200 HU shows the most significant diagnostic utility. CONCLUSIONS: The percentage of normally attenuated lung can be used together with qualitative HRCT assessment and pulmonary function tests to enhance the idiopathic pulmonary fibrosis (IPF) diagnostic process.

Lung Segmentation on High-Resolution Computerized Tomography Images Using Deep Learning: A Preliminary Step for Radiomics Studies.

BACKGROUND: The aim of this work is to identify an automatic, accurate, and fast deep learning segmentation approach, applied to the parenchyma, using a very small dataset of high-resolution computed tomography images of patients with idiopathic pulmonary fibrosis. In this way, we aim to enhance the methodology performed by healthcare operators in radiomics studies where operator-independent segmentation methods must be used to correctly identify the target and, consequently, the texture-based prediction model. METHODS: Two deep learning models were investigated: (i) U-Net, already used in many biomedical image segmentation tasks, and (ii) E-Net, used for image segmentation tasks in self-driving cars, where hardware availability is limited and accurate segmentation is critical for user safety. Our small image dataset is composed of 42 studies of patients with idiopathic pulmonary fibrosis, of which only 32 were used for the training phase. We compared the performance of the two models in terms of the similarity of their segmentation outcome with the gold standard and in terms of their resources' requirements. RESULTS: E-Net can be used to obtain accurate (dice similarity coefficient = 95.90%), fast (20.32 s), and clinically acceptable segmentation of the lung region. CONCLUSIONS: We demonstrated that deep learning models can be efficiently applied to rapidly segment and quantify the parenchyma of patients with pulmonary fibrosis, without any radiologist supervision, in order to produce user-independent results.