A multifractal approach to space-filling recovery for PET quantification.

Purpose: A new image-based methodology is developed for estimating the apparent space-filling properties of an object of interest in PET imaging without need for a robust segmentation step and used to recover accurate estimates of total lesion activity (TLA). Methods: A multifractal approach and the fractal dimension are proposed to recover the apparent space-filling index of a lesion (tumor volume, TV) embedded in nonzero background. A practical implementation is proposed, and the index is subsequently used with mean standardized uptake value (SUVmean) to correct TLA estimates obtained from approximate lesion contours. The methodology is illustrated on fractal and synthetic objects contaminated by partial volume effects (PVEs), validated on realistic 18F-fluorodeoxyglucose PET simulations and tested for its robustness using a clinical 18F-fluorothymidine PET test-retest dataset. Results: TLA estimates were stable for a range of resolutions typical in PET oncology (4-6 mm). By contrast, the space-filling index and intensity estimates were resolution dependent. TLA was generally recovered within 15% of ground truth on postfiltered PET images affected by PVEs. Volumes were recovered within 15% variability in the repeatability study. Results indicated that TLA is a more robust index than other traditional metrics such as SUVmean or TV measurements across imaging protocols. Conclusions: The fractal procedure reported here is proposed as a simple and effective computational alternative to existing methodologies which require the incorporation of image preprocessing steps (i.e., partial volume correction and automatic segmentation) prior to quantification

Methodological considerations in quantification of oncological FDG PET studies

Contains fulltext : 87741.pdf (publisher's version ) (Closed access) Contains fulltext : 87741-1.pdf (postprint version ) (Open Access)PURPOSE: This review aims to provide insight into the factors that influence quantification of glucose metabolism by FDG PET images in oncology as well as their influence on repeated measures studies (i.e. treatment response assessment), offering improved understanding both for clinical practice and research. METHODS: Structural PubMed searches have been performed for the many factors affecting quantification of glucose metabolism by FDG PET. Review articles and references lists have been used to supplement the search findings. RESULTS: Biological factors such as fasting blood glucose level, FDG uptake period, FDG distribution and clearance, patient motion (breathing) and patient discomfort (stress) all influence quantification. Acquisition parameters should be adjusted to maximize the signal to noise ratio without exposing the patient to a higher than strictly necessary radiation dose. This is especially challenging in pharmacokinetic analysis, where the temporal resolution is of significant importance. The literature is reviewed on the influence of attenuation correction on parameters for glucose metabolism, the effect of motion, metal artefacts and contrast agents on quantification of CT attenuation-corrected images. Reconstruction settings (analytical versus iterative reconstruction, post-reconstruction filtering and image matrix size) all potentially influence quantification due to artefacts, noise levels and lesion size dependency. Many region of interest definitions are available, but increased complexity does not necessarily result in improved performance. Different methods for the quantification of the tissue of interest can introduce systematic and random inaccuracy. CONCLUSIONS: This review provides an up-to-date overview of the many factors that influence quantification of glucose metabolism by FDG PET.01 juli 201

IMAGE PROCESSING, SEGMENTATION AND MACHINE LEARNING MODELS TO CLASSIFY AND DELINEATE TUMOR VOLUMES TO SUPPORT MEDICAL DECISION

Techniques for processing and analysing images and medical data have become the main’s translational applications and researches in clinical and pre-clinical environments. The advantages of these techniques are the improvement of diagnosis accuracy and the assessment of treatment response by means of quantitative biomarkers in an efficient way. In the era of the personalized medicine, an early and efficacy prediction of therapy response in patients is still a critical issue. In radiation therapy planning, Magnetic Resonance Imaging (MRI) provides high quality detailed images and excellent soft-tissue contrast, while Computerized Tomography (CT) images provides attenuation maps and very good hard-tissue contrast. In this context, Positron Emission Tomography (PET) is a non-invasive imaging technique which has the advantage, over morphological imaging techniques, of providing functional information about the patient’s disease. In the last few years, several criteria to assess therapy response in oncological patients have been proposed, ranging from anatomical to functional assessments. Changes in tumour size are not necessarily correlated with changes in tumour viability and outcome. In addition, morphological changes resulting from therapy occur slower than functional changes. Inclusion of PET images in radiotherapy protocols is desirable because it is predictive of treatment response and provides crucial information to accurately target the oncological lesion and to escalate the radiation dose without increasing normal tissue injury. For this reason, PET may be used for improving the Planning Treatment Volume (PTV). Nevertheless, due to the nature of PET images (low spatial resolution, high noise and weak boundary), metabolic image processing is a critical task. The aim of this Ph.D thesis is to develope smart methodologies applied to the medical imaging field to analyse different kind of problematic related to medical images and data analysis, working closely to radiologist physicians. Various issues in clinical environment have been addressed and a certain amount of improvements has been produced in various fields, such as organs and tissues segmentation and classification to delineate tumors volume using meshing learning techniques to support medical decision. In particular, the following topics have been object of this study: • Technique for Crohn’s Disease Classification using Kernel Support Vector Machine Based; • Automatic Multi-Seed Detection For MR Breast Image Segmentation; • Tissue Classification in PET Oncological Studies; • KSVM-Based System for the Definition, Validation and Identification of the Incisinal Hernia Reccurence Risk Factors; • A smart and operator independent system to delineate tumours in Positron Emission Tomography scans; 3 • Active Contour Algorithm with Discriminant Analysis for Delineating Tumors in Positron Emission Tomography; • K-Nearest Neighbor driving Active Contours to Delineate Biological Tumor Volumes; • Tissue Classification to Support Local Active Delineation of Brain Tumors; • A fully automatic system of Positron Emission Tomography Study segmentation. This work has been developed in collaboration with the medical staff and colleagues at the: • Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi (DIBIMED), University of Palermo • Cannizzaro Hospital of Catania • Istituto di Bioimmagini e Fisiologia Molecolare (IBFM) Centro Nazionale delle Ricerche (CNR) of Cefalù • School of Electrical and Computer Engineering at Georgia Institute of Technology The proposed contributions have produced scientific publications in indexed computer science and medical journals and conferences. They are very useful in terms of PET and MRI image segmentation and may be used daily as a Medical Decision Support Systems to enhance the current methodology performed by healthcare operators in radiotherapy treatments. The future developments of this research concern the integration of data acquired by image analysis with the managing and processing of big data coming from a wide kind of heterogeneous sources

Parametric imaging of FET PET using nonlinear based fitting

Tese de mestrado integrado em Engenharia Biomédica e Biofísica , apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016A importância do uso de aminoácidos marcados com isótopos radioativos em estudos de Tomografia de Emissão de Positrões (PET) tem sido amplamente demonstrada. Dentro deste grupo de traçadores, a metionina marcada com 11C tem sido o mais estudado. No entanto, a curta semi-vida do radioisótopo 11C tem levado ao desenvolvimento de marcadores análogos. Os marcadores com o radioisótopo 18F revelam-se os mais promissores para deteção de tumores no cérebro. Mais especificamente, o marcador O-(2-18F-Fluoroetil)-L-tirosina (FET) provou ser de grande importância na determinação da dimensão de tumores cerebrais e dos locais onde realizar a biopsia, no planeamento do tratamento a aplicar, e na deteção de recorrências. Foi também demonstrado que a forma como o FET é metabolizado ao longo do tempo depende do grau do tumor em estudo. Em gliomas de alto grau (HGG), a taxa de captação do FET é caracterizada por um pico inicial, seguido de uma diminuição da captação de FET, enquanto que em gliomas de baixo-grau (LGG) a taxa de captação do marcador tem um aumento contínuo ao longo do tempo. O presente estudo contou com 11 pacientes (3 mulheres, 8 homens, idade: 45 ± 15 anos) com tumores cerebrais primários não tratados confirmados por histologia. Seis pacientes foram diagnosticados com HGG, enquanto os restantes 5 foram diagnosticados com LGG. Os dados de PET foram adquiridos com o PET Insert do sistema híbrido Siemens 3T MR-BrainPET. As imagens foram segmentadas de forma a extrair apenas o volume correspondente ao tumor. Após a segmentação, calculou-se a média das curvas de tempo-atividade (TAC) dos volumes tumorais segmentados (STVs), e foram usados métodos de regressão linear e não linear para fazer o ajuste à TAC de cada volume. Para calcular os ajustes com o modelo linear, foram descartados os primeiros 5 minutos de aquisição. Os ajustes baseados na regressão não-linear foram aplicados à TAC correspondente à média entre os 2 e os 60 minutos de aquisição após a injeção. As imagens dos parâmetros foram calculadas a partir dos ajustes baseados na regressão não linear e aplicados a cada voxel. Foram testados três modelos não lineares diferentes: um modelo linear amortecido exponencialmente, um modelo linear amortecido exponencialmente e com um offset, e um modelo linear amortecido exponencialmente com o tempo dependente da raiz quadrada. Dos ajustes não lineares, foram extraídos dois parâmetros: a amplitude, A, e o parâmetro κ. De seguida, geraram-se as imagens dos parâmetros calculados sobre uma área tridimensional selecionada manualmente e contendo o tumor. Para tal, além dos três modelos não lineares, utilizou-se também o modelo linear, de modo a permitir uma comparação entre os diferentes métodos. No caso dos ajustes lineares, os parâmetros extraídos foram a ordenada na origem e o declive. Calcularam-se também as imagens dos parâmetros da regressão não linear usando o modelo linear amortecido exponencialmente com o tempo dependente da raiz quadrada para a cabeça inteira. Os modelos não-lineares foram mais precisos na reprodução das curvas de FET. Os modelos mais robustos foram os modelos lineares exponencialmente amortecidos sem offset. Nos ajustes aplicados à TAC média dos STVs, o modelo linear amortecido exponencialmente com o tempo dependente da raiz quadrada provou ser o que reproduz mais precisamente os dados, com valores de 2 entre 0,94 e 1,00. O parâmetro A do modelo linear amortecido exponencialmente com o tempo dependente da raiz quadrada foi o único que revelou uma diferença significativa entre HGG e LGG (p-value= 0.04, α=0.05). Ao gerar imagens paramétricas com base nos ajustes aplicados a cada voxel, os modelos de regressão não-linear com 2 parâmetros tiveram o melhor desempenho, com valores de 2 perto de 1. Combinando as imagens do parâmetro amplitude e as imagens da atividade total ao longo do tempo, foi possível distinguir entre graus tumorais. Os LGGs assumem valores de amplitude próximos dos valores do tecido saudável à sua volta, e por isso “desaparecem” da imagem paramétrica da amplitude. No caso dos HGGs, a imagem da amplitude reproduz a atividade no tumor. Os ajustes realizados com base na regressão linear devolveram valores de 2 próximos de zero, quer no caso dos STVs, quer no cálculo das imagens paramétricas. A distinção entre HGG e LGG é possível com base nas imagens paramétricas do declive, com os LGGs a assumirem valores de declive superiores aos do tecido saudável adjacente. Com os HGGs, a situação é a oposta: os valores do declive no tumor são inferiores aos do tecido saudável que o rodeia. Em geral, os modelos não lineares reproduzem melhor os dados provenientes de FET PET, mas a distinção entre HGG e LGG baseada num parâmetro apenas é melhor conseguida através de regressão linear. No entanto, a distinção entre HGG e LGG também é possível analisando simultaneamente as imagens dos parâmetros A e κ.The importance of radiolabeled amino acids in Positron Emission Tomography (PET) imaging of the brain has been demonstrated by several studies. The most well studied amino acid tracer is 11C-metionine, but because of the short half-life of 11C, 18F-labeled amino acid analogues have been developed for tumour imaging. A number of studies have proven the importance of O-(2-18F-Fluoroethyl)-L-tyrosine (FET) in determining the extent of cerebral gliomas, biopsy guidance, treatment planning, and detecting recurrence of brain tumours. It was also demonstrated that dynamic changes of FET accumulation in gliomas are variable. High-grade gliomas (HGG) are characterized by an early peak, followed by decrease of FET uptake, whereas the uptake in low-grade gliomas (LGG) steadily increases. Eleven patients (3 female, 8 male, age: 45±15 years) with untreated primary brain tumours and histopathologic confirmation were studied. Six patients had HGG, while the remaining 5 were diagnosed with LGG. PET acquisition was done with the PET Insert of a hybrid Siemens 3T MR-BrainPET system. For tumour volume fitting, a segmentation procedure was applied. After segmentation, the mean time-activity curve (TAC) of the segmented tumour volumes (STVs) was calculated. Linear and nonlinear regression were used to fit to the TAC of each volume. When performing the fits with the linear model, the first 5 minutes of acquisition were discarded. For the nonlinear regression, the fits were applied to the mean TAC from 2 to 60 minutes after injection. Parametric images were calculated based on nonlinear regression fitting of FET data in each voxel. Three different nonlinear models were tested: an exponentially damped linear model, an exponentially damped linear model with an offset, and an exponentially damped linear model with square-root time dependence. The considered nonlinear model parameters were amplitude, A, and κ. The parametric images of manually selected tridimensional volumes containing the tumour were generated. Linear regression based parametric images were also computed for comparison, and the assessed parameters were intercept and slope. Whole-head parametric images were calculated based on nonlinear regression fitting using the exponentially damped linear model with square-root time dependence. Nonlinear regression models were more accurate at reproducing FET TAC characteristics. The most robust models are the exponentially damped linear models without offset. For mean TAC fitting, a model with square-root time dependence reproduced FET activity curves more accurately, with coefficient of determination (2) values between 0.94 and 1.00. The A parameter from the exponentially damped linear model with square-root time dependence was the only one significantly different between HGG and LGG (p-value= 0.04, α=0.05). When generating parametric images based on voxel-wise fit, the nonlinear regression models with 2 parameters performed the best, with 2 close to 1. Visual distinction between tumour grades was possible by comparing the amplitude images with the images of the summed activity across time. In the amplitude, LGGs take values similar to the ones of the surrounding background, thus disappearing from the image. On the other hand, HGGs amplitude images reproduce tumour uptake. Linear regression model fits returned 2 values that were close to zero in both mean TAC fitting, and parametric image calculation. Grade distinction was possible based on the slope parameter alone, with LGGs showing higher slope values than the neighbouring tissue, and HGGs showing lower slope values than their surroundings. In general, though nonlinear models reproduce FET time activity curves more accurately, the distinction between low-grade and high-grade tumours based on one parameter only is better achieved by using linear regression model fitting. However, a reliable differentiation seems to be possible with joint analysis of A and κ parametric images

Postprocessing Neuroimaging methods in MRI and PET/MRI with applications to Multiple Sclerosis and other Neurological diseases

Many non-invasive imaging instruments have been developed in the last 40 years, allowing to obtain images of the interior human body while the patient is still alive. In the contest of Neurology studies, imaging system as CT, MRI, SPECT or PET allows to obtain biomarkers useful to quantitatively distinguish between healthy and unhealthy subjects, evaluate the staging of a Neurological illness in a patient, evaluate the efficacy of a treatment, explore the causes of the illness. In this work MRI and PET imaging system introduced from scratch, going from reconstruction from raw data to state-of-the art post-processing techniques and the computation of more popular biomarkers. After these introduction, three original work using the recent PET/MRI imaging system are presented, with a particular focus on the methods. These three studies involve patients with Multiple Sclerosis, Alzheimer's Disease and Brain Tumor