Resting State FMRI as a Biomarker of Functional Integrity of Spinal Cord

静息态 FMRI 作为脊髓功能完整性的生物标志物

• 批准号: 9423271
• 负责人: John C Gore
• 金额: $ 34.52万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9423271
• 关键词: Adopted; Animals; Back; Biological Markers; Brain; Cervical; Cervical spinal cord structure; Characteristics; Chemicals; Clinical; Clinical Management; Data; Detection; Diffusion Magnetic Resonance Imaging; Disease; Equipment; Frequencies; Functional Magnetic Resonance Imaging; Funding; Grant; Human; Image; Image Analysis; Injury; Intervention; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Monitor; Monkeys; Motivation; Nature; Noise; Pathology; Patients; Pattern; Physical assessment; Physiologic pulse; Physiological; Property; Protocols documentation; Recovery; Recovery of Function; Reporting; Reproducibility; Rest; Role; Seeds; Signal Transduction; Spinal; Spinal Cord; Spinal Cord Diseases; Spinal Injuries; Spinal cord grey matter structure; Structure; Symptoms; System; Therapeutic Intervention; Time; Tissues; Translating; Treatment outcome; Vertebral column; Work; base; blood oxygen level dependent; clinical application; clinical predictors; clinically relevant; functional disability; high risk; human subject; imaging biomarker; indexing; insight; neural circuit; non-invasive imaging; nonhuman primate; novel; novel therapeutics; outcome prediction; patient population; quantitative imaging; relating to nervous system; time use; tool; treatment effect; white matter

Abstract / Summary This proposal aims to extend the work performed under a recent R21 exploratory grant to detect and validate measures of functional connectivity in the human cervical spinal cord (SC) using resting state functional MRI (rsfMRI). The delineation and characterization of neural circuits within the cord may provide a valuable imaging biomarker of functional integrity of the spine applicable to a wide range of disorders. The identification of patterns of highly correlated low frequency blood oxygenation level dependent (BOLD) signals in a resting state has provided a powerful approach to delineate and describe neural circuits in the brain. We recently reported the first reliable detection of similarly correlated low frequency signal fluctuations in SC in a resting state in normal subjects, and showed how functional connectivity may be quantified in the SC both within and between segments. Moreover, in parallel studies in non-human primates we have shown that these spine circuits are selectively and specifically altered by injury and revert back over time in a manner that correlates with functional recovery. We have also shown how multi- parametric MRI can be used to derive quantitative indices of tissue composition and structure which can be related to the functional changes. We hypothesize that the intrinsic neural circuits revealed by rsfMRI in the SC are an important representation of neural synchrony within spinal segments that in turn are an essential feature of normal functions; and that alterations in the patterns of functional connectivity may be used as non-invasive imaging biomarkers of the effects of injury and of therapeutic interventions. We aim (1) to further develop robust, reliable methods to detect and quantify functional connectivity in human SC by optimizing the acquisition and analysis of images at 3T; (2) to implement a novel, multi-parametric spine MRI protocol incorporating diffusion tensor imaging and quantitative magnetization transfer imaging which provide maps of quantitative indices of tissue microstructure and composition; (3) to validate the interpretation of functional connectivity measurements and accompanying changes in white matter composition and microstructure as objective biomarkers of spinal integrity and for guiding clinical management decisions. Imaging data will be correlated with a battery of physical assessments of function in subjects with a wide range of functional impairments to demonstrate their clinical relevance. We will also evaluate their capacity for monitoring and predicting outcome of treatments in patients with cervical spondylotic myelopathy (CSM) and with traumatic spine cord injuries (SCI). The significance of the work is that it will use novel MRI methods that have proven successful in studies of the brain to objectively evaluate functional circuits within the SC, and show that connectivity measures can assess and predict clinically-relevant functions and symptoms. The ability to assess functional integrity has widespread potential for characterizing injuries to the cord, their changes over time, and for assessing novel therapies.

Abstract / Summary This proposal aims to extend the work performed under a recent R21 exploratory grant to detect and validate measures of functional connectivity in the human cervical spinal cord (SC) using resting state functional MRI (rsfMRI). The delineation and characterization of neural circuits within the cord may provide a valuable imaging biomarker of functional integrity of the spine applicable to a wide range of disorders. The identification of patterns of highly correlated low frequency blood oxygenation level dependent (BOLD) signals in a resting state has provided a powerful approach to delineate and describe neural circuits in the brain. We recently reported the first reliable detection of similarly correlated low frequency signal fluctuations in SC in a resting state in normal subjects, and showed how functional connectivity may be quantified in the SC both within and between segments. Moreover, in parallel studies in non-human primates we have shown that these spine circuits are selectively and specifically altered by injury and revert back over time in a manner that correlates with functional recovery. We have also shown how multi- parametric MRI can be used to derive quantitative indices of tissue composition and structure which can be related to the functional changes. We hypothesize that the intrinsic neural circuits revealed by rsfMRI in the SC are an important representation of neural synchrony within spinal segments that in turn are an essential feature of normal functions; and that alterations in the patterns of functional connectivity may be used as non-invasive imaging biomarkers of the effects of injury and of therapeutic interventions. We aim (1) to further develop robust, reliable methods to detect and quantify functional connectivity in human SC by optimizing the acquisition and analysis of images at 3T; (2) to implement a novel, multi-parametric spine MRI protocol incorporating diffusion tensor imaging and quantitative magnetization transfer imaging which provide maps of quantitative indices of tissue microstructure and composition; (3) to validate the interpretation of functional connectivity measurements and accompanying changes in white matter composition and microstructure as objective biomarkers of spinal integrity and for guiding clinical management decisions. Imaging data will be correlated with a battery of physical assessments of function in subjects with a wide range of functional impairments to demonstrate their clinical relevance. We will also evaluate their capacity for monitoring and predicting outcome of treatments in patients with cervical spondylotic myelopathy (CSM) and with traumatic spine cord injuries (SCI). The significance of the work is that it will use novel MRI methods that have proven successful in studies of the brain to objectively evaluate functional circuits within the SC, and show that connectivity measures can assess and predict clinically-relevant functions and symptoms. The ability to assess functional integrity has widespread potential for characterizing injuries to the cord, their changes over time, and for assessing novel therapies.