Texture analysis of multimodal magnetic resonance images in support of diagnostic classification of childhood brain tumours

Primary brain tumours are recognised as the most common form of solid tumours in children, with pilocytic astrocytoma, medulloblastoma and ependymoma being found most frequently. Despite their high mortality rate, early detection can be facilitated through the use of Magnetic Resonance Imaging (MRI), which is the preferred scanning technique for paediatric patients. MRI offers a variety of imaging sequences through structural and functional imaging, as well as providing complementary tissue information. However visual examination of MR images provides limited ability to characterise distinct histological types of brain tumours. In order to improve diagnostic classification, we explore the use of a computer-aided system based on texture analysis (TA) methods. TA has been applied on conventional MRI but has been less commonly studied on diffusion MRI of brain-related pathology. Furthermore, the combination of textural features derived from both imaging approaches has not yet been widely studied. In this thesis, the aim of the research is to investigate TA based on multi-centre multimodal MRI, in order to provide more comprehensive information and develop an automated processing framework for the classification of childhood brain tumours

Automated segmentation and characterisation of white matter hyperintensities

Neuroimaging has enabled the observation of damage to the white matter that occurs frequently in elderly population and is depicted as hyperintensities in specific magnetic resonance images. Since the pathophysiology underlying the existence of these signal abnormalities and the association with clinical risk factors and outcome is still investigated, a robust and accurate quantification and characterisation of these observations is necessary. In this thesis, I developed a data-driven split and merge model selection framework that results in the joint modelling of normal appearing and outlier observations in a hierarchical Gaussian mixture model. The resulting model can then be used to segment white matter hyperintensities (WMH) in a post-processing step. The validity of the method in terms of robustness to data quality, acquisition protocol and preprocessing and its comparison to the state of the art is evaluated in both simulated and clinical settings. To further characterise the lesions, a subject-specific coordinate frame that divides the WM region according to the relative distance between the ventricular surface and the cortical sheet and to the lobar location is introduced. This coordinate frame is used for the comparison of lesion distributions in a population of twin pairs and for the prediction and standardisation of visual rating scales. Lastly the cross-sectional method is extended into a longitudinal framework, in which a Gaussian Mixture model built on an average image is used to constrain the representation of the individual time points. The method is validated through a purpose-build longitudinal lesion simulator and applied to the investigation of the relationship between APOE genetic status and lesion load progression

Proceedings of the MICCAI Challenge on Multimodal Brain Tumor Image Segmentation (BRATS) 2013

International audienceBecause of their unpredictable appearance and shape, segmenting brain tumors from multi-modal imaging data is one of the most challenging tasks in medical image analysis. Although many different segmentation strategies have been proposed in the literature, it is hard to compare existing methods because the validation datasets that are used differ widely in terms of input data (structural MR contrasts; perfusion or diffusion data; ...), the type of lesion (primary or secondary tumors; solid or infiltratively growing), and the state of the disease (pre- or post-treatment). In order to gauge the current state-of-the-art in automated brain tumor segmentation and compare between different methods, we are organizing a Multimodal Brain Tumor Image Segmentation (BRATS) challenge that is held in conjunction with the 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2013) on September 22nd, 2013 in Nagoya, Japan

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

Characterization of alar ligament on 3.0T MRI: a cross-sectional study in IIUM Medical Centre, Kuantan

INTRODUCTION: The main purpose of the study is to compare the normal anatomy of alar ligament on MRI between male and female. The specific objectives are to assess the prevalence of alar ligament visualized on MRI, to describe its characteristics in term of its course, shape and signal homogeneity and to find differences in alar ligament signal intensity between male and female. This study also aims to determine the association between the heights of respondents with alar ligament signal intensity and dimensions. MATERIALS & METHODS: 50 healthy volunteers were studied on 3.0T MR scanner Siemens Magnetom Spectra using 2-mm proton density, T2 and fat-suppression sequences. Alar ligament is depicted in 3 planes and the visualization and variability of the ligament courses, shapes and signal intensity characteristics were determined. The alar ligament dimensions were also measured. RESULTS: Alar ligament was best depicted in coronal plane, followed by sagittal and axial planes. The orientations were laterally ascending in most of the subjects (60%), predominantly oval in shaped (54%) and 67% showed inhomogenous signal. No significant difference of alar ligament signal intensity between male and female respondents. No significant association was found between the heights of the respondents with alar ligament signal intensity and dimensions. CONCLUSION: Employing a 3.0T MR scanner, the alar ligament is best portrayed on coronal plane, followed by sagittal and axial planes. However, tremendous variability of alar ligament as depicted in our data shows that caution needs to be exercised when evaluating alar ligament, especially during circumstances of injury

Imaging and therapy in multiple sclerosis

Multiple sclerosis (MS) is a common, debilitating autoimmune disorder of the central nervous system (CNS). The most visible element of MS pathology is white matter (WM) lesions. However, extra-lesional abnormalities are recognised and appear most marked at the outer (subpial) brain surfaces at post-mortem. Magnetisation transfer ratio (MTR) is a non-conventional MRI sequence that correlates with myelin density and axonal count, and has recently uncovered reductions in the innermost (periventricular) layers and outermost (cortical) layers of patients with longstanding MS. These abnormalities are termed “outside-in” changes. The cause, extent, evolution and treatment-responsiveness of these outside-in gradients is unknown. Most patients present with relapsing-remitting (RR) MS for which numerous immunomodulatory disease-modifying therapies (DMTs) are licensed. However, after approximately 20 years most convert to secondary progressive (SP) MS where immunomodulatory therapies have little if any effect. Whether DMTs delay or prevent this transition remains unclear. During this PhD I examined whether outside-in MTR gradients occur in different disease stages, their clinical associations and predictive capabilities, and (for periventricular gradients) their response to a potent immunomodulatory DMT. In a separate project, I used real-world data to explore whether DMT use is associated with a lower risk of conversion to SPMS. Outside-in MTR gradients of tissue damage were seen in periventricular and cortical regions at all stages of relapse-onset MS and primary-progressive MS. The periventricular MTR gradient was reversed by peripheral immunomodulation and independently predicted subsequent relapse activity on and off DMTs. The underlying process(es) remain unknown but appear at least partially distinct from those underlying lesion formation; a CSF-mediated process – secondary to meningeal inflammation or primarily degenerative – might explain both periventricular and cortical gradients. Among patients with RRMS, initial treatment with fingolimod, natalizumab or alemtuzumab was associated with a lower risk of conversion to SPMS compared to initial treatment with glatiramer acetate or interferon beta over a median 5.8 years of follow-up. A lower risk of conversion was also associated with early (versus late) commencement of glatiramer acetate or interferon beta; and with early escalation from these therapies to fingolimod, natalizumab or alemtuzumab compared to late escalation. These findings, considered along with these therapies’ risks, may help inform decisions about DMT selection.Grand Charity of the Freemason

Advanced perfusion quantification methods for dynamic PET and MRI data modelling

The functionality of tissues is guaranteed by the capillaries, which supply the microvascular network providing a considerable surface area for exchanges between blood and tissues. Microcirculation is affected by any pathological condition and any change in the blood supply can be used as a biomarker for the diagnosis of lesions and the optimization of the treatment. Nowadays, a number of techniques for the study of perfusion in vivo and in vitro are available. Among the several imaging modalities developed for the study of microcirculation, the analysis of the tissue kinetics of intravenously injected contrast agents or tracers is the most widely used technique. Tissue kinetics can be studied using different modalities: the positive enhancement of the signal in the computed tomography and in the ultrasound dynamic contrast enhancement imaging; T1-weighted MRI or the negative enhancement of T2* weighted MRI signal for the dynamic susceptibility contrast imaging or, finally, the uptake of radiolabelled tracers in dynamic PET imaging. Here we will focus on the perfusion quantification of dynamic PET and MRI data. The kinetics of the contrast agent (or the tracer) can be analysed visually, to define qualitative criteria but, traditionally, quantitative physiological parameters are extracted with the implementation of mathematical models. Serial measurements of the concentration of the tracer (or of the contrast agent) in the tissue of interest, together with the knowledge of an arterial input function, are necessary for the calculation of blood flow or perfusion rates from the wash-in and/or wash-out kinetic rate constants. The results depend on the acquisition conditions (type of imaging device, imaging mode, frequency and total duration of the acquisition), the type of contrast agent or tracer used, the data pre-processing (motion correction, attenuation correction, correction of the signal into concentration) and the data analysis method. As for the MRI, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging technique that can be used to measure properties of tissue microvasculature. It is sensitive to differences in blood volume and vascular permeability that can be associated with tumour angiogenesis. DCE-MRI has been investigated for a range of clinical oncologic applications (breast, prostate, cervix, liver, lung, and rectum) including cancer detection, diagnosis, staging, and assessment of treatment response. Tumour microvascular measurements by DCE-MRI have been found to correlate with prognostic factors (such as tumour grade, microvessel density, and vascular endothelial growth factor expression) and with recurrence and survival outcomes. Furthermore, DCE-MRI changes measured during treatment have been shown to correlate with outcome, suggesting a role as a predictive marker. The accuracy of DCE-MRI relies on the ability to model the pharmacokinetics of an injected contrast agent using the signal intensity changes on sequential magnetic resonance images. DCE-MRI data are usually quantified with the application of the pharmacokinetic two-compartment Tofts model (also known as the standard model), which represents the system with the plasma and tissue (extravascular extracellular space) compartments and with the contrast reagent exchange rates between them. This model assumes a negligible contribution from the vascular space and considers the system in, what-is-known as, the fast exchange limit, assuming infinitely fast transcytolemmal water exchange kinetics. In general, the number, as well as any assumption about the compartments, depends on the properties of the contrast agent used (mainly gadolinium) together with the tissue physiology or pathology studied. For this reason, the choice of the model is crucial in the analysis of DCE-MRI data. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumours, head and neck tumours, primary and metastatic brain tumours, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. PET studies of tumours can be performed for several reasons including the quantification of tumour perfusion, the evaluation of tumour metabolism, the tracing of radiolabelled cytostatic agents. In particular, the kinetic analysis of PET imaging has showed, in the past few years, an increasing value in tumour diagnosis, as well as in tumour therapy, through providing additional indicative parameters. Many authors have showed the benefit of kinetic analysis of anticancer drugs after labelling with radionuclide in measuring the specific therapeutic effect bringing to light the feasibility of applying the kinetic analysis to the dynamic acquisition. Quantification methods can involve visual analysis together with compartmental modelling and can be applied to a wide range of different tracers. The increased glycolysis in the most malignancies makes 18F-FDG-PET the most common diagnostic method used in tumour imaging. But, PET metabolic alteration in the target tissue can depend by many other factors. For example, most types of cancer are characterized by increased choline transport and by the overexpression of choline kinase in highly proliferating cells in response to enhanced demand of phosphatidylcholine (prostate, breast, lung, ovarian and colon cancers). This effect can be diagnosed with choline-based tracers as the 18Ffluoromethylcholine (18F-FCH), or the even more stable 18F-D4-Choline. Cellular proliferation is also imaged with 18F-fluorothymidine (FLT), which is trapped within the cytosol after being mono phosphorylated by thymidine kinase-1 (TK1), a principal enzyme in the salvage pathway of DNA synthesis. 18F-FLT has been found to be useful for noninvasive assessment of the proliferation rate of several types of cancer and showed high reproducibility and accuracy in breast and lung cancer tumours. The aim of this thesis is the perfusion quantification of dynamic PET and MRI data of patients with lung, brain, liver, prostate and breast lesions with the application of advanced models. This study covers a wide range of imaging methods and applications, presenting a novel combination of MRI-based perfusion measures with PET kinetic modelling parameters in oncology. It assesses the applicability and stability of perfusion quantification methods, which are not currently used in the routine clinical practice. The main achievements of this work include: 1) the assessment of the stability of perfusion quantification of D4-Choline and 18F-FLT dynamic PET data in lung and liver lesions, respectively (first applications in the literature); 2) the development of a model selection in the analysis of DCE-MRI data of primary brain tumours (first application of the extended shutter speed model); 3) the multiparametric analysis of PET and MRI derived perfusion measurements of primary brain tumour and breast cancer together with the integration of immuohistochemical markers in the prediction of breast cancer subtype (analysis of data acquired on the hybrid PET/MRI scanner). The thesis is structured as follows: - Chapter 1 is an introductive chapter on cancer biology. Basic concepts, including the causes of cancer, cancer hallmarks, available cancer treatments, are described in this first chapter. Furthermore, there are basic concepts of brain, breast, prostate and lung cancers (which are the lesions that have been analysed in this work). - Chapter 2 is about Positron Emission Tomography. After a brief introduction on the basics of PET imaging, together with data acquisition and reconstruction methods, the chapter focuses on PET in the clinical settings. In particular, it shows the quantification techniques of static and dynamic PET data and my results of the application of graphical methods, spectral analysis and compartmental models on dynamic 18F-FDG, 18F-FLT and 18F-D4- Choline PET data of patients with breast, lung cancer and hepatocellular carcinoma. - Chapter 3 is about Magnetic Resonance Imaging. After a brief introduction on the basics of MRI, the chapter focuses on the quantification of perfusion weighted MRI data. In particular, it shows the pharmacokinetic models for the quantification of dynamic contrast enhanced MRI data and my results of the application of the Tofts, the extended Tofts, the shutter speed and the extended shutter speed models on a dataset of patients with brain glioma. - Chapter 4 introduces the multiparametric imaging techniques, in particular the combined PET/CT and the hybrid PET/MRI systems. The last part of the chapter shows the applications of perfusion quantification techniques on a multiparametric study of breast tumour patients, who simultaneously underwent DCE-MRI and 18F-FDG PET on a hybrid PET/MRI scanner. Then the results of a predictive study on the same dataset of breast tumour patients integrated with immunohistochemical markers. Furthermore, the results of a multiparametric study on DCE-MRI and 18F-FCM brain data acquired both on a PET/CT scanner and on an MR scanner, separately. Finally, it will show the application of kinetic analysis in a radiomic study of patients with prostate cancer