Performance Analysis of Six Semi-Automated Tumour Delineation Methods on [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in Patients with Head and Neck Cancer.

Background. Head and neck cancer (HNC) is the seventh most common neoplastic disorder at the global level. Contouring HNC lesions on [18F] Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans plays a fundamental role for diagnosis, risk assessment, radiotherapy planning and post-treatment evaluation. However, manual contouring is a lengthy and tedious procedure which requires significant effort from the clinician. Methods. We evaluated the performance of six hand-crafted, training-free methods (four threshold-based, two algorithm-based) for the semi-automated delineation of HNC lesions on FDG PET/CT. This study was carried out on a single-centre population of n=103 subjects, and the standard of reference was manual segmentation generated by nuclear medicine specialists. Figures of merit were the Sørensen-Dice coefficient (DSC) and relative volume difference (RVD). Results. Median DSC ranged between 0.595 and 0.792, median RVD between -22.0% and 87.4%. Click and draw and Nestle's methods achieved the best segmentation accuracy (median DSC, respectively, 0.792 ± 0.178 and 0.762 ± 0.107; median RVD, respectively, -21.6% ± 1270.8% and -32.7% ± 40.0%) and outperformed the other methods by a significant margin. Nestle's method also resulted in a lower dispersion of the data, hence showing stronger inter-patient stability. The accuracy of the two best methods was in agreement with the most recent state-of-the art results. Conclusions. Semi-automated PET delineation methods show potential to assist clinicians in the segmentation of HNC lesions on FDG PET/CT images, although manual refinement may sometimes be needed to obtain clinically acceptable ROIs.

PET Radiomics and Response to Immunotherapy in Lung Cancer: A Systematic Review of the Literature.

The aim of this review is to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patient candidates or those undergoing immunotherapy. MATERIALS AND METHODS: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were independently reviewed to evaluate study inclusion. Duplicate, out-of-topic, and review papers, or editorials, articles, and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302. RESULTS: Fifteen papers were included, thirteen were qualified as using conventional radiomics approaches, and two used deep learning radiomics. The content of each study was different; indeed, seven papers investigated the potential ability of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreover, two evaluated the prediction of response, and four investigated the utility of radiomics to predict the response to immunotherapy. Finally, two papers investigated the prediction of adverse events due to immunotherapy. CONCLUSIONS: Radiomics is promising for the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overcome.

Size measurement of lung nodules on CT: which diameter is most stable to inter-observer variability?

Indeterminate lung nodules detected on CT are common findings in the clinical practice, and the correct assessment of their size is critical for patient evaluation and management. We compared the stability of three definitions of nodule diameter (Feret's mean diameter, Martin's mean diameter and area-equivalent diameter) to inter-observer variability on a population of 336 solid nodules from 207 subjects. We found that inter-observer agreement was highest with Martin's mean diameter (intra-class correlation coefficient = 0.977, 95% Confidence interval = 0.977-0.978), followed by area-equivalent diameter (0.972, 0.971-0.973) and Feret's mean diameter (0.965, 0.964-0.966). The differences were statistically significant. In conclusion, although all the three diameter definitions achieved very good inter-observer agreement (ICC > 0.96), Martin's mean diameter was significantly better than the others. Future guidelines may consider adopting Martin's mean diameter as an alternative to the currently used Feret's (caliper) diameter for assessing the size of lung nodules on CT.

Radiomics and theranostics with molecular and metabolic probes in prostate cancer: toward a personalized approach.

INTRODUCTION: In the last decade, two new radionuclide-based therapies, 223Radichloride and radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA), have been approved by the regulatory authorities for the management of castrate-resistant prostate cancer (PCa). AREAS COVERED: The basic principles of PCa molecular imaging are illustrated, with a particular attention to the combined use of diagnosis and therapy in a unique approach (the so-called theranostics) for response prediction and assessment in patients submitted to 223Radichloride or PSMA targeted therapies. In this perspective, the potential of radiomics, an emerging discipline based on the extraction of quantitative features from medical images, is covered. EXPERT OPINION: Theranostic metabolic and molecular probes have been successfully applied to predict and monitor response to radionuclide-based therapies. In particular, both 99mTc-MDP and 18F-NaF resulted useful tools for personalized dosimetry and prognostic stratification before 223Ra-therapy, while PSMA-ligands, alone or in combination with 18F-FDG, provided valuable information to select patients who are more likely to benefit from RLT and getting information on PCa grade of differentiation and aggressiveness. In spite of its high potential, PET-radiomics for PCa is still at an embryonic phase and needs further validation.

Form Factors as Potential Imaging Biomarkers to Differentiate Benign vs. Malignant Lung Lesions on CT Scans.

Indeterminate lung nodules detected on CT scans are common findings in clinical practice. Their correct assessment is critical, as early diagnosis of malignancy is crucial to maximise the treatment outcome. In this work, we evaluated the role of form factors as imaging biomarkers to differentiate benign vs. malignant lung lesions on CT scans. We tested a total of three conventional imaging features, six form factors, and two shape features for significant differences between benign and malignant lung lesions on CT scans. The study population consisted of 192 lung nodules from two independent datasets, containing 109 (38 benign, 71 malignant) and 83 (42 benign, 41 malignant) lung lesions, respectively. The standard of reference was either histological evaluation or stability on radiological followup. The statistical significance was determined via the Mann-Whitney U nonparametric test, and the ability of the form factors to discriminate a benign vs. a malignant lesion was assessed through multivariate prediction models based on Support Vector Machines. The univariate analysis returned four form factors (Angelidakis compactness and flatness, Kong flatness, and maximum projection sphericity) that were significantly different between the benign and malignant group in both datasets. In particular, we found that the benign lesions were on average flatter than the malignant ones; conversely, the malignant ones were on average more compact (isotropic) than the benign ones. The multivariate prediction models showed that adding form factors to conventional imaging features improved the prediction accuracy by up to 14.5 pp. We conclude that form factors evaluated on lung nodules on CT scans can improve the differential diagnosis between benign and malignant lesions.

The Role and Potential of 18F-FDG PET/CT in Malignant Melanoma: Prognostication, Monitoring Response to Targeted and Immunotherapy, and Radiomics.

Novel therapeutic approaches, consisting of immune check-point inhibitors (ICIs) and molecularly targeted therapy, have thoroughly changed the clinical management of malignant melanoma (MM), the most frequent and deadly skin cancer. Since only 30-40% of MM patients respond to ICIs, imaging biomarkers suitable for the pre-therapeutic stratification and response assessment are warmly welcome. In this scenario, positron emission computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has been successfully utilized for advanced MM staging and therapy response evaluation. Furthermore, several PET-derived parameters (SUVmax, MTV, TLG) were particularly impactful for the prognostic evaluation of patients submitted to targeted and immunotherapy. In this review, we performed a web-based and desktop research on the clinical applications of 18F-FDG PET/CT in MM, with a particular emphasis on the various metabolic criteria developed for interpreting PET/CT scan in patients undergoing immunotherapy or targeted therapy or a combination of both. Furthermore, the emerging role of radiomics, a quantitative approach to medical imaging applying analysis methodology derived by the field of artificial intelligence, was examined in the peculiar context, putting a particular emphasis on the potential of this discipline to support clinicians in the delicate process of building patient-tailored pathways of care.

Impact of Lesion Delineation and Intensity Quantisation on the Stability of Texture Features from Lung Nodules on CT: A Reproducible Study.

Computer-assisted analysis of three-dimensional imaging data (radiomics) has received a lot of research attention as a possible means to improve the management of patients with lung cancer. Building robust predictive models for clinical decision making requires the imaging features to be stable enough to changes in the acquisition and extraction settings. Experimenting on 517 lung lesions from a cohort of 207 patients, we assessed the stability of 88 texture features from the following classes: first-order (13 features), Grey-level Co-Occurrence Matrix (24), Grey-level Difference Matrix (14), Grey-level Run-length Matrix (16), Grey-level Size Zone Matrix (16) and Neighbouring Grey-tone Difference Matrix (five). The analysis was based on a public dataset of lung nodules and open-access routines for feature extraction, which makes the study fully reproducible. Our results identified 30 features that had good or excellent stability relative to lesion delineation, 28 to intensity quantisation and 18 to both. We conclude that selecting the right set of imaging features is critical for building clinical predictive models, particularly when changes in lesion delineation and/or intensity quantisation are involved.

Comparative evaluation of conventional and deep learning methods for semi-automated segmentation of pulmonary nodules on CT.

BACKGROUND: Accurate segmentation of pulmonary nodules on computed tomography (CT) scans plays a crucial role in the evaluation and management of patients with suspicion of lung cancer (LC). When performed manually, not only the process requires highly skilled operators, but is also tiresome and time-consuming. To assist the physician in this task several automated and semi-automated methods have been proposed in the literature. In recent years, in particular, the appearance of deep learning has brought about major advances in the field. METHODS: Twenty-four (12 conventional and 12 based on deep learning) semi-automated-'one-click'-methods for segmenting pulmonary nodules on CT were evaluated in this study. The experiments were carried out on two datasets: a proprietary one (383 images from a cohort of 111 patients) and a public one (259 images from a cohort of 100). All the patients had a positive transcript for suspect pulmonary nodules. RESULTS: The methods based on deep learning clearly outperformed the conventional ones. The best performance [Sørensen-Dice coefficient (DSC)] in the two datasets was, respectively, 0.853 and 0.763 for the deep learning methods, and 0.761 and 0.704 for the traditional ones. CONCLUSIONS: Deep learning is a viable approach for semi-automated segmentation of pulmonary nodules on CT scans.

Experimental Assessment of Color Deconvolution and Color Normalization for Automated Classification of Histology Images Stained with Hematoxylin and Eosin.

Histological evaluation plays a major role in cancer diagnosis and treatment. The appearance of H&E-stained images can vary significantly as a consequence of differences in several factors, such as reagents, staining conditions, preparation procedure and image acquisition system. Such potential sources of noise can all have negative effects on computer-assisted classification. To minimize such artefacts and their potentially negative effects several color pre-processing methods have been proposed in the literature-for instance, color augmentation, color constancy, color deconvolution and color transfer. Still, little work has been done to investigate the efficacy of these methods on a quantitative basis. In this paper, we evaluated the effects of color constancy, deconvolution and transfer on automated classification of H&E-stained images representing different types of cancers-specifically breast, prostate, colorectal cancer and malignant lymphoma. Our results indicate that in most cases color pre-processing does not improve the classification accuracy, especially when coupled with color-based image descriptors. Some pre-processing methods, however, can be beneficial when used with some texture-based methods like Gabor filters and Local Binary Patterns.

Value of Shape and Texture Features from 18F-FDG PET/CT to Discriminate between Benign and Malignant Solitary Pulmonary Nodules: An Experimental Evaluation.

In this paper, we investigate the role of shape and texture features from 18F-FDG PET/CT to discriminate between benign and malignant solitary pulmonary nodules. To this end, we retrospectively evaluated cross-sectional data from 111 patients (64 males, 47 females, age = 67.5 ± 11.0) all with histologically confirmed benign (n=39) or malignant (n=72) solitary pulmonary nodules. Eighteen three-dimensional imaging features, including conventional, texture, and shape features from PET and CT were tested for significant differences (Wilcoxon-Mann-Withney) between the benign and malignant groups. Prediction models based on different feature sets and three classification strategies (Classification Tree, k-Nearest Neighbours, and Naïve Bayes) were also evaluated to assess the potential benefit of shape and texture features compared with conventional imaging features alone. Eight features from CT and 15 from PET were significantly different between the benign and malignant groups. Adding shape and texture features increased the performance of both the CT-based and PET-based prediction models with overall accuracy gain being 3.4-11.2 pp and 2.2-10.2 pp, respectively. In conclusion, we found that shape and texture features from 18F-FDG PET/CT can lead to a better discrimination between benign and malignant lung nodules by increasing the accuracy of the prediction models by an appreciable margin.

Classification Model to Estimate MIB-1 (Ki 67) Proliferation Index in NSCLC Patients Evaluated With 18F-FDG-PET/CT.

BACKGROUND/AIM: Proliferation biomarkers such as MIB-1 are strong predictors of clinical outcome and response to therapy in patients with non-small-cell lung cancer, but they require histological examination. In this work, we present a classification model to predict MIB-1 expression based on clinical parameters from positron emission tomography. PATIENTS AND METHODS: We retrospectively evaluated 78 patients with histology-proven non-small-cell lung cancer (NSCLC) who underwent 18F-FDG-PET/CT for clinical examination. We stratified the population into a low and high proliferation group using MIB-1=25% as cut-off value. We built a predictive model based on binary classification trees to estimate the group label from the maximum standardized uptake value (SUVmax) and lesion diameter. RESULTS: The proposed model showed ability to predict the correct proliferation group with overall accuracy >82% (78% and 86% for the low- and high-proliferation group, respectively). CONCLUSION: Our results indicate that radiotracer activity evaluated via SUVmax and lesion diameter are correlated with tumour proliferation index MIB-1.

Texture Analysis on [18F]FDG PET/CT in Non-Small-Cell Lung Cancer: Correlations Between PET Features, CT Features, and Histological Types.

PURPOSE: The study aims to investigate the correlations between positron emission tomography (PET) texture features, X-ray computed tomography (CT) texture features, and histological subtypes in non-small-cell lung cancer evaluated with 2-deoxy-2-[18F]fluoro-D-glucose PET/CT. PROCEDURES: We retrospectively evaluated the baseline PET/CT scans of 81 patients with histologically proven non-small-cell lung cancer. Feature extraction and statistical analysis were carried out on the Matlab platform (MathWorks, Natick, USA). RESULTS: Intra-CT correlation analysis revealed a strong positive correlation between volume of the lesion (CTvol) and maximum density (CTmax), and between kurtosis (CTkrt) and maximum density (CTmax). A moderate positive correlation was found between volume (CTvol) and average density (CTmean), and between kurtosis (CTkrt) and average density (CTmean). Intra-PET analysis identified a strong positive correlation between the radiotracer uptake (SUVmax, SUVmean) and its degree of variability/disorder throughout the lesion (SUVstd, SUVent). Conversely, there was a strong negative correlation between the uptake (SUVmax, SUVmean) and its degree of uniformity (SUVuni). There was a positive moderate correlation between the metabolic tumor volume (MTV) and radiotracer uptake (SUVmax, SUVmean). Inter (PET-CT) correlation analysis identified a very strong positive correlation between the volume of the lesion at CT (CTvol) and the metabolic volume (MTV), a moderate positive correlation between average tissue density (CTmean) and radiotracer uptake (SUVmax, SUVmean), and between kurtosis at CT (CTkrt) and metabolic tumor volume (MTV). Squamous cell carcinomas had larger volume higher uptake, stronger PET variability and lower uniformity than the other subtypes. By contrast, adenocarcinomas exhibited significantly lower uptake, lower variability and higher uniformity than the other subtypes. CONCLUSIONS: Significant associations emerged between PET features, CT features, and histological type in NSCLC. Texture analysis on PET/CT shows potential to differentiate between histological types in patients with non-small-cell lung cancer.

Evaluation of Shape and Textural Features from CT as Prognostic Biomarkers in Non-small Cell Lung Cancer.

BACKGROUND/AIM: We retrospectively investigated the prognostic potential (correlation with overall survival) of 9 shape and 21 textural features from non-contrast-enhanced computed tomography (CT) in patients with non-small-cell lung cancer. MATERIALS AND METHODS: We considered a public dataset of 203 individuals with inoperable, histologically- or cytologically-confirmed NSCLC. Three-dimensional shape and textural features from CT were computed using proprietary code and their prognostic potential evaluated through four different statistical protocols. RESULTS: Volume and grey-level run length matrix (GLRLM) run length non-uniformity were the only two features to pass all four protocols. Both features correlated negatively with overall survival. The results also showed a strong dependence on the evaluation protocol used. CONCLUSION: Tumour volume and GLRLM run-length non-uniformity from CT were the best predictor of survival in patients with non-small-cell lung cancer. We did not find enough evidence to claim a relationship with survival for the other features.

Multi-class texture analysis in colorectal cancer histology.

Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies.