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Sci Rep ; 10(1): 9407, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32523075


The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for 18F-Fluciclovine PET and multisequence multiparametric MRI in the prediction of prostate cancer (PCa) aggressiveness, defined by Gleason Grade Group (GGG). 21 patients with PCa underwent PET/CT, PET/MRI and MRI before prostatectomy. DWI was post-processed using kurtosis (ADCk, K), mono- (ADCm), and biexponential functions (f, Dp, Df) while Logan plots were used to calculate volume of distribution (VT). In total, 16 unique PET (VT, SUV) and MRI derived quantitative parameters were evaluated. Univariate and multivariate analysis were carried out to estimate the potential of the quantitative parameters and their combinations to predict GGG 1 vs >1, using logistic regression with a nested leave-pair out cross validation (LPOCV) scheme and recursive feature elimination technique applied for feature selection. The second order rotating frame imaging (RAFF), monoexponential and kurtosis derived parameters had LPOCV AUC in the range of 0.72 to 0.92 while the corresponding value for VT was 0.85. The best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and 18F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of 18F-FACBC PET derived parameters (VT, SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.

PLoS One ; 14(7): e0217702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283771


PURPOSE: To develop and validate a classifier system for prediction of prostate cancer (PCa) Gleason score (GS) using radiomics and texture features of T2-weighted imaging (T2w), diffusion weighted imaging (DWI) acquired using high b values, and T2-mapping (T2). METHODS: T2w, DWI (12 b values, 0-2000 s/mm2), and T2 data sets of 62 patients with histologically confirmed PCa were acquired at 3T using surface array coils. The DWI data sets were post-processed using monoexponential and kurtosis models, while T2w was standardized to a common scale. Local statistics and 8 different radiomics/texture descriptors were utilized at different configurations to extract a total of 7105 unique per-tumor features. Regularized logistic regression with implicit feature selection and leave pair out cross validation was used to discriminate tumors with 3+3 vs >3+3 GS. RESULTS: In total, 100 PCa lesions were analysed, of those 20 and 80 had GS of 3+3 and >3+3, respectively. The best model performance was obtained by selecting the top 1% features of T2w, ADCm and K with ROC AUC of 0.88 (95% CI of 0.82-0.95). Features from T2 mapping provided little added value. The most useful texture features were based on the gray-level co-occurrence matrix, Gabor transform, and Zernike moments. CONCLUSION: Texture feature analysis of DWI, post-processed using monoexponential and kurtosis models, and T2w demonstrated good classification performance for GS of PCa. In multisequence setting, the optimal radiomics based texture extraction methods and parameters differed between different image types.

Interpretação de Imagem Assistida por Computador , Aprendizado de Máquina , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Humanos , Masculino , Pessoa de Meia-Idade
J Am Heart Assoc ; 7(20): e010378, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30371266


Background The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of mRNA , protein, and metabolite changes in the neonatal heart for identification of metabolism-related mechanisms associated with cardiac regeneration. Methods and Results Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with RNA sequencing and global proteomics and metabolomics. Gene ontology analysis, KEGG pathway analysis, and fuzzy c-means clustering were used to identify up- or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547 mRNA s and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS ( HMG -CoA [hydroxymethylglutaryl-coenzyme A] synthase)-mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of HMGCS in primary neonatal cardiomyocytes reduced the percentage of BrdU-positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle. Conclusions This study is the first systems-level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies.

Coração/crescimento & desenvolvimento , Camundongos/crescimento & desenvolvimento , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Ácidos Graxos/metabolismo , Expressão Gênica/fisiologia , Coração/embriologia , Ventrículos do Coração , Corpos Cetônicos/biossíntese , Metabolômica , Ácido Mevalônico/metabolismo , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/fisiologia , Transcriptoma/fisiologia
Anal Chem ; 90(7): 4832-4839, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29513001


Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 × (2) × 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing.

Corantes Fluorescentes/análise , Preparações Farmacêuticas/análise , Análise dos Mínimos Quadrados , Análise Espectral Raman , Fatores de Tempo
Magn Reson Med ; 77(3): 1249-1264, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-26924552


PURPOSE: To evaluate different fitting methods for intravoxel incoherent motion (IVIM) imaging of prostate cancer in the terms of repeatability and Gleason score prediction. METHODS: Eighty-one patients with histologically confirmed prostate cancer underwent two repeated 3 Tesla diffusion-weighted imaging (DWI) examinations performed using 14 b-values in the range of 0-500 s/mm2 and diffusion time of 19.004 ms. Mean signal intensities of regions-of-interest were fitted using five different fitting methods for IVIM as well as monoexponential, kurtosis, and stretched exponential models. The fitting methods and models were evaluated in the terms of fitting quality [Akaike information criteria (AIC)], repeatability, and Gleason score prediction. Tumors were classified into three groups (3 + 3, 3 + 4, > 3 + 4). Machine learning algorithms were used to evaluate the performance of the combined use of the parameters. Simulation studies were performed to evaluate robustness of the fitting methods against noise. RESULTS: Monoexponential model was preferred over IVIM based on AIC. The "pseudodiffusion" parameters demonstrated low repeatability and clinical value. Median "pseudodiffusion" fraction values were below 8.00%. Combined use of the parameters did not outperform the monoexponential model. CONCLUSION: Monoexponential model demonstrated the highest repeatability and clinical values in the regions-of-interest based analysis of prostate cancer DWI, b-values in the range of 0-500 s/mm2 . Magn Reson Med 77:1249-1264, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Artefatos , Imagem de Difusão por Ressonância Magnética/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Algoritmos , Simulação por Computador , Humanos , Aprendizado de Máquina , Masculino , Modelos Biológicos , Modelos Estatísticos , Movimento (Física) , Análise Numérica Assistida por Computador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Técnica de Subtração
Beilstein J Nanotechnol ; 5: 603-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24991496


Graphene, which as a new carbon material shows great potential for a range of applications because of its exceptional electronic and mechanical properties, becomes a matter of attention in these years. The use of graphene in nanoscale devices plays an important role in achieving more accurate and faster devices. Although there are lots of experimental studies in this area, there is a lack of analytical models. Quantum capacitance as one of the important properties of field effect transistors (FETs) is in our focus. The quantum capacitance of electrolyte-gated transistors (EGFETs) along with a relevant equivalent circuit is suggested in terms of Fermi velocity, carrier density, and fundamental physical quantities. The analytical model is compared with the experimental data and the mean absolute percentage error (MAPE) is calculated to be 11.82. In order to decrease the error, a new function of E composed of α and ß parameters is suggested. In another attempt, the ant colony optimization (ACO) algorithm is implemented for optimization and development of an analytical model to obtain a more accurate capacitance model. To further confirm this viewpoint, based on the given results, the accuracy of the optimized model is more than 97% which is in an acceptable range of accuracy.