ECTRIMS eLearning

Volume susceptibility increases as diamagnetic molecules breakdown: implications for myelin digestion during multiple sclerosis (MS) lesion formation
ECTRIMS Learn. Wang Y. 10/27/17; 199929; P1909
Yi Wang
Yi Wang
Contributions
Abstract

Abstract: P1909

Type: Poster

Abstract Category: Late breaking news

Synopsis: Acute MS lesions show increasing magnetic susceptibility, although histology studies show no change in iron content [1]. We show this increase is due to decreased molecular sizes from myelin breakdown using literature research, and quantitative susceptibility mapping (QSM) of myelin degradation in vitro, and acute MS lesions in vivo.
Theory: Diamagnetic susceptibility is proportional to the square of the molecular orbit radius, according to the Langevin theory [2]. For biomolecules, approximated as elongated or globular structures, diamagnetic susceptibility is proportional to the square of the molecular length or the molecular size. Summing over all molecules in a unit volume, the magnitude of the volume diamagnetic susceptibility increases linearly with the size of diamagnetic molecules when the concentration of diamagnetic material remains the same.
Methods: Volume susceptibility values of selected biomolecules, determined from a literature search, were linearly regressed against molecular weights. Purified myelin was incubated with 13% SDS for 16 hours at 37°C. Tubes of 13% SDS, purified myelin, and myelin incubated with 13% SDS were imaged using a gradient echo (GRE) MRI sequence for QSM. QSM imaging was also performed on three relapsing-remitting MS patients with Gadolinium (Gd) enhancing lesions. Region of interest (ROI) analysis was performed to determine susceptibility changes for all scans.
Results: Regression analysis demonstrated excellent linear relationship between susceptibility and molecular weight for the biomolecules. ROI analysis showed an increase in volume susceptibility of purified myelin from -42.3 parts per billion (ppb) to -15.3 ppb from breakdown with SDS. Increases in lesion susceptibility values in MS patients were 18.4, 5.7 and 2.1 ppb.
Discussion: Literature and in vitro studies demonstrate volumetric susceptibility increases as constituent diamagnetic molecular size decreases. In vivo QSM data showed susceptibility increase during acute MS lesion formation at the time when the blood brain barrier (BBB) is closed, consistent with reported MRI phase change during this period.
Conclusion: Volume susceptibility measured on QSM increases as diamagnetic molecular sizes decreases, and myelin breakdown by macrophage digestion may contribute to the rapid susceptibility increase in acute MS lesions.
References:
[1]. Mehta V., PLoS One 2013.
[2] Wang, Y. ISBN-978-1479350414
[3]. Liu, Z., et al. MRM. 2017. 78(1):303-315
Disclosure:
Yi Wang: Nothing to disclose
Kofi Deh: Nothing to disclose
Thanh D. Nguyen: Nothing to disclose
Kelly M. Gillen: Nothing to disclose
Shun Zhang: Nothing to disclose
Ajay Gupta: Nothing to disclose
Susan Gauthier: Nothing to disclose
David Pitt: Nothing to disclose

Abstract: P1909

Type: Poster

Abstract Category: Late breaking news

Synopsis: Acute MS lesions show increasing magnetic susceptibility, although histology studies show no change in iron content [1]. We show this increase is due to decreased molecular sizes from myelin breakdown using literature research, and quantitative susceptibility mapping (QSM) of myelin degradation in vitro, and acute MS lesions in vivo.
Theory: Diamagnetic susceptibility is proportional to the square of the molecular orbit radius, according to the Langevin theory [2]. For biomolecules, approximated as elongated or globular structures, diamagnetic susceptibility is proportional to the square of the molecular length or the molecular size. Summing over all molecules in a unit volume, the magnitude of the volume diamagnetic susceptibility increases linearly with the size of diamagnetic molecules when the concentration of diamagnetic material remains the same.
Methods: Volume susceptibility values of selected biomolecules, determined from a literature search, were linearly regressed against molecular weights. Purified myelin was incubated with 13% SDS for 16 hours at 37°C. Tubes of 13% SDS, purified myelin, and myelin incubated with 13% SDS were imaged using a gradient echo (GRE) MRI sequence for QSM. QSM imaging was also performed on three relapsing-remitting MS patients with Gadolinium (Gd) enhancing lesions. Region of interest (ROI) analysis was performed to determine susceptibility changes for all scans.
Results: Regression analysis demonstrated excellent linear relationship between susceptibility and molecular weight for the biomolecules. ROI analysis showed an increase in volume susceptibility of purified myelin from -42.3 parts per billion (ppb) to -15.3 ppb from breakdown with SDS. Increases in lesion susceptibility values in MS patients were 18.4, 5.7 and 2.1 ppb.
Discussion: Literature and in vitro studies demonstrate volumetric susceptibility increases as constituent diamagnetic molecular size decreases. In vivo QSM data showed susceptibility increase during acute MS lesion formation at the time when the blood brain barrier (BBB) is closed, consistent with reported MRI phase change during this period.
Conclusion: Volume susceptibility measured on QSM increases as diamagnetic molecular sizes decreases, and myelin breakdown by macrophage digestion may contribute to the rapid susceptibility increase in acute MS lesions.
References:
[1]. Mehta V., PLoS One 2013.
[2] Wang, Y. ISBN-978-1479350414
[3]. Liu, Z., et al. MRM. 2017. 78(1):303-315
Disclosure:
Yi Wang: Nothing to disclose
Kofi Deh: Nothing to disclose
Thanh D. Nguyen: Nothing to disclose
Kelly M. Gillen: Nothing to disclose
Shun Zhang: Nothing to disclose
Ajay Gupta: Nothing to disclose
Susan Gauthier: Nothing to disclose
David Pitt: Nothing to disclose

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies