Assessing early white matter predictors of syntactic abilities in post-stroke aphasia using HARDI-based tractography

La recherche de prédicteurs d’habilités langagières en aphasie post-accident vasculaire cérébral (AVC) basés sur la matière blanche a récemment vu un élan. Cela a été motivé par l’émergence du modèle à double-voie où des faisceaux de matière blanche dorsaux et ventraux jouent un rôle important dans le langage, ainsi que par l’avènement de la tractographie basée sur l’imagerie par résonance magnétique (IRM) de diffusion permettant l’étude in-vivo des faisceaux de matière blanche et de leurs propriétés structurelles. Les caractéristiques structurelles et la charge lésionnelle des faisceaux de matière blanche ont permis de prédire les troubles langagiers dans la phase chronique dans quelques études. Cependant, les prédicteurs aigus de matière blanche des habilités syntaxiques en aphasie post-AVC chronique sont méconnus. L’exploitation de la tractographie dans l’étude des faisceaux langagiers de matière blanche a été limitée par plusieurs défis méthodologiques, dont la difficulté de reconstruire des faisceaux ayant une architecture complexe. Des progrès méthodologiques ont été récemment introduits afin d’adresser ces limites, dont le plus important est la tractographie basée sur l’imagerie à haute résolution angulaire (« HARDI »). Cependant, la fiabilité test-retest de la reconstruction et des propriétés structurelles d’une approche de tractographie HARDI de pointe n’a pas encore été évaluée. Le premier article de cette thèse visait à évaluer la fiabilité test-retest de la reconstruction et des propriétés structurelles (anisotropie fractionnelle, FA; diffusivité moyenne, axiale et radiale, MD, AD, RD; nombre d’orientations de fibres, NuFO; volume du faisceau; longueur moyenne des « streamlines ») de faisceaux langagiers majeurs (arqué, inférieur fronto-occipital, inférieur longitudinal, unciné, AF, IFOF, ILF, UF) obtenus avec une approche de tractographie HARDI de pointe. La majorité des mesures de propriétés structurelles ont montré une bonne ou excellente fiabilité. Ces résultats ont des implications importantes pour l’utilisation d’une telle approche pour l’étude des faisceaux langagiers de matière blanche, car ils renforcent la confiance dans la stabilité des reconstructions et les propriétés structurelles obtenus avec la tractographie HARDI. Le second article de cette thèse visait à déterminer si et quelles propriétés structurelles (FA, AD, volume du faisceau), et la charge lésionnelle, de l’AF et l’UF gauches dans la phase aigüe (≤ 3 jours), obtenus avec l’approche de tractographie HARDI utilisée dans le premier article, prédisent les habilités syntaxiques dans le discours spontané en aphasie post-AVC chronique (≥ 6 mois). Des régressions multiples ascendantes ont révélé que le volume de l’AF prédit la production des verbes, la complexité des phrases et la complexité de la structure argumentale du verbe. Le volume de l’UF a amélioré la prédiction de cette dernière. Ces résultats indiquent que le volume semble être un bon prédicteur précoce des habilités syntaxiques dans le discours spontané en aphasie post-AVC chronique. Mis ensemble, les résultats de cette thèse soulignent l’utilité d’une approche de tractographie HARDI de pointe et son potentiel pour le développement futur de biomarqueurs précoces pouvant améliorer le pronostic de patients ayant une aphasie post-AVC chronique. Cela pourrait promouvoir l’optimisation des soins et le développement de thérapies pour le bienfait des patients et leurs familles.The search for white matter predictors of language abilities in post-stroke aphasia has gained momentum in recent years. This growing interest has been driven by the emergence of the dual-stream framework where dorsal and ventral white matter bundles play an important functional role in language, as well as the advent of diffusion magnetic resonance imaging (MRI)-based tractography which allows the in-vivo investigation of white matter bundles and their structural properties. Structural characteristics, as well as the lesion load, of white matter bundles have been previously found to predict language impairments in the chronic phase. However, little is known about acute white matter predictors of syntactic abilities in chronic post-stroke aphasia. Leveraging tractography to study white matter language bundles has been limited by several methodological challenges, such as the difficulty of reconstructing white matter bundles with a complex fiber architecture. A number of methodological advances have been introduced fairly recently to address these limitations, the most important of which is the advent of tractography based on High Angular Resolution Imaging (HARDI). However, the test-retest reliability of the reconstruction and structural properties of a state-of-the-art HARDI-based tractography pipeline has not been previously assessed. The first article of the present thesis aimed to assess the test-retest reliability of the reconstruction and structural properties (fractional anisotropy, FA; mean, axial, radial diffusivity, MD, AD, RD; number of fiber orientations, NuFO; bundle volume; mean length of streamlines) of major white matter language bundles (arcuate, inferior fronto-occipital, inferior longitudinal, and uncinate fasciculi, AF, IFOF, ILF, UF) obtained using a state-of-the-art HARDI-based tractography pipeline. Most measures of structural properties showed good to excellent test-retest reliability. These findings have important implications for the use of such a pipeline for the study of white matter language bundles, as they increase our confidence that the reconstructions and structural properties obtained from the tractography pipeline are stable and not due to random variations in measurement. The second article of the thesis aimed to determine whether and which structural properties (FA, AD, bundle volume), as well as the lesion load, of the left AF and UF in the acute phase post-stroke (≤ 3 days), obtained with the same state-of-the-art HARDI-based tractography pipeline used in the first article, predict syntactic abilities in connected speech in chronic post-stroke aphasia (≥ 6 months). Forward multiple regressions revealed that the left AF’s volume predicted the percentage of verbs produced, the structural complexity of sentences, as well as verb-argument structure complexity. The left UF’s volume improved the prediction of verbs with a complex argument structure. These findings indicate that the bundle volume may be a good early predictor of syntactic ability in connected speech in chronic post-stroke aphasia. Overall, the findings of this thesis highlight the usefulness of a state-of-the-art HARDI-based tractography approach and its potential for the future development of early biomarkers that could improve the prognosis and personalized care of patients with chronic post-stroke aphasia. This would promote the optimization of patient care and the development of therapies for the benefit of patients and their families

Test-retest reliability of diffusion measures extracted along white matter language fiber bundles using HARDI-based tractography

High angular resolution diffusion imaging (HARDI)-based tractography has been increasingly used in longitudinal studies on white matter macro- and micro-structural changes in the language network during language acquisition and in language impairments. However, test-retest reliability measurements are essential to ascertain that the longitudinal variations observed are not related to data processing. The aims of this study were to determine the reproducibility of the reconstruction of major white matter fiber bundles of the language network using anatomically constrained probabilistic tractography with constrained spherical deconvolution based on HARDI data, as well as to assess the test-retest reliability of diffusion measures extracted along them. Eighteen right-handed participants were scanned twice, one week apart. The arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi were reconstructed in the left and right hemispheres and the following diffusion measures were extracted along each tract: fractional anisotropy, mean, axial, and radial diffusivity, number of fiber orientations, mean length of streamlines, and volume. All fiber bundles showed good morphological overlap between the two scanning timepoints and the test-retest reliability of all diffusion measures in most fiber bundles was good to excellent. We thus propose a fairly simple, but robust, HARDI-based tractography pipeline reliable for the longitudinal study of white matter language fiber bundles, which increases its potential applicability to research on the neurobiological mechanisms supporting language

The LONI QC System: A Semi-Automated, Web-Based and Freely-Available Environment for the Comprehensive Quality Control of Neuroimaging Data.

Quantifying, controlling, and monitoring image quality is an essential prerequisite for ensuring the validity and reproducibility of many types of neuroimaging data analyses. Implementation of quality control (QC) procedures is the key to ensuring that neuroimaging data are of high-quality and their validity in the subsequent analyses. We introduce the QC system of the Laboratory of Neuro Imaging (LONI): a web-based system featuring a workflow for the assessment of various modality and contrast brain imaging data. The design allows users to anonymously upload imaging data to the LONI-QC system. It then computes an exhaustive set of QC metrics which aids users to perform a standardized QC by generating a range of scalar and vector statistics. These procedures are performed in parallel using a large compute cluster. Finally, the system offers an automated QC procedure for structural MRI, which can flag each QC metric as being 'good' or 'bad.' Validation using various sets of data acquired from a single scanner and from multiple sites demonstrated the reproducibility of our QC metrics, and the sensitivity and specificity of the proposed Auto QC to 'bad' quality images in comparison to visual inspection. To the best of our knowledge, LONI-QC is the first online QC system that uniquely supports the variety of functionality where we compute numerous QC metrics and perform visual/automated image QC of multi-contrast and multi-modal brain imaging data. The LONI-QC system has been used to assess the quality of large neuroimaging datasets acquired as part of various multi-site studies such as the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study and the Alzheimer's Disease Neuroimaging Initiative (ADNI). LONI-QC's functionality is freely available to users worldwide and its adoption by imaging researchers is likely to contribute substantially to upholding high standards of brain image data quality and to implementing these standards across the neuroimaging community

Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients

Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia

White matter changes and confrontation naming in retired aging national football league athletes

Using diffusion tensor imaging (DTI), we assessed the relationship of white matter integrity and performance on the Boston Naming Test (BNT) in a group of retired professional football players and a control group. We examined correlations between fractional anisotropy (FA) and mean diffusivity (MD) with BNT T-scores in an unbiased voxelwise analysis processed with tract-based spatial statistics (TBSS). We also analyzed the DTI data by grouping voxels together as white matter tracts and testing each tract's association with BNT T-scores. Significant voxelwise correlations between FA and BNT performance were only seen in the retired football players (p < 0.02). Two tracts had mean FA values that significantly correlated with BNT performance: forceps minor and forceps major. White matter integrity is important for distributed cognitive processes, and disruption correlates with diminished performance in athletes exposed to concussive and subconcussive brain injuries, but not in controls without such exposure

A test-retest reliability analysis of diffusion measures of white matter tracts relevant for cognitive control

Recent efforts to replicate structural brain-behavior correlations have called into question the replicability of structural brain measures used in cognitive neuroscience. Here, we report an evaluation of test-retest reliability of diffusion tensor imaging (DTI) measures, including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, in several white matter tracts previously shown to be involved in cognitive control. In a data set consisting of 34 healthy participants scanned twice on a single day, we observe overall stability of DTI measures. This stability remained in a subset of participants who were also scanned a third time on the same day as well as in a 2-week follow-up session. We conclude that DTI measures in these tracts show relative stability, and that alternative explanations for the recent failures of replication must be considered

Detection of Pathologic Changes Following Traumatic Brain Injury Using Magnetic Resonance Imaging

Background: Approximately two percent of Finns have sequels after traumatic brain injury (TBI), and many TBI patients are young or middle-aged. The high rate of unemployment after TBI has major economic consequences for society, and traumatic brain injury often has remarkable personal consequences, as well. Structural imaging is often needed to support the clinical TBI diagnosis. Accurate early diagnosis is essential for successful rehabilition and, thus, may also influence the patient’s outcome. Traumatic axonal injury and cortical contusions constitute the majority of traumatic brain lesions. Several studies have shown magnetic resonance imaging (MRI) to be superior to computed tomography (CT) in the detection of these lesions. However, traumatic brain injury often leads to persistent symptoms even in cases with few or no findings in conventional MRI. Aims and methods: The aim of this prospective study was to clarify the role of conventional MRI in the imaging of traumatic brain injury, and to investigate how to improve the radiologic diagnostics of TBI by using more modern diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) techniques. We estimated, in a longitudinal study, the visibility of the contusions and other intraparenchymal lesions in conventional MRI at one week and one year after TBI. We used DWI-based measurements to look for changes in the diffusivity of the normal-appearing brain in a case-control study. DTI-based tractography was used in a case-control study to evaluate changes in the volume, diffusivity, and anisotropy of the long association tracts in symptomatic TBI patients with no visible signs of intracranial or intraparenchymal abnormalities on routine MRI. We further studied the reproducibility of different tools to identify and measure white-matter tracts by using a DTI sequence suitable for clinical protocols. Results: Both the number and extent of visible traumatic lesions on conventional MRI diminished significantly with time. Slightly increased diffusion in the normal-appearing brain was a common finding at one week after TBI, but it was not significantly associated with the injury severity. Fractional anisotropy values, that represent the integrity of the white-matter tracts, were significantly diminished in several tracts in TBI patients compared to the control subjects. Compared to the cross-sectional ROI method, the tract-based analyses had better reproducibility to identify and measure white-matter tracts of interest by means of DTI tractography. Conclusions: As conventional MRI is still applied in clinical practice, it should be carried out soon after the injury, at least in symptomatic patients with negative CT scan. DWI-related brain diffusivity measurements may be used to improve the documenting of TBI. DTI tractography can be used to improve radiologic diagnostics in a symptomatic TBI sub-population with no findings on conventional MRI. Reproducibility of different tools to quantify fibre tracts vary considerably, which should be taken into consideration in the clinical DTI applications.Siirretty Doriast

Diffusion-tensor MRI methods to study and evaluate muscle architecture

The thesis describes the development of various approaches for measuring muscle architectural parameters using Diffusion Tensor MR Imaging (DTI). It also illustrates how to apply them to study changes in muscle architecture after an injury prevention program.In Chapter 2, because manual segmentation of muscles is cumbersome, we validated a semi-automatic framework for estimating DTI indices in upper leg muscles. This method reduced segmentation time by a factor of three in a cross-sectional study design and can be used fully automatically in a longitudinal assessment of changes in DTI indices.Chapter 3 was a feasibility study measuring fiber orientation changes with DTI in calf muscles and sub-compartments of the Soleus and Tibialis Anterior during plantarflexion and dorsiflexion. Differences in fiber orientations corresponded to the known agonist-antagonist function of the muscles. This shows that DTI can be utilized to assess changes in muscle orientation due to posture or training.In Chapter 4, we compared DTI fiber tractography for Vastus Lateralis fiber architecture assessment with 3D ultrasonography (3D-US). We discovered that both methods have their advantages and disadvantages, with the agreement between the two techniques being moderate.Finally, in Chapter 5, we examined the effects of a hamstring injury prevention exercise on the muscle architectural parameters of basketball players. DTI was employed to quantify changes in fiber orientation and length using tractography and fiber orientation maps. It was observed that the Semitendinosus fascicle length increased after the Nordics exercise, while the Biceps Femoris long head fiber orientation decreased following the Divers intervention