Contributions
Abstract: P556
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Lack of an in vivo surrogate marker of axonal integrity represents a critical barrier to the development of neuroprotective drugs for patients with multiple sclerosis (MS). We successfully implemented 2 imaging methods namely selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment spherical microscopic diffusion imaging using spherical mean techniques (SMT). We previously proved that the SIR-qMT derived macromolecular to free pool size ratio (PSR) and the SMT derived axonal volume fraction (Vax) are indirect but histologically specific metrics of myelin and axonal integrity. We here hypothesize that PSR and Vax are sensitive to pathological changes in vivo as they allow quantifiable indices reflective of myelin and axonal content, hence showing hallmarks of neurodegenerative tissue injury in MS brains. Ten patients with MS and 4 healthy controls were imaged on a 3.0 Tesla whole body scanner equipped with a 32-channel receiver head coil. Clinical 2-mm thick sequences, SIR-qMT and SMT were obtained. Anatomically matched regions of interest in normal appearing white matter (NAWM), T2-hyperitense and T1-hypointense lesions in patients and normal white matter (NWM) in healthy controls were contoured; PSR and Vax values of these regions were derived. PSR and Vax differed (p≤0.0001, paired t-test) between lesions with different appearance on conventional scans, between each lesion type and NAWM but not (unpaired t-test) between NAWM and NWM. Vax ranged from 22% to 60% in T1-hypointense lesions and was reduced by 36% and 100%, in T2-hyperitense and T1-hypointense lesions, respectively, compared to NAWM. In lesions, axonal content was associated to that of myelin (r=0.714, p≤0.0001, Pearson correlation analyses). We provide for the first time an indirect quantitative estimate of the amount of residual axons in vivo demonstrating that nearly 75% of axons are lost in T1-hypointense lesions. Combining SIR-qMT and SMT improves our ability to discern axonal and myelin pathology and delivers biomarkers of neurodegeneration and repair in MS.
Disclosure: Nothing to disclose
Abstract: P556
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Lack of an in vivo surrogate marker of axonal integrity represents a critical barrier to the development of neuroprotective drugs for patients with multiple sclerosis (MS). We successfully implemented 2 imaging methods namely selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment spherical microscopic diffusion imaging using spherical mean techniques (SMT). We previously proved that the SIR-qMT derived macromolecular to free pool size ratio (PSR) and the SMT derived axonal volume fraction (Vax) are indirect but histologically specific metrics of myelin and axonal integrity. We here hypothesize that PSR and Vax are sensitive to pathological changes in vivo as they allow quantifiable indices reflective of myelin and axonal content, hence showing hallmarks of neurodegenerative tissue injury in MS brains. Ten patients with MS and 4 healthy controls were imaged on a 3.0 Tesla whole body scanner equipped with a 32-channel receiver head coil. Clinical 2-mm thick sequences, SIR-qMT and SMT were obtained. Anatomically matched regions of interest in normal appearing white matter (NAWM), T2-hyperitense and T1-hypointense lesions in patients and normal white matter (NWM) in healthy controls were contoured; PSR and Vax values of these regions were derived. PSR and Vax differed (p≤0.0001, paired t-test) between lesions with different appearance on conventional scans, between each lesion type and NAWM but not (unpaired t-test) between NAWM and NWM. Vax ranged from 22% to 60% in T1-hypointense lesions and was reduced by 36% and 100%, in T2-hyperitense and T1-hypointense lesions, respectively, compared to NAWM. In lesions, axonal content was associated to that of myelin (r=0.714, p≤0.0001, Pearson correlation analyses). We provide for the first time an indirect quantitative estimate of the amount of residual axons in vivo demonstrating that nearly 75% of axons are lost in T1-hypointense lesions. Combining SIR-qMT and SMT improves our ability to discern axonal and myelin pathology and delivers biomarkers of neurodegeneration and repair in MS.
Disclosure: Nothing to disclose