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Radiomica
Emanuele Neri
Department of Translational Research
University of Pisa
Italian Society of Medical and Interventional Radiology (SIRM)
SIRM Foundation
H2020 EU PROJECT | Topic SC1-DTH-07-2018 | GA: 826494
PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers
Biomarker (definition)
Ideally must be a measurement!
A characteristic that is objectively measured and
evaluated as an indicator of normal biologic processes,
pathogenic processes (abnormal biologic processes), or
biological responses to a therapeutic intervention
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and
conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89-95.
Imaging biomarker vs Pathologic mechanism
2018
Quantitative vs qualitative imaging biomarkers
Qualitative or categorical imaging biomarker
A biomarker that cannot be expressed as a quantity value. All ordinal biomarkers are examples.
Pathological grading systems BI-RADS LI-RADS PI-RADS C-RADS Clinical TNM Stage
A biomarker whose magnitude is expressed as a quantity value.
Volume, diameter, density, intensity, perfusion, diffusion, radiomics features, dose parameters, etc
Quantitative imaging biomarker
NATURE REVIEWS | CLINICAL ONCOLOGY
VOLUME 14 | MARCH 2017 | 175
H2020 EU PROJECT | Topic SC1-DTH-07-2018 | GA: 826494
Typical industrial product development (mean 12 years!!!)
Development of imaging biomarkers:
Translational gaps
“Radiomics” refers to the extraction
and analysis of large amounts of
advanced quantitative imaging
features with high throughput from
medical images.
Radiomics: a new biomarker
Flowchart showing the process of radiomics.
Bin Zhang et al. Clin Cancer Res 2017;23:4259-4269
©2017 by American Association for Cancer Research
PR; 40%
SD; 40%
PD; 20%
RECIST CRITERIA
Materials and methods: feasibility study In progress analysis of more 45 cases:
Exosome mRNA
#6 #3
Population Disease Treatment
NSCLC III-IV STAGE
Pembrolizumab Nivolumab
Liquid Biopsy
CTCs circulating tumour-derived nucleic acids
INF-ƴ PD-L1 TNF-α
E. Neri, M. Del Re, Danesi R. University of Pisa
QUIBIM report for tumour texture
analysis.
Every CT slices has a similar report
Materials and methods
Acquisition of CT images and ROI segmentation with Quibim software
Texture analysis and features extraction
1
2
E. Neri, M. Del Re, Danesi R. University of Pisa
Results: RECIST vs Radiomics
T test results: 4 of 27 Features are significant (p<0,05)
Features Clinical event N Mean St Dev p-value
Cluster Prominence Value PR 4 943.974,5 59.723,8
0,012 SD+PD 6 578.074,5 240.339,3
Cluster Shade Value PR 4 -12.204,8 1.354,3
0,034 SD+PD 6 -7.738,8 3.250,6
Information Measure Of Correlation2 Value PR 4 0,9 0,0
0,077 SD+PD 6 0,8 0,1
Volume Value PR 4 1,5 0,7
0,068 SD+PD 6 3,7 2,3
E. Neri, M. Del Re, Danesi R. University of Pisa
Pearson's Correlation Analysis: Features vs Liquid Biopsy
Parameters
Features Statistics PD-L1 INF-ƴ TNF-α
Information Measure Of Correlation1 Value
Pearson's correlation coefficient
-0,159 -0,593 -0,631
p-value (two-tailed) 0,661 0,071 0,05
Information Measure Of Correlation2 Value
Pearson's correlation coefficient
-0,212 0,479 0,659
p-value (two-tailed) 0,557 0,161 0,038
D2D Value
Pearson's correlation coefficient
0,193 -0,933 -0,639
p-value (two-tailed) 0,594 <0,0001 0,047
Volume Max
Pearson's correlation coefficient
-0,492 0,607
p-value (two-tailed) 0,148 0,063 0,442
Results: Radiomics vs Liquid biopsy
Inverse proportionality
Direct proportionality
Inverse proportionality
Direct proportionality 0,275
• Programmed death-ligand 1 (PD-L1)
• Interferon gamma (IFNγ)
• Tumor necrosis factor alpha (TNFα)
E. Neri, M. Del Re, Danesi R. University of Pisa
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Year of publication
#of articles
2012 2013 2014 2015 2016 2017 2018
Radiomics
Liquid biopsy
Radiomics vs Liquid biopsy in literature
Radiomics: workflow in oncology
Precision Medicine
Personalized Medicine
Radiomic
Biomedical Images
Artificial Intelligence
Quantitative features
extraction Multi-omics data processing
Biobanks
• Risk prediction • Treatment Response
Assessment • Treatment Simulation • Prognosis
Fields of Applications of Radiomics
• Oncologic Imaging (90%)
• Neurodegenerative disease
• Other (polycystic kidney disease, etc)
• Imaging Modalities • Ultrasound
• Computed Tomography • Magnetic Resonance • PET/CT
• PET/MR • X-ray Mammography and Thomosynthesis
• Potentialities • Prediction of response to treatment • Risk assessment • Aggressiveness vs tumor biology
• 120 patients with pathologically-confirmed Head and Neck squamous cell carcinoma of which 101 HPV/P16 positive
• HPV with P16 expression is associated with an increased overall survival
• median follow-up time was of 49.3 months • Oncoradiomics research software using Matlab R2012b
• 544 radiomics features • Grouped into (I) tumor intensity, (II) shape, (III) texture and (IV)
wavelet feature
• The radiomics signature showed prognosis capacity for predicting 5-year survival in the whole population with an AUC of 0.67 (95% CI, 0.58–0.76)
chemoradiotherapy (CRT) bioradiotherapy (BRT)
Radiomic signature as predictive biomarker
Adenocarcinoma, lymphoma, and GIST • Retrospective study • Arterial and venous phases were
evaluated
• Arterial phase • of 47 patients with adenocarcinoma
(AC), 15 GIST and 5 lymphoma
• Venous phase • 48 patients with adenocarcinoma
(AC), 17 GIST and 8 lymphoma
• MaZda 4.6 texture analysis software • developed within the COST
(European Cooperation In The Field Of Scientific And Technical Research) projects B11 and B21
Misclassification rates: lower in the arterial phase Best differential diagnosis • GIST vs lymphoma • Gastric cancer vs lymphoma
Texture analysis as diagnostic biomarker
Haralick’s texture analysis is a statistical technique, known as spatial gray-level dependence matrix method: second-order statistics of pixels at different spacings and direction of adjacent or nearest-neighbor pixels
5 features were able to differentiate between complete responder and non-responder patients affected by rectal cancer (all p < 0.05):
Texture analysis as predictive biomarker
Biomarkers
Phenotype
Genotype
Radiogenomic
Radiomics workflow
Final report and Decision support
Final report and Decision Support
Genomic report
Pathology report
Radiology report
Diagnostic
report
Liquid biopsy report
Decision Support
Diagnostic
report
Artificial Intelligence
Diagnosis Treatment
Biobanks (Digital twins / Patients models)
Biobanche delle immagini
• Le biobanche di imaging possono essere definite come "banche dati organizzate di immagini mediche associate ai biomarcatori di imaging (radiologia e non solo), condivisi tra più ricercatori e collegati ad alter biobanche".
• Le grandi biobanche possono divenire una raccolta di pazienti digitali (Avatar o Gemelli digitali) utilizzabili dall'intelligenza artificiale per simulazioni di progressione di malattia, stima della prognosi e della risposta ai trattamenti
ESR – BBMRI Memorandum Of Understanding
• Description & Aims: The European Biobanking and BioMolecular resources Research Infrastructure (BBMRI-ERIC) and the European Society of Radiology (ESR) established an official collaboration in November 2015, signing a Memorandum of Understanding, which will facilitate development in the integration of imaging data with biobank databases.
• The main goals of the collaboration are to promote the importance and visibility of biomarkers, to coordinate efforts to establish a European imaging biobank infrastructure, and to ensure its linking to existing biobanks.