Nouveaux biomarqueurs d’imagerie phénotypique et Radiomique intégrée pour la médecine de précision

Publications

Année de publication : 2019

Anne-Sophie Dirand, Frédérique Frouin, Irène Buvat (2019 Nov 30)

A downsampling strategy to assess the predictive value of radiomic features.

Scientific reports : 17869 : DOI : 10.1038/s41598-019-54190-2 En savoir plus
Résumé

Many studies are devoted to the design of radiomic models for a prediction task. When no effective model is found, it is often difficult to know whether the radiomic features do not include information relevant to the task or because of insufficient data. We propose a downsampling method to answer that question when considering a classification task into two groups. Using two large patient cohorts, several experimental configurations involving different numbers of patients were created. Univariate or multivariate radiomic models were designed from each configuration. Their performance as reflected by the Youden index (YI) and Area Under the receiver operating characteristic Curve (AUC) was compared to the stable performance obtained with the highest number of patients. A downsampling method is described to predict the YI and AUC achievable with a large number of patients. Using the multivariate models involving machine learning, YI and AUC increased with the number of patients while they decreased for univariate models. The downsampling method better estimated YI and AUC obtained with the largest number of patients than the YI and AUC obtained using the number of available patients and identifies the lack of information relevant to the classification task when no such information exists.

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Claire Provost, Hamid Mammar, Anne Belly-Poinsignon, Olivier Madar, Laurence Champion (2019 Nov 7)

Pharmacokinetic Analysis of [18F]FAZA Dynamic PET Imaging Acquisitions for Highlighting Sacrum Tumor Profiles.

Clinical nuclear medicine : e36-e38 : DOI : 10.1097/RLU.0000000000002813 En savoir plus
Résumé

A patient enrolled in a clinical trial (NCT02802969) with suspicion of chordoma underwent an [F]FAZA PET/CT, a radiolabeled nitroimidazole analog of hypoxia PET imaging. The patient’s images showed a different tumor profile compared to those observed in other hypoxic or nonhypoxic chordoma patients. The motivation for using [F]FAZA pharmacokinetic imaging was to compare this profile with histologically confirmed cases of chordoma. Through visual imaging and quantification of blood and tumor time-activity curves, we excluded the hypothesis that it was a chordoma, diagnosing a paraganglioma.

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Irène Buvat, Fanny Orlhac (2019 Sep 22)

The Dark Side of Radiomics: On the Paramount Importance of Publishing Negative Results.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine : 1543-1544 : DOI : 10.2967/jnumed.119.235325 En savoir plus
Résumé

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Charlotte Laurent, Laure Ricard, Olivier Fain, Irene Buvat, Amir Adedjouma, Michael Soussan, Arsène Mekinian (2019 Aug 29)

PET/MRI in large-vessel vasculitis: clinical value for diagnosis and assessment of disease activity.

Scientific reports : 12388 : DOI : 10.1038/s41598-019-48709-w En savoir plus
Résumé

Diagnosis of large vessel vasculitis (LVV) and evaluation of its inflammatory activity can be challenging. Our aim was to investigate the value of hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) in LVV. All consecutive patients with LVV from the Department of Internal Medicine who underwent PET/MRI were included. Three PET/MRI patterns were defined: (i) « inflammatory, » with positive PET (>liver uptake) and abnormal MRI (stenosis and/or wall thickening); (ii) « fibrous », negative PET (≤liver uptake) and abnormal MRI; and (iii) « normal ». Thirteen patients (10 female; median age: 67-years [range: 23-87]) underwent 18 PET/MRI scans. PET/MRI was performed at diagnosis (n = 4), at relapse (n = 7), or during remission (n = 7). Among the 18 scans, eight (44%) showed an inflammatory pattern and three (17%) a fibrous pattern; the other seven were normal. The distribution of the three patterns did not differ between patients with Takayasu arteritis (TA, n = 10 scans) and those with giant cell arteritis (GCA, n = 8 scans). PET/MRI findings were normal in 2/10 (20%) TA scans vs. 5/8 (62%) GCA scans (p = 0.3). Median SUV was 4.7 [2.1-8.6] vs. 2 [1.8-2.6] in patients with active disease vs. remission, respectively (p = 0.003). PET/MRI is a new hybrid imaging modality allowing comprehensive and multimodal analysis of vascular wall inflammation and the vascular lumen. This technique offers promising perspectives for the diagnosis and monitoring of LVV.

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Patrick Veit-Haibach, Irène Buvat, Ken Herrmann (2019 Jun 27)

EJNMMI supplement: bringing AI and radiomics to nuclear medicine.

European journal of nuclear medicine and molecular imaging : 2627-2629 : DOI : 10.1007/s00259-019-04395-4 En savoir plus
Résumé

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Anne-Ségolène Cottereau, Christophe Nioche, Anne-Sophie Dirand, Jérôme Clerc, Franck Morschhauser, Olivier Casasnovas, Michel Meignan, Irène Buvat (2019 Jun 16)

F-FDG PET Dissemination Features in Diffuse Large B-Cell Lymphoma Are Predictive of Outcome.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine : 40-45 : DOI : 10.2967/jnumed.119.229450 En savoir plus
Résumé

We assessed the predictive value of new radiomic features characterizing lesion dissemination in baseline F-FDG PET and tested whether combining them with baseline metabolic tumor volume (MTV) could improve prediction of progression-free survival (PFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. From the LNH073B trial (NCT00498043), patients with advanced-stage DLCBL and F-FDG PET/CT images available for review were selected. MTV and several radiomic features, including the distance between the 2 lesions that were farthest apart (Dmax), were calculated. Receiver-operating-characteristic analysis was used to determine the optimal cutoff for quantitative variables, and Kaplan-Meier survival analyses were performed. With a median age of 46 y, 95 patients were enrolled, half of them treated with R-CHOP biweekly (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and the other half with R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), with no significant impact on outcome. Median MTV and Dmax were 375 cm and 45 cm, respectively. The median follow-up was 44 mo. High MTV and Dmax were adverse factors for PFS ( = 0.027 and = 0.0003, respectively) and for OS ( = 0.0007 and = 0.0095, respectively). In multivariate analysis, only Dmax was significantly associated with PFS ( = 0.0014) whereas both factors remained significant for OS ( = 0.037 and = 0.0029, respectively). Combining MTV (>384 cm) and Dmax (>58 cm) yielded 3 risk groups for PFS ( = 0.0003) and OS ( = 0.0011): high with 2 adverse factors (4-y PFS and OS of 50% and 53%, respectively, = 18), low with no adverse factor (94% and 97%, = 36), and an intermediate category with 1 adverse factor (73% and 88%, = 41). Combining MTV with a parameter reflecting the tumor burden dissemination further improves DLBCL patient risk stratification at staging.

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Sylvain Auvity, Sébastien Goutal, Benoît Thézé, Catarina Chaves, Benoît Hosten, Bertrand Kuhnast, Wadad Saba, Raphaël Boisgard, Irène Buvat, Salvatore Cisternino, Nicolas Tournier (2019 Jun 10)

Corrigendum to « Evaluation of TSPO PET imaging, a marker of glial activation, to study the neuroimmune footprints of morphine exposure and withdrawal » [Drug Alcohol Depend. 170 (2017) 43-50].

Drug and alcohol dependence : 266-268 : DOI : S0376-8716(19)30162-0 En savoir plus
Résumé

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Fanny Orlhac, Frédérique Frouin, Christophe Nioche, Nicholas Ayache, Irène Buvat (2019 Jan 30)

Validation of A Method to Compensate Multicenter Effects Affecting CT Radiomics.

Radiology : 53-59 : DOI : 10.1148/radiol.2019182023 En savoir plus
Résumé

Background Radiomics extracts features from medical images more precisely and more accurately than visual assessment. However, radiomics features are affected by CT scanner parameters such as reconstruction kernel or section thickness, thus obscuring underlying biologically important texture features. Purpose To investigate whether a compensation method could correct for the variations of radiomic feature values caused by using different CT protocols. Materials and Methods Phantom data involving 10 texture patterns and 74 patients in cohorts 1 (19 men; 42 patients; mean age, 60.4 years; September-October 2013) and 2 (16 men; 32 patients; mean age, 62.1 years; January-September 2007) scanned by using different CT protocols were retrospectively included. For any radiomic feature, the compensation approach identified a protocol-specific transformation to express all data in a common space that were devoid of protocol effects. The differences in statistical distributions between protocols were assessed by using Friedman tests before and after compensation. Principal component analyses were performed on the phantom data to evaluate the ability to distinguish between texture patterns after compensation. Results In the phantom data, the statistical distributions of features were different between protocols for all radiomic features and texture patterns (P < .05). After compensation, the protocol effect was no longer detectable (P > .05). Principal component analysis demonstrated that each texture pattern was no longer displayed as different clusters corresponding to different imaging protocols, unlike what was observed before compensation. The correction for scanner effect was confirmed in patient data with 100% (10 of 10 features for cohort 1) and 98% (87 of 89 features for cohort 2) of P values less than .05 before compensation, compared with 30% (three of 10) and 15% (13 of 89) after compensation. Conclusion Image compensation successfully realigned feature distributions computed from different CT imaging protocols and should facilitate multicenter radiomic studies. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Steiger and Sood in this issue.

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Année de publication : 2018

Sébastien Goutal, Matthieu Gerstenmayer, Sylvain Auvity, Fabien Caillé, Sébastien Mériaux, Irène Buvat, Benoit Larrat, Nicolas Tournier (2018 Nov 12)

Physical blood-brain barrier disruption induced by focused ultrasound does not overcome the transporter-mediated efflux of erlotinib.

Journal of controlled release : official journal of the Controlled Release Society : 210-220 : DOI : S0168-3659(18)30646-1 En savoir plus
Résumé

Overcoming the efflux mediated by ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) remains a challenge for the delivery of small molecule tyrosine kinase inhibitors (TKIs) such as erlotinib to the brain. Inhibition of ABCB1 and ABCG2 at the mouse BBB improved the BBB permeation of erlotinib but could not be achieved in humans. BBB disruption induced by focused ultrasound (FUS) was investigated as a strategy to overcome the efflux transport of erlotinib in vivo. In rats, FUS combined with microbubbles allowed for a large and spatially controlled disruption of the BBB in the left hemisphere. ABCB1/ABCG2 inhibition was performed using elacridar (10 mg/kg i.v). The brain kinetics of erlotinib was studied using C-erlotinib Positron Emission Tomography (PET) imaging in 5 groups (n = 4-5 rats per group) including a baseline group, immediately after sonication (FUS), 48 h after FUS (FUS + 48 h), elacridar (ELA) and their combination (FUS + ELA). BBB integrity was assessed using the Evan’s Blue (EB) extravasation test. Brain exposure to C-erlotinib was measured as the area under the curve (AUC) of the brain kinetics (% injected dose (%ID) versus time (min)) in volumes corresponding to the disrupted (left) and the intact (right) hemispheres, respectively. EB extravasation highlighted BBB disruption in the left hemisphere of animals of the FUS and FUS + ELA groups but not in the control and ELA groups. EB extravasation was not observed 48 h after FUS suggesting recovery of BBB integrity. Compared with the control group (AUC = 1.4 ± 0.5%ID.min), physical BBB disruption did not impact the brain kinetics of C-erlotinib in the left hemisphere (p > .05) either immediately (AUC = 1.2 ± 0.1%ID.min) or 48 h after FUS (AUC = 1.1 ± 0.3%ID.min). Elacridar similarly increased C-erlotinib brain exposure to the left hemisphere in the absence (AUC = 2.2 ± 0.5%ID.min, p < .001) and in the presence of BBB disruption (AUC = 2.1 ± 0.5%ID.min, p < .001). AUC was never significantly different from AUC (p > .05), in any of the tested conditions. BBB integrity is not the rate limiting step for erlotinib delivery to the brain which is mainly governed by ABC-mediated efflux. Efflux transport of erlotinib persisted despite BBB disruption.

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Sarah Boughdad, Christophe Nioche, Fanny Orlhac, Laurine Jehl, Laurence Champion, Irène Buvat (2018 Aug 17)

Influence of age on radiomic features in F-FDG PET in normal breast tissue and in breast cancer tumors.

Oncotarget : 30855-30868 : DOI : 10.18632/oncotarget.25762 En savoir plus
Résumé

To help interpret measurements in breast tissue and breast tumors from F-FDG PET scans, we studied the influence of age in measurements of PET parameters in normal breast tissue and in a breast cancer (BC) population.

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Sylvain Reuzé, Antoine Schernberg, Fanny Orlhac, Roger Sun, Cyrus Chargari, Laurent Dercle, Eric Deutsch, Irène Buvat, Charlotte Robert (2018 Aug 2)

Radiomics in Nuclear Medicine Applied to Radiation Therapy: Methods, Pitfalls, and Challenges.

International journal of radiation oncology, biology, physics : 1117-1142 : DOI : S0360-3016(18)30815-0 En savoir plus
Résumé

Radiomics is a recent area of research in precision medicine and is based on the extraction of a large variety of features from medical images. In the field of radiation oncology, comprehensive image analysis is crucial to personalization of treatments. A better characterization of local heterogeneity and the shape of the tumor, depicting individual cancer aggressiveness, could guide dose planning and suggest volumes in which a higher dose is needed for better tumor control. In addition, noninvasive imaging features that could predict treatment outcome from baseline scans could help the radiation oncologist to determine the best treatment strategies and to stratify patients as at low risk or high risk of recurrence. Nuclear medicine molecular imaging reflects information regarding biological processes in the tumor thanks to a wide range of radiotracers. Many studies involving F-fluorodeoxyglucose positron emission tomography suggest an added value of radiomics compared with the use of conventional PET metrics such as standardized uptake value for both tumor diagnosis and prediction of recurrence or treatment outcome. However, these promising results should not hide technical difficulties that still currently prevent the approach from being widely studied or clinically used. These difficulties mostly pertain to the variability of the imaging features as a function of the acquisition device and protocol, the robustness of the models with respect to that variability, and the interpretation of the radiomic models. Addressing the impact of the variability in acquisition and reconstruction protocols is needed, as is harmonizing the radiomic feature calculation methods, to ensure the reproducibility of studies in a multicenter context and their implementation in a clinical workflow. In this review, we explain the potential impact of positron emission tomography radiomics for radiation therapy and underline the various aspects that need to be carefully addressed to make the most of this promising approach.

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Christophe Nioche, Fanny Orlhac, Sarah Boughdad, Sylvain Reuzé, Jessica Goya-Outi, Charlotte Robert, Claire Pellot-Barakat, Michael Soussan, Frédérique Frouin, Irène Buvat (2018 Jul 1)

LIFEx: A Freeware for Radiomic Feature Calculation in Multimodality Imaging to Accelerate Advances in the Characterization of Tumor Heterogeneity.

Cancer research : 4786-4789 : DOI : 10.1158/0008-5472.CAN-18-0125 En savoir plus
Résumé

Textural and shape analysis is gaining considerable interest in medical imaging, particularly to identify parameters characterizing tumor heterogeneity and to feed radiomic models. Here, we present a free, multiplatform, and easy-to-use freeware called LIFEx, which enables the calculation of conventional, histogram-based, textural, and shape features from PET, SPECT, MR, CT, and US images, or from any combination of imaging modalities. The application does not require any programming skills and was developed for medical imaging professionals. The goal is that independent and multicenter evidence of the usefulness and limitations of radiomic features for characterization of tumor heterogeneity and subsequent patient management can be gathered. Many options are offered for interactive textural index calculation and for increasing the reproducibility among centers. The software already benefits from a large user community (more than 800 registered users), and interactions within that community are part of the development strategy. This study presents a user-friendly, multi-platform freeware to extract radiomic features from PET, SPECT, MR, CT, and US images, or any combination of imaging modalities. .

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Sylvain Auvity, Fabien Caillé, Solène Marie, Catriona Wimberley, Martin Bauer, Oliver Langer, Irène Buvat, Sébastien Goutal, Nicolas Tournier (2018 May 12)

P-Glycoprotein (ABCB1) Inhibits the Influx and Increases the Efflux of C-Metoclopramide Across the Blood-Brain Barrier: A PET Study on Nonhuman Primates.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine : 1609-1615 : DOI : 10.2967/jnumed.118.210104 En savoir plus
Résumé

PET imaging using radiolabeled avid substrates of the ATP-binding cassette (ABC) transporter P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of C-metoclopramide, as a model of a weak ABCB1 substrate, in nonhuman primates. The regional brain kinetics of a tracer dose of C-metoclopramide (298 ± 44 MBq) were assessed in baboons using PET without ( = 4) or with ( = 4) intravenous coinfusion of the ABCB1 inhibitor tariquidar (4 mg/kg/h). Metabolite-corrected arterial input functions were generated to estimate the regional volume of distribution (), as well as the influx () and efflux () rate constants, using a 1-tissue-compartment model. Modeling outcome parameters were correlated with image-derived parameters, that is, areas under the regional time-activity curves (AUCs) from 0 to 30 min and from 30 to 60 min (SUV⋅min) and the elimination slope (; min) from 30 to 60 min. Tariquidar significantly increased the brain distribution of C-metoclopramide ( = 4.3 ± 0.5 mL/cm and 8.7 ± 0.5 mL/cm for baseline and ABCB1 inhibition conditions, respectively, < 0.001), with a 1.28-fold increase in ( < 0.05) and a 1.64-fold decrease in ( < 0.001). The effect of tariquidar was homogeneous across different brain regions. The parameters most sensitive to ABCB1 inhibition were (2.02-fold increase) and AUC from 30 to 60 min (2.02-fold increase). correlated significantly ( < 0.0001) with AUC from 30 to 60 min ( = 0.95), with AUC from 0 to 30 min ( = 0.87), and with ( = 0.62). C-metoclopramide PET imaging revealed the relative importance of both the influx hindrance and the efflux enhancement components of ABCB1 in a relevant model of the human BBB. The overall impact of ABCB1 on drug delivery to the brain can be noninvasively estimated from image-derived outcome parameters without the need for an arterial input function.

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Duc-Loc Nguyen, Catriona Wimberley, Charles Truillet, Benoit Jego, Fabien Caillé, Géraldine Pottier, Raphaël Boisgard, Irène Buvat, Viviane Bouilleret (2018 Apr 20)

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows.

Epilepsia : 1234-1244 : DOI : 10.1111/epi.14083 En savoir plus
Résumé

Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS.

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Anne-Ségolène Cottereau, Irene Buvat, Salim Kanoun, Annibale Versari, Olivier Casasnovas, Stephane Chauvie, Jérôme Clerc, Andrea Gallamini, Michel Meignan (2018 Apr 14)

Is there an optimal method for measuring baseline metabolic tumor volume in diffuse large B cell lymphoma?

European journal of nuclear medicine and molecular imaging : 1463-1464 : DOI : 10.1007/s00259-018-4005-4 En savoir plus
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