Keep an open mind: myelin estimates reflect multiple elements of tissue composition

Poster No:

1971 

Submission Type:

Abstract Submission 

Authors:

Alma Davidson1, Roman Fleysher2, Jing Zhang3, Michael Lipton1,2

Institutions:

1Department of Biomedical Engineering, Columbia University, New York, NY, 2Department of Radiology, Columbia University Irving Medical Center, New York, NY, 3GE HealthCare, Mississauga, Ontario

First Author:

Alma Davidson  
Department of Biomedical Engineering, Columbia University
New York, NY

Co-Author(s):

Roman Fleysher, PhD  
Department of Radiology, Columbia University Irving Medical Center
New York, NY
Jing Zhang  
GE HealthCare
Mississauga, Ontario
Michael Lipton  
Department of Biomedical Engineering, Columbia University|Department of Radiology, Columbia University Irving Medical Center
New York, NY|New York, NY

Introduction:

Myelin water imaging (MWI) is an MRI approach to estimate myelin content, based on water trapped between myelin layers. Restricted mobility water between tightly wrapped lipid bilayers confers a T2 relaxation time shorter than that of intra- and extracellular water, allowing differentiation between compartments based on T2 (van der Weijden et al., 2023). However, apparent T2 can be shortened due to mesoscopic magnetic field inhomogeneities such as those created by iron leading to biased estimation of myelin water fraction (MWF) (Birkl et al., 2019). In this study we show that conventionally estimated MWF in globus pallidus is likely biased by the presence of iron, a phenomenon which may impact other brain regions and vary in disease states.

Methods:

The study was approved by the local institutional review board and participants gave written consent. MRI was collected in 96 healthy individuals (ages 19-31, 43 females), using a 3T GE Signa Premier MRI scanner and 48-channel head coil. MWF maps were produced by decomposing signal decay from a 32-echo spin-echo (GRASE) acquisition (TR=1000ms, TE=ΔTE=9.6ms, FOV=256mmx256mm, 2mm isotropic resolution, EPI length=5) using DECAES, and taking the short (T2<40ms) component as myelin (Doucette et al., 2020). Maps of T2* were produced by mono-exponential fit of 8 echoes from a multi-echo gradient-echo (mGRE) sequence (TR/TE/ΔTE=32.2/3.2/3.6ms, flip angle=15°, FOV=256x256mm, 1mm isotropic resolution). Its complex phase data was used to produce an auxiliary field map to correct small susceptibility induced distortions in all images, including itself (Fleysher et al., 2018). Maps of MWF and T2* were registered to T1W MP-RAGE (TR/TI/TE=2100/800/2.8ms, flip angle=8°, FOV=240x240x220mm, 1mm isotropic resolution) over which anatomical regions were delineated using WMPARC module of FreeSurfer, version 7 (Fischl, 2012). MWF and T2* values were averaged over globus pallidus, corpus callosum, white matter (excluding corpus callosum), deep gray matter (excluding globus pallidus), and cortical gray matter for each individual.

Results:

For each studied brain region, Figure 1 shows average MWF and T2* values arranged in decreasing order of MWF. This ordering happens to correspond to a decreasing order of average value of T2*. Among the regions, globus pallidus shows the largest MWF, larger than the corpus callosum and other white matter, which is inconsistent with its known anatomical composition (Javed & Cascella, 2024). Visually, (Fig. 2) globus pallidus appears significantly brighter than its surroundings in a representative MWF map, and darker in the T2* map, reflecting its shorter T2* time. The globus pallidus is much less distinct on the T1W image, as its T1 is similar to surrounding structures.
Supporting Image: Figure1.png
   ·Myelin water fraction (MWF) and T2* values for different brain regions.
Supporting Image: Figure2.png
   ·Representative T1W, MWF and T2* images.
 

Conclusions:

Globus pallidus is a gray matter structure which contains some myelinated axons. Its myelination, however, is known to be similar to other deep gray matter nuclei and lower than corpus callosum, the largest commissural white matter tract (Fitsiori et al., 2011; Jaeger & Kita, 2011; Javed & Cascella, 2024). MWI showed expected ordering of brain regions by myelin content with the exception of globus pallidus, which also exhibits the shortest T2*. MWF in globus pallidus is therefore likely biased by the effect of its iron on the short T2 component attributed to myelin in the MWI analysis. We focused on healthy individuals, but pathological iron accumulation should be considered as a cause of biased MWF in disease states. Imaging markers sensitive to mesoscopic inhomogeneities, such as T2*, could be used to develop a correction for bias in the MWF estimate.

Novel Imaging Acquisition Methods:

Multi-Modal Imaging 1
Imaging Methods Other 2

Keywords:

MRI
Myelin
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Globus Pallidus

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Other

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

Yes

Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.

Yes, I have IRB or AUCC approval

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Structural MRI
Other, Please specify  -   Myelin Water Imaging

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

FSL
Free Surfer

Provide references using APA citation style.

Birkl, C. et al. (2019). The influence of brain iron on myelin water imaging. NeuroImage, 199, 545–552.
Doucette, J. et al. (2020). DECAES – DEcomposition and Component Analysis of Exponential Signals. Zeitschrift Für Medizinische Physik, 30(4), 271–278.
Fischl, B. (2012). FreeSurfer. NeuroImage, 62(2), 774–781.
Fitsiori, A. et al. (2011). The corpus callosum: white matter or terra incognita. The British Journal of Radiology, 84(997), 5–18.
Fleysher, R. et al. (2018). White matter structural integrity and transcranial Doppler blood flow pulsatility in normal aging. Magnetic Resonance Imaging, 47, 97–102.
Jaeger, D. et al. (2011). Functional connectivity and integrative properties of globus pallidus neurons. Neuroscience, 198, 44–53.
Javed, N. et al. (2024). Neuroanatomy, Globus Pallidus. StatPearls Publishing, Treasure Island (FL).
van der Weijden, C. W. J. et al. (2023). Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status. Brain, 146(4), 1243–1266.

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