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The role of HG in the analysis of temporal iteration and interaural correlation
Diffusion Tensor Imaging in Pediatric Brain Tumor Patients
In this dissertation, we outline our efforts to introduce an advanced MRI imaging technique called Diffusion Tensor Imaging (DTI) to the pediatric brain tumor population. We discuss the theory and application of DTI as it was performed in a series of translational investigations at St. Jude Children’s Research Hospital. We present evidence of how the introduction of this technique impacted diagnosis, and treatment. And finally, we demonstrate how DTI was used to investigate cognitive morbidities associated with cancer treatment and how this research provided insight into the underlying pathophysiology involved in the development of these treatment sequela.
This research has generated important insights into the fundamental causes of neuroanatomical and cognitive deficits associated with cancer and cancer therapy. The use of DTI has permitted us to identify potential targets for improved radiological and surgical techniques as well as targets for pharmacological and behavioral interventions that might improve cognitive function in cancer survivors. The discoveries here afford us an opportunity to reduce the negative effects of cancer therapy on patients treated in the future while maintaining successful survival rates
Indirect Structural Connectivity As a Biomarker for Stroke Motor Recovery
In this dissertation project, we demonstrated that diffusion magnetic resonance imaging and measures of indirect structural brain connectivity are sensitive to changes in fiber integrity and connectivity to remote regions in the brain after stroke. Our results revealed new insights into the effects local lesions have on global connectivity—in particular, the cerebellum—and how these changes in connectivity and integrity relate to motor impairment. We tested this methodology on two stroke groups—subacute and chronic—and were able to show that indirect connectivity is sensitive to differences in connectivity during stroke recovery. Our work can inform clinical methods for rehabilitating motor function in stroke individuals. By introducing methodology that extends local damage to remotely connected motor related areas, we can measure Wallerian degeneration in addition to providing the framework to predict improvements in motor impairment score based on structural connectivity at the subacute stage.We used diffusion magnetic resonance imaging (dMRI), probabilistic tractography, and novel graph theory metrics to quantify structural connectivity and integrity after stroke. In the first aim, we improved on a measure of indirect structural connectivity in order to detect remote gray matter regions with reduced connectivity after stroke. In a region-level analysis, we found that indirect connectivity was more sensitive to remote changes in connectivity after stroke than measures of direct connectivity, in particular in cortical, subcortical, and cerebellar gray matter regions that play a central role in sensorimotor function. Adding this information to the integrity of the corticospinal tract (CST) improved our ability to predict motor impairment. In the second aim, we investigated the relationship between white matter integrity, connectivity, and motor impairment by developing a unified measure of white matter structure that extends local changes in white matter integrity along remotely connected fiber tracks. Our measure uniquely identified damaged fiber tracks outside the CST, correlated with motor impairment in the CST better than the FA, and also was able to relate white matter structure in the superior cerebellar peduncle to motor impairment. Our final aim used a novel connectome similarity metric and the measure of indirect structural connectivity in order to identify cross-sectional differences in white matter structure between subacute and chronic stroke. We found more reductions in indirect connectivity in the chronic stroke cerebellar fibers than the subacute group, Additionally, the indirect connectivity of the superior cerebellar peduncle at the subacute stage correlated with the improvement in motor impairment score for the paired participants. In conclusion, indirect connectivity is an important measure of global brain damage and motor impairment after stroke, and can be a useful metric to relate to brain function and stroke recovery
Cerebellar contribution to Cognitive Impairment in early stages of Relapsing-Remitting Multiple Sclerosis: a conventional and rs-fMRI study
Background. The cerebellum is a primary site of Multiple Sclerosis (MS) pathology. Structural and functional MRI studies have demonstrated the role of the
posterior cerebellum in cognitive functions. To date, the “Cerebellar Cognitive Affective Syndrome” (CCAS) scale has never been used to test MS-related Cognitive Impairment (CI) and its association with cerebellar involvement.
Objectives. We investigated the association of MRI structural and functional abnormalities of the cognitive cerebellum with CI and tested the role of the CCAS
scale in detecting CI in a cohort of very early RRMS patients.
Methods. 37 patients with early RRMS and 4 age- and sex-matched healthy controls (HC) were enrolled in this cross-sectional, exploratory study. Cognitive
performances were assessed through BICAMS, D-KEFS ST, and CCAS scale. Using a CCAS scale score cut-off (based on a 50 HC sample), 26/37 (70%) patients were classified as “Normal-CCAS” and 11/37 (30%) as “Impaired-CCAS”. All subjects underwent a conventional and resting-state functional MRI (rs-fMRI) protocol. Comparisons between groups were assessed for structural and functional MRI parameters. Moreover, correlations between cognitive test scores and structural-functional MRI parameters were evaluated.
Results. Patients with pathological score on CCAS also showed CVLT-II and D-KEFS ST low scores. A significant reduction in cerebellar volumetric
parameters was found in the CCAS-impaired MS group compared to the normal one, albeit whole brain WM and thalamic volumes were also significantly reduced. The rs-fMRI analysis revealed higher functional connectivity (FC) between the cognitive cerebellum and most of the functional brain cortical networks in the CCAS-impaired group compared to the normal one.
Conclusions. Our findings suggest that CI in early RRMS is associated with pathological alterations in both structural and functional MRI parameters. Higher
FC between cerebellar-brain networks in CCAS-impaired patients might be the expression of a compensatory hyperactivation of altered cognitive cerebellar
connections. Finally, although the CCAS scale has proven able to detect CI in MS patients, its specificity for cerebellar pathology needs to be further investigated
Pre- and Intraoperative Management of Brainstem Lesions
Brainstem cavernous malformation (BSCM) is a typical brainstem pathology that can lead to significant neurological morbidity. Before making a surgical decision for a patient with BSCM, it is essential to balance the surgery against the natural history of BSCM since individualized risk assessment is crucial for a comprehensive understanding of the natural course of conservatively treated BSCMs (Chapter 2).
In patients with symptomatic and accessible BSCMs, surgery is recommended, however, in some deep-seated locations, surgery is more controversial because of the relatively high morbidity and mortality rates. Therefore, the timing of the surgical option still needs further investigation (Chapter 3). For the surgical treatment in patients with BSCMs, although many safe entry zones (SEZs) into the brainstem have been proposed, it is still debatable on some of them (Chapter 4). Intraoperative direct stimulation is a promising technique in brain surgeries involving eloquent areas. It has been reported to assist in preserving the motor tracts during the resection of (sub)cortical lesions. However, it is sparsely explored for mapping and monitoring the corticospinal tract in brainstem surgery (Chapter 5).
In this thesis, we have investigated safe brainstem surgery from two aspects - preoperative evaluation and intraoperative direct stimulation. The results promote a better understanding of the hemorrhage rate in untreated BSCM before surgical recommendation and help on the timing of surgical decision-making. In addition, this thesis sheds light on the limitation of SEZs in surgical planning for patients with BSCM and the clinical value of direct stimulation for monitoring and mapping of the corticospinal tract during brainstem surgery. These findings contribute to safe surgical planning and lesion resection for brainstem pathologies, especially for the BSCMs
Clinical applications of magnetic resonance imaging based functional and structural connectivity
Advances in computational neuroimaging techniques have expanded the armamentarium of imaging tools available for clinical applications in clinical neuroscience. Non-invasive, in vivo brain MRI structural and functional network mapping has been used to identify therapeutic targets, define eloquent brain regions to preserve, and gain insight into pathological processes and treatments as well as prognostic biomarkers. These tools have the real potential to inform patient-specific treatment strategies. Nevertheless, a realistic appraisal of clinical utility is needed that balances the growing excitement and interest in the field with important limitations associated with these techniques. Quality of the raw data, minutiae of the processing methodology, and the statistical models applied can all impact on the results and their interpretation. A lack of standardization in data acquisition and processing has also resulted in issues with reproducibility. This limitation has had a direct impact on the reliability of these tools and ultimately, confidence in their clinical use. Advances in MRI technology and computational power as well as automation and standardization of processing methods, including machine learning approaches, may help address some of these issues and make these tools more reliable in clinical use. In this review, we will highlight the current clinical uses of MRI connectomics in the diagnosis and treatment of neurological disorders; balancing emerging applications and technologies with limitations of connectivity analytic approaches to present an encompassing and appropriate perspective
Clinical applications of ultra-high field magnetic resonance imaging in multiple sclerosis
Introduction: Magnetic resonance imaging (MRI) is of paramount importance for the early diagnosis of multiple sclerosis (MS) and MRI findings are part of the MS diagnostic criteria. There is a growing interest in the use of ultra-high-field strength 127 Tesla- (7T) MRI to investigate, in vivo, the pathological substrate of the disease. Areas covered: An overview of 7T MRI applications in MS focusing on increased sensitivity for lesion detection, specificity of the central vein sign and better understanding of MS pathophysiology. Implications for disease diagnosis, monitoring and treatment planning are discussed. Expert commentary: 7T MRI provides increased signal-to-noise and contrast-to-noise-ratio that allow higher spatial resolution and better detection of anatomical and pathological features. The high spatial resolution reachable at 7T has been a game changer for neuroimaging applications not only in MS but also in epilepsy, brain tumors, dementia, and neuro-psychiatric disorders. Furthermore, the first 7T device has recently been cleared for clinical use by the food and drug administration
Neuroimaging - Clinical Applications
Modern neuroimaging tools allow unprecedented opportunities for understanding brain neuroanatomy and function in health and disease. Each available technique carries with it a particular balance of strengths and limitations, such that converging evidence based on multiple methods provides the most powerful approach for advancing our knowledge in the fields of clinical and cognitive neuroscience. The scope of this book is not to provide a comprehensive overview of methods and their clinical applications but to provide a "snapshot" of current approaches using well established and newly emerging techniques
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