Advanced signal processing methods in dynamic contrast enhanced magnetic resonance imaging

Tato dizertační práce představuje metodu zobrazování perfúze magnetickou rezonancí, jež je výkonným nástrojem v diagnostice, především v onkologii. Po ukončení sběru časové sekvence T1-váhovaných obrazů zaznamenávajících distribuci kontrastní látky v těle začíná fáze zpracování dat, která je předmětem této dizertace. Je zde představen teoretický základ fyziologických modelů a modelů akvizice pomocí magnetické rezonance a celý řetězec potřebný k vytvoření obrazů odhadu parametrů perfúze a mikrocirkulace v tkáni. Tato dizertační práce je souborem uveřejněných prací autora přispívajícím k rozvoji metodologie perfúzního zobrazování a zmíněného potřebného teoretického rozboru.This dissertation describes quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), which is a powerful tool in diagnostics, mainly in oncology. After a time series of T1-weighted images recording contrast-agent distribution in the body has been acquired, data processing phase follows. It is presented step by step in this dissertation. The theoretical background in physiological and MRI-acquisition modeling is described together with the estimation process leading to parametric maps describing perfusion and microcirculation properties of the investigated tissue on a voxel-by-voxel basis. The dissertation is divided into this theoretical analysis and a set of publications representing particular contributions of the author to DCE-MRI.

MITK-ModelFit: A generic open-source framework for model fits and their exploration in medical imaging -- design, implementation and application on the example of DCE-MRI

Many medical imaging techniques utilize fitting approaches for quantitative parameter estimation and analysis. Common examples are pharmacokinetic modeling in DCE MRI/CT, ADC calculations and IVIM modeling in diffusion-weighted MRI and Z-spectra analysis in chemical exchange saturation transfer MRI. Most available software tools are limited to a special purpose and do not allow for own developments and extensions. Furthermore, they are mostly designed as stand-alone solutions using external frameworks and thus cannot be easily incorporated natively in the analysis workflow. We present a framework for medical image fitting tasks that is included in MITK, following a rigorous open-source, well-integrated and operating system independent policy. Software engineering-wise, the local models, the fitting infrastructure and the results representation are abstracted and thus can be easily adapted to any model fitting task on image data, independent of image modality or model. Several ready-to-use libraries for model fitting and use-cases, including fit evaluation and visualization, were implemented. Their embedding into MITK allows for easy data loading, pre- and post-processing and thus a natural inclusion of model fitting into an overarching workflow. As an example, we present a comprehensive set of plug-ins for the analysis of DCE MRI data, which we validated on existing and novel digital phantoms, yielding competitive deviations between fit and ground truth. Providing a very flexible environment, our software mainly addresses developers of medical imaging software that includes model fitting algorithms and tools. Additionally, the framework is of high interest to users in the domain of perfusion MRI, as it offers feature-rich, freely available, validated tools to perform pharmacokinetic analysis on DCE MRI data, with both interactive and automatized batch processing workflows.Comment: 31 pages, 11 figures URL: http://mitk.org/wiki/MITK-ModelFi

A Semi-parametric Technique for the Quantitative Analysis of Dynamic Contrast-enhanced MR Images Based on Bayesian P-splines

Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) is an important tool for detecting subtle kinetic changes in cancerous tissue. Quantitative analysis of DCE-MRI typically involves the convolution of an arterial input function (AIF) with a nonlinear pharmacokinetic model of the contrast agent concentration. Parameters of the kinetic model are biologically meaningful, but the optimization of the non-linear model has significant computational issues. In practice, convergence of the optimization algorithm is not guaranteed and the accuracy of the model fitting may be compromised. To overcome this problems, this paper proposes a semi-parametric penalized spline smoothing approach, with which the AIF is convolved with a set of B-splines to produce a design matrix using locally adaptive smoothing parameters based on Bayesian penalized spline models (P-splines). It has been shown that kinetic parameter estimation can be obtained from the resulting deconvolved response function, which also includes the onset of contrast enhancement. Detailed validation of the method, both with simulated and in vivo data, is provided

Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence

Purpose of this study was to evaluate the diagnostic performance of T1 relaxation time (T1) for differentiating prostate cancer (PCa) from benign tissue as well as high- from low-grade PCa. Twenty-three patients with suspicion for PCa were included in this prospective study. 3 T MRI including a Modified Look-Locker inversion recovery sequence was acquired. Subsequent targeted and systematic prostate biopsy served as a reference standard. T1 and apparent diffusion coefficient (ADC) value in PCa and reference regions without malignancy as well as high- and low-grade PCa were compared using the Mann-Whitney U test. The performance of T1, ADC value, and a combination of both to differentiate PCa and reference regions was assessed by receiver operating characteristic (ROC) analysis. T1 and ADC value were lower in PCa compared to reference regions in the peripheral and transition zone (p < 0.001). ROC analysis revealed high AUCs for T1 (0.92; 95%-CI, 0.87-0.98) and ADC value (0.97; 95%-CI, 0.94 to 1.0) when differentiating PCa and reference regions. A combination of T1 and ADC value yielded an even higher AUC. The difference was statistically significant comparing it to the AUC for ADC value alone (p = 0.02). No significant differences were found between high- and low-grade PCa for T1 (p = 0.31) and ADC value (p = 0.8). T1 relaxation time differs significantly between PCa and benign prostate tissue with lower T1 in PCa. It could represent an imaging biomarker for PCa

Analysis of DCE-MRI Data using a Nonnegative Elastic Net

We present a nonnegative Elastic Net approach for the analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging data. A multi-compartment approach is considered, which is translated into a (restricted) least square model selection problem. This is done by using a set of basis functions for a given set of candidate rate constants. The form of the basis functions is derived from a kinetic model and thus describes the contribution of some compartment. Using the Elastic Net estimator, we chose clusters of basis functions, and hence, rate constants of compartments. As further challenge, the estimator has to be restricted to positive regression parameters, which correspond to transfer rates of the compartments. The proposed estimation method is applied to an in-vivo data set

Spatially regularized estimation for the analysis of DCE-MRI data

Competing compartment models of different complexities have been used for the quantitative analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging data. We present a spatial Elastic Net approach that allows to estimate the number of compartments for each voxel such that the model complexity is not fixed a priori. A multi-compartment approach is considered, which is translated into a restricted least square model selection problem. This is done by using a set of basis functions for a given set of candidate rate constants. The form of the basis functions is derived from a kinetic model and thus describes the contribution of a specific compartment. Using a spatial Elastic Net estimator, we chose a sparse set of basis functions per voxel, and hence, rate constants of compartments. The spatial penalty takes into account the voxel structure of an image and performs better than a penalty treating voxels independently. The proposed estimation method is evaluated for simulated images and applied to an in-vivo data set

Maximum Entropy Technique and Regularization Functional for Determining the Pharmacokinetic Parameters in DCE-MRI

This paper aims to solve the arterial input function (AIF) determination in dynamic contrast-enhanced MRI (DCE-MRI), an important linear ill-posed inverse problem, using the maximum entropy technique (MET) and regularization functionals. In addition, estimating the pharmacokinetic parameters from a DCE-MR image investigations is an urgent need to obtain the precise information about the AIF-the concentration of the contrast agent on the left ventricular blood pool measured over time. For this reason, the main idea is to show how to find a unique solution of linear system of equations generally in the form of y = Ax + b, named an ill-conditioned linear system of equations after discretization of the integral equations, which appear in different tomographic image restoration and reconstruction issues. Here, a new algorithm is described to estimate an appropriate probability distribution function for AIF according to the MET and regularization functionals for the contrast agent concentration when applying Bayesian estimation approach to estimate two different pharmacokinetic parameters. Moreover, by using the proposed approach when analyzing simulated and real datasets of the breast tumors according to pharmacokinetic factors, it indicates that using Bayesian inference-that infer the uncertainties of the computed solutions, and specific knowledge of the noise and errors-combined with the regularization functional of the maximum entropy problem, improved the convergence behavior and led to more consistent morphological and functional statistics and results. Finally, in comparison to the proposed exponential distribution based on MET and Newton's method, or Weibull distribution via the MET and teaching-learning-based optimization (MET/TLBO) in the previous studies, the family of Gamma and Erlang distributions estimated by the new algorithm are more appropriate and robust AIFs

Quantifying Tumor Vascular Heterogeneity with Dynamic Contrast-Enhanced Magnetic Resonance Imaging: A Review

Tumor microvasculature possesses a high degree of heterogeneity in its structure and function. These features have been demonstrated to be important for disease diagnosis, response assessment, and treatment planning. The exploratory efforts of quantifying tumor vascular heterogeneity with DCE-MRI have led to promising results in a number of studies. However, the methodological implementation in those studies has been highly variable, leading to multiple challenges in data quality and comparability. This paper reviews several heterogeneity quantification methods, with an emphasis on their applications on DCE-MRI pharmacokinetic parametric maps. Important methodological and technological issues in experimental design, data acquisition, and analysis are also discussed, with the current opportunities and efforts for standardization highlighted

Spatial two tissue compartment model for DCE-MRI

In the quantitative analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) compartment models allow to describe the uptake of contrast medium with biological meaningful kinetic parameters. As simple models often fail to adequately describe the observed uptake behavior, more complex compartment models have been proposed. However, the nonlinear regression problem arising from more complex compartment models often suffers from parameter redundancy. In this paper, we incorporate spatial smoothness on the kinetic parameters of a two tissue compartment model by imposing Gaussian Markov random field priors on them. We analyse to what extent this spatial regularisation helps to avoid parameter redundancy and to obtain stable parameter estimates. Choosing a full Bayesian approach, we obtain posteriors and point estimates running Markov Chain Monte Carlo simulations. The proposed approach is evaluated for simulated concentration time curves as well as for in vivo data from a breast cancer study

Pharmacokinetic Analysis of Gd-DTPA Enhancement in dynamic three-dimensional MRI of breast lesions

The purpose of this study was to demonstrate that dynamic MRI covering both breasts can provide sensitivity for tumor detection as well as specificity and sensitivity for differentiation of tumor malignancy. Three-dimensional gradient echo scans were used covering both breasts. Before Gd-DTPA bolus injection, two scans were obtained with different flip angles, and after injection, a dynamic series followed. Thirty-two patients were scanned according to this protocol. From these scans, in addition to enhancement, the value of T1 before injection was obtained. This was used to estimate the concentration of Gd-DTPA as well as the pharmacokinetic parameters governing its time course. Signal enhancement in three-dimensional dynamic scanning was shown to be a sensitive basis for detection of tumors. In our series, all but two mam-mographically suspicious lesions did enhance, and in three cases, additional enhancing lesions were found, two of which were in the contralateral breast. The parameter most suited for classification of breast lesions into benign or malignant was shown to be the pharmacokinetically defined permeability k31, which, for that test, gave a sensitivity of 92% and a specificity of 70%. Our three-dimensional dynamic MRI data are sensitive for detection of mammographically occult breast tumors and specific for classification of these as benign or malignant