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1.
J Nucl Med ; 65(4): 635-642, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38453361

RESUMO

The normalized distances from the hot spot of radiotracer uptake (SUVmax) to the tumor centroid (NHOC) and to the tumor perimeter (NHOP) have recently been suggested as novel PET features reflecting tumor aggressiveness. These biomarkers characterizing the shift of SUVmax toward the lesion edge during tumor progression have been shown to be prognostic factors in breast and non-small cell lung cancer (NSCLC) patients. We assessed the impact of imaging parameters on NHOC and NHOP, their complementarity to conventional PET features, and their prognostic value for advanced-NSCLC patients. Methods: This retrospective study investigated baseline [18F]FDG PET scans: cohort 1 included 99 NSCLC patients with no treatment-related inclusion criteria (robustness study); cohort 2 included 244 NSCLC patients (survival analysis) treated with targeted therapy (93), immunotherapy (63), or immunochemotherapy (88). Although 98% of patients had metastases, radiomic features including SUVs were extracted from the primary tumor only. NHOCs and NHOPs were computed using 2 approaches: the normalized distance from the localization of SUVmax or SUVpeak to the tumor centroid or perimeter. Bland-Altman analyses were performed to investigate the impact of both spatial resolution (comparing PET images with and without gaussian postfiltering) and image sampling (comparing 2 voxel sizes) on feature values. The correlation of NHOCs and NHOPs with other features was studied using Spearman correlation coefficients (r). The ability of NHOCs and NHOPs to predict overall survival (OS) was estimated using the Kaplan-Meier method. Results: In cohort 1, NHOC and NHOP features were more robust to image filtering and to resampling than were SUVs. The correlations were weak between NHOCs and NHOPs (r ≤ 0.45) and between NHOCs or NHOPs and any other radiomic features (r ≤ 0.60). In cohort 2, the patients with short OS demonstrated higher NHOCs and lower NHOPs than those with long OS. NHOCs significantly distinguished 2 survival profiles in patients treated with immunotherapy (log-rank test, P < 0.01), whereas NHOPs stratified patients regarding OS in the targeted therapy (P = 0.02) and immunotherapy (P < 0.01) subcohorts. Conclusion: Our findings suggest that even in advanced NSCLC patients, NHOC and NHOP features pertaining to the primary tumor have prognostic potential. Moreover, these features appeared to be robust with respect to imaging protocol parameters and complementary to other radiomic features and are now available in LIFEx software to be independently tested by others.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Prognóstico , Estudos Retrospectivos , Biomarcadores , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos
2.
Cancers (Basel) ; 12(7)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32709121

RESUMO

Developing precision medicine is a major trend in clinical oncology. The main adverse effects of ifosfamide, actinomycin D and vincristine (IVA) treatment for rhabdomyosarcoma are haematological toxicities such as neutropenia or thrombocytopenia. The severity of these effects vary among patients but their dynamic profiles are similar. A non-empirical adjustment of the chemotherapy dose to avoid severe toxicities could help secure the treatment administration. Twenty-four patients with rhabdomyosarcoma treated with IVA chemotherapy courses were selected. Before and during each cycle, routine multiple blood cell counts were performed allowing for a dynamic study of the haematological toxicities. We developed a machine learning analysis using a gradient boosting regression technique to forecast the ifosfamide induced haematological toxicities as a function of neutrophils and platelets initial levels and the initial ifosfamide dose. To validate models' accuracy, predicted and observed neutrophils and platelets levels were compared. The model was able to reproduce the dynamic profiles of the haematological toxicities. Among all cycles, the mean absolute errors between predicted and observed neutrophils and platelets levels were 1.0 and 72.8 G/L, respectively. Adjusting a patient's ifosfamide dose based upon the predicted haematological toxicity levels at the end of a treatment cycle could enable tailored treatment.

3.
EJNMMI Phys ; 5(1): 14, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29869186

RESUMO

BACKGROUND: Matched attenuation maps are vital for obtaining accurate and reproducible kinetic and static parameter estimates from PET data. With increased interest in PET/CT imaging of diffuse lung diseases for assessing disease progression and treatment effectiveness, understanding the extent of the effect of respiratory motion and establishing methods for correction are becoming more important. In a previous study, we have shown that using the wrong attenuation map leads to large errors due to density mismatches in the lung, especially in dynamic PET scans. Here, we extend this work to the case where the study is sub-divided into several scans, e.g. for patient comfort, each with its own CT (cine-CT and 'snap shot' CT). A method to combine multi-CT information into a combined-CT has then been developed, which averages the CT information from each study section to produce composite CT images with the lung density more representative of that in the PET data. This combined-CT was applied to nine patients with idiopathic pulmonary fibrosis, imaged with dynamic 18F-FDG PET/CT to determine the improvement in the precision of the parameter estimates. RESULTS: Using XCAT simulations, errors in the influx rate constant were found to be as high as 60% in multi-PET/CT studies. Analysis of patient data identified displacements between study sections in the time activity curves, which led to an average standard error in the estimates of the influx rate constant of 53% with conventional methods. This reduced to within 5% after use of combined-CTs for attenuation correction of the study sections. CONCLUSIONS: Use of combined-CTs to reconstruct the sections of a multi-PET/CT study, as opposed to using the individually acquired CTs at each study stage, produces more precise parameter estimates and may improve discrimination between diseased and normal lung.

4.
Biomed Opt Express ; 8(3): 1665-1681, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28663855

RESUMO

Application of nanotechnology for biomedicine in cancer therapy allows for direct delivery of anticancer agents to tumors. An example of such therapies is the nanoparticle-mediated near-infrared hyperthermia treatment. In order to investigate the influence of nanoparticle properties on the spatial distribution of heat in the tumor and healthy tissues, accurate simulations are required. The Geant4 Application for Emission Tomography (GATE) open-source simulation platform, based on the Geant4 toolkit, is widely used by the research community involved in molecular imaging, radiotherapy and optical imaging. We present an extension of GATE that can model nanoparticle-mediated hyperthermal therapy as well as simple heat diffusion in biological tissues. This new feature of GATE combined with optical imaging allows for the simulation of a theranostic scenario in which the patient is injected with theranostic nanosystems that can simultaneously deliver therapeutic (i.e. hyperthermia therapy) and imaging agents (i.e. fluorescence imaging).

5.
Phys Med Biol ; 63(1): 015007, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-29053106

RESUMO

PET/CT quantification of lung tissue is limited by several difficulties: the lung density and local volume changes during respiration, the anatomical mismatch between PET and CT and the relative contributions of tissue, air and blood to the PET signal (the tissue fraction effect). Air fraction correction (AFC) has been shown to improve PET image quantification in the lungs. Methods to correct for the movement and anatomical mismatch involve respiratory gating and image registration techniques. While conventional registration methods only account for spatial mismatch, the Jacobian determinant of the deformable registration transformation field can be used to estimate local volume changes and could therefore potentially be used to correct (i.e. Jacobian Correction, JC) the PET signal for changes in concentration due to local volume changes. This work aims to investigate the relationship between variations in the lung due to respiration, specifically density, tracer concentration and local volume changes. In particular, we study the effect of AFC and JC on PET quantitation after registration of respiratory gated PET/CT patient data. Six patients suffering from lung cancer with solitary pulmonary nodules underwent [Formula: see text]F-FDG PET/cine-CT. The PET data were gated into six respiratory gates using displacement gating based on a real-time position management (RPM) signal and reconstructed with matched gated CT. The PET tracer concentration and tissue density were extracted from registered gated PET and CT images before and after corrections (AFC or JC) and compared to the values from the reference images. Before correction, we observed a linear correlation between the PET tracer concentration values and density. Across all gates and patients, the maximum relative change in PET tracer concentration before (after) AFC was found to be 16.2% (4.1%) and the maximum relative change in tissue density and PET tracer concentration before (after) JC was found to be 17.1% (5.5%) and 16.2% (6.8%) respectively. Overall our results show that both AFC or JC largely explain the observed changes in PET tracer activity over the respiratory cycle. We also speculate that a second order effect is related to change in fluid content but this needs further investigation. Consequently, either AFC or JC is recommended when combining lung PET images from different gates to reduce noise.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Respiração , Técnicas de Imagem de Sincronização Respiratória/métodos , Humanos
6.
Phys Med Biol ; 61(8): 3148-63, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-27007013

RESUMO

Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant (18)F-FDG and (18)F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Respiração , Tórax/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Movimento (Física) , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos
7.
Phys Med Biol ; 61(22): 7975-7993, 2016 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-27779136

RESUMO

Positron emission tomography (PET) images are degraded by a phenomenon known as the partial volume effect (PVE). Approaches have been developed to reduce PVEs, typically through the utilisation of structural information provided by other imaging modalities such as MRI or CT. These methods, known as partial volume correction (PVC) techniques, reduce PVEs by compensating for the effects of the scanner resolution, thereby improving the quantitative accuracy. The PETPVC toolbox described in this paper comprises a suite of methods, both classic and more recent approaches, for the purposes of applying PVC to PET data. Eight core PVC techniques are available. These core methods can be combined to create a total of 22 different PVC techniques. Simulated brain PET data are used to demonstrate the utility of toolbox in idealised conditions, the effects of applying PVC with mismatched point-spread function (PSF) estimates and the potential of novel hybrid PVC methods to improve the quantification of lesions. All anatomy-based PVC techniques achieve complete recovery of the PET signal in cortical grey matter (GM) when performed in idealised conditions. Applying deconvolution-based approaches results in incomplete recovery due to premature termination of the iterative process. PVC techniques are sensitive to PSF mismatch, causing a bias of up to 16.7% in GM recovery when over-estimating the PSF by 3 mm. The recovery of both GM and a simulated lesion was improved by combining two PVC techniques together. The PETPVC toolbox has been written in C++, supports Windows, Mac and Linux operating systems, is open-source and publicly available.


Assuntos
Algoritmos , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Simulação por Computador , Humanos , Modelos Neurológicos
8.
Appl Radiat Isot ; 103: 15-24, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26046519

RESUMO

For a scintillator used for spectrometry, the generation, transport and detection of optical photons have a great impact on the energy spectrum resolution. A complete Monte Carlo model of a scintillator includes a coupled ionizing particle and optical photon transport, which can be simulated with the GEANT4 code. The GEANT4 surface parameters control the physics processes an optical photon undergoes when reaching the surface of a volume. In this work the impact of each surface parameter on the optical transport was studied by looking at the optical spectrum: the number of detected optical photons per ionizing source particle from a large plastic scintillator, i.e. the output signal. All simulations were performed using GATE v6.2 (GEANT4 Application for Tomographic Emission). The surface parameter finish (polished, ground, front-painted or back-painted) showed the greatest impact on the optical spectrum whereas the surface parameter σ(α), which controls the surface roughness, had a relatively small impact. It was also shown how the surface parameters reflectivity and reflectivity types (specular spike, specular lobe, Lambertian and backscatter) changed the optical spectrum depending on the probability for reflection and the combination of reflectivity types. A change in the optical spectrum will ultimately have an impact on a simulated energy spectrum. By studying the optical spectra presented in this work, a GEANT4 user can predict the shift in an optical spectrum caused be the alteration of a specific surface parameter.


Assuntos
Algoritmos , Modelos Estatísticos , Método de Monte Carlo , Fótons , Radiometria/métodos , Software , Simulação por Computador , Luz , Doses de Radiação , Radiação Ionizante , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e Especificidade , Propriedades de Superfície
9.
Phys Med Biol ; 60(18): 7387-402, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26350580

RESUMO

Recently, there has been an increased interest in imaging different pulmonary disorders using PET techniques. Previous work has shown, for static PET/CT, that air content in the lung influences reconstructed image values and that it is vital to correct for this 'tissue fraction effect' (TFE). In this paper, we extend this work to include the blood component and also investigate the TFE in dynamic imaging. CT imaging and PET kinetic modelling are used to determine fractional air and blood voxel volumes in six patients with idiopathic pulmonary fibrosis. These values are used to illustrate best and worst case scenarios when interpreting images without correcting for the TFE. In addition, the fractional volumes were used to determine correction factors for the SUV and the kinetic parameters. These were then applied to the patient images. The kinetic parameters K1 and Ki along with the static parameter SUV were all found to be affected by the TFE with both air and blood providing a significant contribution to the errors. Without corrections, errors range from 34-80% in the best case and 29-96% in the worst case. In the patient data, without correcting for the TFE, regions of high density (fibrosis) appeared to have a higher uptake than lower density (normal appearing tissue), however this was reversed after air and blood correction. The proposed correction methods are vital for quantitative and relative accuracy. Without these corrections, images may be misinterpreted.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Estudos de Casos e Controles , Simulação por Computador , Feminino , Humanos , Masculino
10.
J Biomed Opt ; 19(2): 026004, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24522804

RESUMO

The Geant4 Application for Emission Tomography (GATE) is an advanced open-source software dedicated to Monte-Carlo (MC) simulations in medical imaging involving photon transportation (Positron emission tomography, single photon emission computed tomography, computed tomography) and in particle therapy. In this work, we extend the GATE to support simulations of optical imaging, such as bioluminescence or fluorescence imaging, and validate it against the MC for multilayered media standard simulation tool for biomedical optics in simple geometries. A full simulation set-up for molecular optical imaging (bioluminescence and fluorescence) is implemented in GATE, and images of the light distribution emitted from a phantom demonstrate the relevance of using GATE for optical imaging simulations.


Assuntos
Simulação por Computador , Método de Monte Carlo , Imagem Óptica/métodos , Software , Tomografia/métodos , Modelos Biológicos , Imagens de Fantasmas , Reprodutibilidade dos Testes
11.
J Biomed Opt ; 18(11): 117010, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24247811

RESUMO

Optical properties of fresh and frozen tissues of rat heart, kidney, brain, liver, and muscle were measured in the 450- to 700-nm range. The total reflectance and transmittance were measured using a well-calibrated integral sphere set-up. Absorption coefficient µa and reduced scattering coefficient µ's were derived from the experimental measurements using the inverse adding doubling technique. The influence of cryogenic processing on optical properties was studied. Interindividual and intraindividual variations were assessed. These new data aim at filling the lack of validated optical properties in the visible range especially in the blue-green region of particular interest for fluorescence and optogenetics preclinical studies. Furthermore, we provide a unique comparison of the optical properties of different organs obtained using the same measurement set-up for fresh and frozen tissues as well as an estimate of the intraindividual and interindividual variability.


Assuntos
Criopreservação , Modelos Biológicos , Fenômenos Ópticos , Absorção , Animais , Química Encefálica/fisiologia , Simulação por Computador , Rim/química , Método de Monte Carlo , Músculos/química , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Espalhamento de Radiação
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