The Primacy of High b-Value 3T-DWI Radiomics in the Prediction of Clinically Significant Prostate Cancer

Predicting clinically significant prostate cancer (csPCa) is crucial in PCa management. 3T-magnetic resonance (MR) systems may have a novel role in quantitative imaging and early csPCa prediction, accordingly. In this study, we develop a radiomic model for predicting csPCa based solely on native b2000 diffusion weighted imaging (DWIb2000) and debate the effectiveness of apparent diffusion coefficient (ADC) in the same task. In total, 105 patients were retrospectively enrolled between January–November 2020, with confirmed csPCa or ncsPCa based on biopsy. DWIb2000 and ADC images acquired with a 3T-MRI were analyzed by computing 84 local first-order radiomic features (RFs). Two predictive models were built based on DWIb2000 and ADC, separately. Relevant RFs were selected through LASSO, a support vector machine (SVM) classifier was trained using repeated 3-fold cross validation (CV) and validated on a holdout set. The SVM models rely on a single couple of uncorrelated RFs (ρ < 0.15) selected through Wilcoxon rank-sum test (p ≤ 0.05) with Holm–Bonferroni correction. On the holdout set, while the ADC model yielded AUC = 0.76 (95% CI, 0.63–0.96), the DWIb2000 model reached AUC = 0.84 (95% CI, 0.63–0.90), with specificity = 75%, sensitivity = 90%, and informedness = 0.65. This study establishes the primary role of 3T-DWIb2000 in PCa quantitative analyses, whilst ADC can remain the leading sequence for detection

Reproducibility of CT-based radiomic features against image resampling and perturbations for tumour and healthy kidney in renal cancer patients.

Computed Tomography (CT) is widely used in oncology for morphological evaluation and diagnosis, commonly through visual assessments, often exploiting semi-automatic tools as well. Well-established automatic methods for quantitative imaging offer the opportunity to enrich the radiologist interpretation with a large number of radiomic features, which need to be highly reproducible to be used reliably in clinical practice. This study investigates feature reproducibility against noise, varying resolutions and segmentations (achieved by perturbing the regions of interest), in a CT dataset with heterogeneous voxel size of 98 renal cell carcinomas (RCCs) and 93 contralateral normal kidneys (CK). In particular, first order (FO) and second order texture features based on both 2D and 3D grey level co-occurrence matrices (GLCMs) were considered. Moreover, this study carries out a comparative analysis of three of the most commonly used interpolation methods, which need to be selected before any resampling procedure. Results showed that the Lanczos interpolation is the most effective at preserving original information in resampling, where the median slice resolution coupled with the native slice spacing allows the best reproducibility, with 94.6% and 87.7% of features, in RCC and CK, respectively. GLCMs show their maximum reproducibility when used at short distances

Automatically extracted machine learning features from preoperative CT to early predict microvascular invasion in HCC: the role of the Zone of Transition (ZOT)

open12noMicrovascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI−) became 169 (62 MVI+ and 107 MVI−) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI−), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70–0.93), p∼10^−5), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status.noneMatteo Renzulli, Margherita Mottola, Francesca Coppola, Maria Adriana Cocozza, Silvia Malavasi, Arrigo Cattabriga, Giulio Vara, Matteo Ravaioli, Matteo Cescon, Francesco Vasuri, Rita Golfieri, Alessandro BevilacquaMatteo Renzulli, Margherita Mottola, Francesca Coppola, Maria Adriana Cocozza, Silvia Malavasi, Arrigo Cattabriga, Giulio Vara, Matteo Ravaioli, Matteo Cescon, Francesco Vasuri, Rita Golfieri, Alessandro Bevilacqu

Radiomic Features from Post-Operative 18F-FDG PET/CT and CT Imaging Associated with Locally Recurrent Rectal Cancer: Preliminary Findings

Locally Recurrent Rectal Cancer (LRRC) remains a major clinical concern, it rapidly invades pelvic organs and nerve roots, causing severe symptoms. Curative-intent salvage therapy offers the only potential for cure but it has a higher chance of success when LRRC is diagnosed at an early stage. Imaging diagnosis of LRRC is very challenging due to fibrosis and inflammatory pelvic tissue which can mislead even the most expert reader. This study exploited a radiomic analysis to enrich, through quantitative features, the characterization of tissue properties, thus favouring an accurate detection of LRRC by Computed Tomography (CT) and 18F-FDG-Positron Emission Tomography/CT (PET/CT). Of 563 eligible patients, undergoing radical resection (R0) of primary RC, 57 patients with suspected LRRC were included, 33 of which histologically confirmed. After manually segmenting suspected LRRC in CT and PET/CT, 144 radiomic features (RFs) were generated, and RFs were investigated for univariate significant discriminations (Wilcoxon rank-sum test, p<0.050) of LRRC from NO LRRC. Five RFs in PET/CT (p<0.017) and 2 in CT (p<0.022) enabled, individually, a clear distinction of the groups, and one RF was shared by PET/CT and CT. Besides confirming the potential role of radiomics to advance LRRC diagnosis, the aforementioned shared RF describes LRRC as tissues having high local inhomogeneity due to evolving tissue’s properties

The Heterogeneity of Skewness in T2W-Based Radiomics Predicts the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Our study aimed to investigate whether radiomics on MRI sequences can differentiate responder (R) and non-responder (NR) patients based on the tumour regression grade (TRG) assigned after surgical resection in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Eighty-five patients undergoing primary staging with MRI were retrospectively evaluated, and 40 patients were finally selected. The ROIs were manually outlined in the tumour site on T2w sequences in the oblique-axial plane. Based on the TRG, patients were grouped as having either a complete or a partial response (TRG = (0,1), n = 15). NR patients had a minimal or poor nCRT response (TRG = (2,3), n = 25). Eighty-four local first-order radiomic features (RFs) were extracted from tumour ROIs. Only single RFs were investigated. Each feature was selected using univariate analysis guided by a one-tailed Wilcoxon rank-sum. ROC curve analysis was performed, using AUC computation and the Youden index (YI) for sensitivity and specificity. The RF measuring the heterogeneity of local skewness of T2w values from tumour ROIs differentiated Rs and NRs with a p-value ≈ 10−5; AUC = 0.90 (95%CI, 0.73–0.96); and YI = 0.68, corresponding to 80% sensitivity and 88% specificity. In conclusion, higher heterogeneity in skewness maps of the baseline tumour correlated with a greater benefit from nCR

Sviluppo e ottimizzazione di algoritmi per predire la risposta alla terapia di resincronizzazione cardiaca

La necessità di indagine sul fronte dell’insufficienza cardiaca deriva dall’elevato impatto sociale della patologia, non soltanto per l’effetto invalidante sulla condizione del paziente che ne è affetto, bensì anche per la notevole incidenza sui servizi sanitari nazionali, per l’importante valore di mortalità e morbilità che ne è associato. Il numero di ospedalizzazioni per scompenso cardiaco è consistente; ciò rende ragione dell’elevato assorbimento di risorse dovuto a questa patologia. Il razionale dell’impiego della Terapia di Resincronizzazione Cardiaca (CRT) consiste nella correzione della dissincronia cardiaca come causa di disfunzione meccanica atriale e ventricolare. Il metodo analitico sviluppato origina dalle indagini sugli spostamenti dell’elettrocatetere posizionato in Seno Coronarico, sulla base del fatto che il sito di stimolazione risulta un fattore determinante per la buona risposta alla terapia. Dovendo studiare le posizioni nel tempo del catetere, si è pensato di valutarne le variazioni nel periodo pre e post attivazione della CRT ricostruendone la traiettoria in 3D. Lo studio parametrico di quest’ultima ha permesso di individuare un indice predittore della risposta alla CRT al follow-up a sei mesi. La prosecuzione della ricerca presentata ha l’intento di migliorare gli algoritmi di elaborazione dei dati per rendere più robuste le misure, sfruttando tecniche che possano aumentare riproducibilità, ripetibilità, e ininfluenza rispetto alla variabilità delle condizioni analitiche. Sviluppando nuovi modelli si è eliminata l'interazione dell'operatore nelle fasi d'indagine, rendendo le analisi completamente automatiche. I metodi sono stati testati e applicati

Calcolo dei parametri perfusionali epatici mediante TC dinamica secondo un modello dual-input mono-compartimentale

INTRODUZIONE. In oncologia, lo studio perfusionale consente di individuare i processi angiogenici tipici dei tumori e di monitorare gli effetti delle terapie anti-angiogeniche sulle sedi target. Una delle tecniche di imaging funzionale è la Tomografia Computerizzata perfusionale (TCp) eseguita con mezzo di contrasto (MdC), che consente di ricostruire le Time Concentration Curve (TCC) del MdC nei vasi sanguigni e nel tessuto. La convoluzione tra la TCC vascolare e la Impulse Residue Function (IRF) restituisce la TCC tessutale. Valutare la perfusione significa calcolare l’apporto di sangue al tessuto, mediante l’analisi della cinetica del MdC. Tra i metodi preposti vi sono il Maximum Slope (MS) e la deconvoluzione, che vuole stimare la IRF dalle TCC estratte, risolvendo quindi il problema inverso. OBIETTIVI. Il lavoro di Tesi nasce per calcolare i parametri perfusionali epatici, con modello mono compartimentale dual input. A questo scopo, si volevano approfondire le relazioni esistenti tra i diversi elementi coinvolti nel processo diretto di convoluzione, con particolare interesse per la IRF. METODI. È stato individuato un set di curve idonee a rappresentare la IRF e ne sono stati definiti metodi di calcolo automatici dei parametri, traendo informazioni dalle TCC reali. È stato quindi sviluppato un simulatore per generare TCC di tessuto, attraverso la convoluzione della IRF con TCC vascolari. Si è studiato un metodo di calcolo dei parametri perfusionali, effettuati sugli output del simulatore. I dati perfusionali sono stati analizzati con un classificatore non supervisionato, per individuare gruppi significativi di pazienti. RISULTATI. Il metodo è stato applicato per lo studio perfusionale di 10 pazienti. I dati ottenuti sono stati confrontati con quelli calcolati indipendentemente con MS sulle stesse curve, ottenuta correlazione e proporzionalità tra le misure. Inoltre, sono stati rilevati gruppi di esami con caratteristiche cliniche simili

New methodologies in CT perfusion and MRI analysis to develop cancer imaging biomarkers

Quantitative imaging in oncology aims at developing imaging biomarkers for diagnosis and prediction of cancer aggressiveness and therapy response before any morphological change become visible. This Thesis exploits Computed Tomography perfusion (CTp) and multiparametric Magnetic Resonance Imaging (mpMRI) for investigating diverse cancer features on different organs. I developed a voxel-based image analysis methodology in CTp and extended its use to mpMRI, for performing precise and accurate analyses at single-voxel level. This is expected to improve reproducibility of measurements and cancer mechanisms’ comprehension and clinical interpretability. CTp has not entered the clinical routine yet, although its usefulness in the monitoring of cancer angiogenesis, due to different perfusion computing methods yielding unreproducible results. Instead, machine learning applications in mpMRI, useful to detect imaging features representative of cancer heterogeneity, are mostly limited to clinical research, because of results’ variability and difficult interpretability, which make clinicians not confident in clinical applications. In hepatic CTp, I investigated whether, and under what conditions, two widely adopted perfusion methods, Maximum Slope (MS) and Deconvolution (DV), could yield reproducible parameters. To this end, I developed signal processing methods to model the first pass kinetics and remove any numerical cause hampering the reproducibility. In mpMRI, I proposed a new approach to extract local first-order features, aiming at preserving spatial reference and making their interpretation easier. In CTp, I found out the cause of MS and DV non-reproducibility: MS and DV represent two different states of the system. Transport delays invalidate MS assumptions and, by correcting MS formulation, I have obtained the voxel-based equivalence of the two methods. In mpMRI, the developed predictive models allowed (i) detecting rectal cancers responding to neoadjuvant chemoradiation showing, at pre-therapy, sparse coarse subregions with altered density, and (ii) predicting clinically significant prostate cancers stemming from the disproportion between high- and low- diffusivity gland components

Colormaps of CT perfusion parameters computed using different methods visually match

The Computed Tomography perfusion (CTp) is a promising tool in oncology to characterize hemodynamics of tissues, based on fast and repeated CT scans of the region of interest after contrast agent administration. However, it has difficulty in entering the clinical routine (substantially, except for brain and heart) because of the difficulty of achieving same perfusion maps as equipment or perfusion software change. In this work, we present a proper computing chain for CTp parameters, relying on a robust and accurate voxel-based computation, that permits two widely used techniques, Maximum Slope (MS) and Deconvolution (DV) to reproduce, for the first time, the same perfusion maps. The experiments carried out on 25 examinations of oncologic patients proved an excellent correlation between MS and DV maps, with the worst R^2 = 0:971. This outcome represents a marked step forward in the standardization of CTp studies and encourages further multi-centre analyses

Reproducibility of Computed Tomography perfusion parameters in hepatic multicentre study in patients with colorectal cancer

Objective: The Computed Tomography perfusion (CTp) is a promising tool in oncology to characterize tissue hemodynamics, but the difficulty to achieve reproducible perfusion parameters in several organs, with different methods, contributes to hamper the clinical translation of CTp. The goal of this study is to set up a new approach aiming at achieving multicentre reproducibility of blood flow (BF) values in liver. Methods: 75 patients from two Centres (A and B) underwent an axial liver CTp, including arterial and portal phases. A dedicated workflow addressing modelling and computational aspects was implemented, including a novel two-stage strategy to separate the dual-input contributions of hepatic signals, thus allowing to compute independently both Maximum Slope (MS) and Deconvolution (DV) on the same contributing signals. Results: 95% of patients in A and B showed an excellent voxel-based Pearson correlation ( 65 0.96) between MS and DV BF values, with very low coefficients of variation ( = 0.11 in the worst case). The good concordance is confirmed for the whole cohorts, in single Centres and both, where 2=0.97, 65 0.97, 65 0.96, 65 0.78 and =0.25 are the worst values. Compared with eighteen recent articles, these represent by far the best outcomes. Conclusion: The excellent patient- and cohort-based reproducibility of BF values achieved independently by MS and BV confirms the effectiveness of the approach presented. Significance: Our approach can be used to improve the reproducibility in other CTp multicentre studies, in liver as well as in other organs, with even different clinical questions, and represents a marked step forward towards CTp standardization, favouring the investigation of imaging biomarkers