Creation of new tissue priors for automated delineation of basal ganglia in magnetic resonance imaging

The advent of magnetic resonance (MR) imaging has brought to the field of neurosciences the stupendous ability of in-vivo study of the human brain's tissular properties. More recent developments in the field of computational anatomy have led to automated approaches of volumetric assessment of the brain in voxel-based morphometry (VBM). VBM has provided significant understanding about physiopathology of brain diseases, including psychiatric and neurodegenerative diseases (NDDs). VBM performs tissue classification using algorithms that rely on contrast between tissues and probabilistic maps, termed tissue priors. These algorithms have provided accurate and satisfying study of the human cortex. However, tissue classification of deep gray matter such as the basal ganglia has been found to be largely unreliable. Conventional T1-weighted MR imaging provides lower contrast for deep gray matter than the cortical gray matter. The main reason for this contrast bias is the higher iron concentration in those structures. Moreover, iron deposits increase in the normal ageing adult and reach pathological concentrations in a wide number of neurological disorders including NDDs. Accurate assessment is thus challenged for subcortical structures in both health and disease. Recently, quantitative MR imaging (qMRI) has been developed to allow quantitative assessment of tissular microstructure of the brain. Those new sequences, such as magnetization transfer saturation (MT) and effective transverse relaxation rate (R2*) parameter maps, provide better contrast by displaying quantitative surrogates for myelin and iron respectively. MT parameter maps have shown to overcome high iron content sensitivity and to be highly suitable for automated delineation of the basal ganglia. Although MT parameter maps provide sufficient contrast, current tissue priors remain insufficient to provide satisfying tissue classification. In this work, we created robust and accurate tissue priors for deep gray matter

Neuroimaging in Friedreich's ataxia : new approaches and clinical aplication

Orientadores: Marcondes Cavalcante França Junior, Andreia Vasconcellos FariaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A ataxia de Friedreich (FRDA) é a ataxia autossômica recessiva mais comum no mundo. Clinicamente, é caracterizada por início precoce, alterações sensoriais e ataxia de lenta progressão. Os estudos de imagem têm focado somente em estruturas infratentoriais, desconsiderando o envolvimento de estruturas supratentoriais, diferenças fenotípicas e duração da doença, bem como a evolução do dano neurológico. Portanto, o objetivo deste trabalho é avaliar, por meio de imagens de ressonância magnética multimodal, pacientes com ataxia de Friedreich a fim de compreender a evolução do dano encefálico, identificar o padrão de dano encefálico entre os fenótipos da doença, os sítios de depósitos de ferro extra-cerebelares e as primeiras estruturas acometidas na doença. A fim de atingir todos os objetivos, foram recrutados 25 pacientes adultos com a forma clássica da doença, 13 pacientes com início tardio e 12 pacientes pediátricos. Para quantificar a gravidade da doença foi utilizada a escala FARS. O dano estrutural de substância cinza e branca foi avaliado via imagens de ressonância magnética ponderadas em T1, T2 e DTI. Para análise de tais imagens foram utilizadas as ferramentas FreeSurfer, T1 MultiAtlas, DTI Multiatlas, SPM, SpineSeg e TBSS. As comparações de grupos revelaram comprometimento microestrutural multifocal na substância branca encefálica na FRDA, com dano extenso nos pedúnculos cerebelares, corpo caloso e tratos piramidais. Encontramos também alterações na substância cinzenta no núcleo denteado do cerebelo, tronco e córtex motor. Nós não identificamos mudanças volumétricas longitudinais, porém análises prospectivas da substância branca identificaram anormalidades microestruturais progressivas no corpo caloso, tratos piramidais e pedúnculos cerebelares superiores após um ano de seguimento. A respeito do estudo comparando o tipo clássico e o tipo tardio (cFRDA vs. LOFA), nós mostramos que ambos os fenótipos possuem um padrão de anormalidades similares, mas não idênticas. Embora sutis, as diferenças estruturais encontradas ajudam a explicar a variabilidade fenotípica entre estas duas apresentações da doença. Por exemplo, o maior dano microestrutural no trato córtico-espinhal no grupo LOFA ajuda a explicar os sinais piramidais mais exuberantes neste grupo. Não fomos capazes de identificar depósitos de ferro cerebrais nos pacientes com FRDA. Neste sentido, tais depósitos ficariam restritos somente ao núcleo denteado do cerebelo. Por fim, fomos capazes de observar que a manifestação inicial da doença, vista em pacientes pediátricos, se concentra na medula espinhal e no pedúnculo cerebelar inferiorAbstract: Friedreich¿s ataxia (FRDA) is the most common autosomal-recessive ataxia worldwide; it is characterized by early onset, sensory abnormalities and slowly progressive ataxia. Besides that, most of neuroimaging studies have been focused only in infratentorial structures of adult patients. Furthermore, studies comparing different phenotypes of disease does not exist. Therefore, the objective of this study is to assess, using multimodal magnetic (MRI) resonance imaging, patients with Friedreich ataxia to better comprehend the progression of brain damage, to identify the pattern of damage across disease phenotypes, to identify areas with abnormal iron deposits in the brain and to characterize the structures initially damaged in early disease stages. To accomplish that, we enrolled 25 adult patients with classical FRDA, 13 patients with late-onset FRDA and 12 pediatric patients. The FARS scale was employed to quantify the disease severity. To assess the structural damage in gray and white matter, we acquired T1-weighted, T2-weighted and DTI images of the brain. To evaluate these images, we used the following tools: FreeSurfer, T1 MultiAtlas, SPM, DTI MultiAtlas, SpineSeg and TBSS. After group comparisons, there was widespread microstructural damage in the cerebral white matter, including cerebellar peduncles, corpus callosum and pyramidal tracts of patients with FRDA. We also found gray matter volumetric reduction in the dentate nuclei of the cerebellum, brainstem and motor cortex. We did not find volumetric reduction over time, but there was progressive white matter microstructural damage in the corpus callosum, pyramidal tracts and superior cerebellar peduncles after 1 year of follow-up. Regarding the disease phenotypes, we found that both classical FRDA and LOFA have similar, but not identical neuroimaging signatures. Although subtle, the structural differences might help to explain the phenotypic differences seen in both conditions. The corticospinal tracts are damaged in both conditions, but more severely in the late-onset FRDA group, which may explain why pyramidal signs are more evident in the latter subgroup. We failed to identify iron deposits in brain regions other than the dentate nuclei of patients with FRDA. Finally, we found that the spinal cord and inferior cerebellar peduncles are the structures compromised in pediatric patients with FRDADoutoradoFisiopatologia MédicaDoutor em Ciências2014/19786-7, 2015/09793-9FAPES

Recommended Implementation of Quantitative Susceptibility Mapping for Clinical Research in The Brain: A Consensus of the ISMRM Electro-Magnetic Tissue Properties Study Group

This article provides recommendations for implementing quantitative susceptibility mapping (QSM) for clinical brain research. It is a consensus of the ISMRM Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available give rise to the need in the neuroimaging community for guidelines on implementation. This article describes relevant considerations and provides specific implementation recommendations for all steps in QSM data acquisition, processing, analysis, and presentation in scientific publications. We recommend that data be acquired using a monopolar 3D multi-echo GRE sequence, that phase images be saved and exported in DICOM format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields should be removed within the brain mask using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of whole brain as a region of interest in the analysis, and QSM results should be reported with - as a minimum - the acquisition and processing specifications listed in the last section of the article. These recommendations should facilitate clinical QSM research and lead to increased harmonization in data acquisition, analysis, and reporting

Quantitative MRI correlates of hippocampal and neocortical pathology in intractable temporal lobe epilepsy

Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI image registration, which finds dense spatial correspondence between both modalities. This protocol was divided in two steps whereby sparsely sectioned histology from temporal lobe specimens was first registered to the intermediate ex-vivo MRI which is then registered to the in-vivo MRI, completing a pipeline for histology to in-vivo MRI registration. When correlating relaxometry and DTI with neuronal density and morphology in the temporal lobe neocortex, I found T1 to be a predictor of neuronal density in the neocortical GM and demonstrated that employing multi-parametric MRI (combining T1 and FA together) provided a significantly better fit than each parameter alone in predicting density of neurons. This work was the first to relate in-vivo T1 and FA values to the proportion of neurons in GM. When investigating these quantitative multimodal parameters with histological features within the hippocampal subfields, I demonstrated that MD correlates with neuronal density and size, and can act as a marker for neuron integrity within the hippocampus. More importantly, this work was the first to highlight the potential of subfield relaxometry and diffusion parameters (mainly T2 and MD) as well as volumetry in predicting the extent of cell loss per subfield pre-operatively, with a precision so far unachievable. These results suggest that high-resolution quantitative MRI sequences could impact clinical practice for pre-operative evaluation and prediction of surgical outcomes of intractable epilepsy

Improved test-retest reliability of R2∗\textit{R}_2^* and susceptibility quantification using multi-shot multi echo 3D EPI

This study aimed to evaluate the potential of 3D echo-planar imaging (EPI) for improving the reliability of $T_2^*$-weighted ($T_2^*w$) data and quantification of $\textit{R}_2^*$ decay rate and susceptibility ($\chi$) compared to conventional gradient echo (GRE)-based acquisition. Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of $\textit{R}_2^*$ and $\chi$ were quantified and compared using their inter-scan difference to evaluate the test-retest reliability. Inter-protocol differences of $\textit{R}_2^*$ and $\chi$ between GRE and EPI were also measured voxel by voxel and in selected ROIs to test the consistency between the two acquisition methods. The quantifications of $\textit{R}_2^*$ and $\chi$ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. This result suggested multi-shot multi-echo 3D EPI can be a useful alternative acquisition method for $T_2^*w$ MRI and quantification of $\textit{R}_2^*$ and $\chi$ with reduced scan time, improved test-retest reliability and similar accuracy compared to commonly used 3D GRE.Comment: 18 pages, 8 figures and 1 tabl

Neuroimaging at 7 Tesla: a pictorial narrative review

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders

Development and evaluation of a novel framework for subcortical gray matter segmentation using quantitative magnetic susceptibility and R2* mapping

Quantitative susceptibility mapping (QSM) and effective relaxation rate (R∗2) mapping are promising magnetic resonance imaging (MRI) techniques to study iron content in the human brain in vivo. The ability to quantify iron content in subcortical gray matter (SGM) is important to better understand its role in neurodegenerative diseases as well as during normal brain aging. However, accurate determination of tissue magnetic susceptibility and R∗2 in brain structures, such as SGM, may be challenging due to potential segmentation inaccuracies, specifically when performed automatically. The present thesis introduces a robust framework to automatically segment and characterize SGM using quantitative susceptibility maps and exemplarily applies it to investigate iron-related susceptibility and R∗2 changes in patients with multiple sclerosis (MS) in comparison to controls

Applications of MRI Magnetic Susceptibility Mapping in PET-MRI Brain Studies

Magnetic susceptibility mapping (SM) uses magnetic resonance imaging (MRI) phase images to produce maps of the magnetic susceptibility (χ) of tissues. This work focuses on the applications of SM-based imaging to PET-MRI, the hybrid imaging modality which combines positron emission tomography (PET) with MRI. First, the potential of using SM to aid PET attenuation correction (AC) is explored. AC for PET-MRI is challenging as PET-MRI provides no information regarding the electron density of tissues. Recently proposed SM methods for calculating the χ in regions of no MRI signal are used to segment air, bone and soft tissue in order to create AC maps. In the head, SM methods are found to produce inferior air/bone segmentations to high-performing AC methods, but result in more accurate AC than ultrashort-echo (UTE)-based air/bone segmentations, and may be able to provide additional information in subjects with atypical anatomy. Secondly, a SM pipeline for inclusion in a PET-MRI study into biomarkers for Alzheimer’s disease (AD) is developed. In the Insight46 study 500 healthy subjects from the 1946 MRC National Survey of Health and Development are undergoing a comprehensive PET-MRI protocol at two time-points. SM processing methods are compared and optimised, and a method for processing images with oblique imaging planes is developed. The effect of using different tools for automated segmentation of regions of interest (ROIs) on reported regional χ values is analysed. The ROIs resulting from different tools are found to result in large differences in χ values. FIRST is chosen as the most appropriate ROI segmentation tool for this study based on anatomical accuracy as assessed by a neuroradiologist. Initial analysis of χ values from 100 subjects using data from the first time-point is carried out. No significant association with regional χ values is found for amyloid status, PET radiotracer uptake, or APOE genotype