Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study

Laura C. Bell; Alberto E. Fuentes; Deborah R. Healey; Renee Chao; Nadine Bakkar; Rachael W. Sirianni; David X. Medina; Robert P. Bowser; Shafeeq S. Ladha; Natenael B. Semmineh; Ashley M. Stokes; C. Chad Quarles

doi:10.1016/j.mri.2021.10.036

Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study

Laura C. Bell, Alberto E. Fuentes, Deborah R. Healey, Renee Chao, Nadine Bakkar, Rachael W. Sirianni, David X. Medina, Robert P. Bowser, Shafeeq S. Ladha, Natenael B. Semmineh, Ashley M. Stokes, C. Chad Quarles

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

T₂^⁎ relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease. We observed a statistically significant decrease in TRATE over time in the gastrocnemius, tibialis, and digital flexor muscles in the SOD1-G93A model (p-value = 0.003, 0.008, 0.005; respectively), whereas TRATE did not change over time in the control group (p-value = 0.4777, 0.6837, 0.9682; respectively). Immunofluorescent staining revealed a decrease in minimum fiber area and cell density in the SOD1-G93A model when compared to the control group (p-value = 6.043E-10 and 2.265E-10, respectively). These microstructural changes observed from histology align with the theorized biophysical properties of TRATE. We demonstrate that TRATE can longitudinally differentiate disease associated atrophy from healthy muscle and has potential to serve as a biomarker for disease progression and ultimately therapy response in patients with ALS.

Original language	English (US)
Pages (from-to)	217-221
Number of pages	5
Journal	Magnetic Resonance Imaging
Volume	85
DOIs	https://doi.org/10.1016/j.mri.2021.10.036
State	Published - Jan 2022
Externally published	Yes

Keywords

ALS
MRI
Muscle imaging
Perfusion imaging
Relaxivity imaging

ASJC Scopus subject areas

Biophysics
Biomedical Engineering
Radiology Nuclear Medicine and imaging

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10.1016/j.mri.2021.10.036

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Bell, L. C., Fuentes, A. E., Healey, D. R., Chao, R., Bakkar, N., Sirianni, R. W., Medina, D. X., Bowser, R. P., Ladha, S. S., Semmineh, N. B., Stokes, A. M., & Quarles, C. C. (2022). Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study. Magnetic Resonance Imaging, 85, 217-221. https://doi.org/10.1016/j.mri.2021.10.036

Bell, LC, Fuentes, AE, Healey, DR, Chao, R, Bakkar, N, Sirianni, RW, Medina, DX, Bowser, RP, Ladha, SS, Semmineh, NB, Stokes, AM & Quarles, CC 2022, 'Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study', Magnetic Resonance Imaging, vol. 85, pp. 217-221. https://doi.org/10.1016/j.mri.2021.10.036

@article{461e9484c10047e1b82b807b34bfd5d8,

title = "Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study",

abstract = "T2⁎ relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease. We observed a statistically significant decrease in TRATE over time in the gastrocnemius, tibialis, and digital flexor muscles in the SOD1-G93A model (p-value = 0.003, 0.008, 0.005; respectively), whereas TRATE did not change over time in the control group (p-value = 0.4777, 0.6837, 0.9682; respectively). Immunofluorescent staining revealed a decrease in minimum fiber area and cell density in the SOD1-G93A model when compared to the control group (p-value = 6.043E-10 and 2.265E-10, respectively). These microstructural changes observed from histology align with the theorized biophysical properties of TRATE. We demonstrate that TRATE can longitudinally differentiate disease associated atrophy from healthy muscle and has potential to serve as a biomarker for disease progression and ultimately therapy response in patients with ALS.",

keywords = "ALS, MRI, Muscle imaging, Perfusion imaging, Relaxivity imaging",

author = "Bell, {Laura C.} and Fuentes, {Alberto E.} and Healey, {Deborah R.} and Renee Chao and Nadine Bakkar and Sirianni, {Rachael W.} and Medina, {David X.} and Bowser, {Robert P.} and Ladha, {Shafeeq S.} and Semmineh, {Natenael B.} and Stokes, {Ashley M.} and Quarles, {C. Chad}",

note = "Funding Information: Flinn Foundation (LCB, AEF, DRH, CCQ) , Barrow Neurological Foundation (AMS) , Department of Defense W81XWH-14-0311 (RWS) , Fulton Family Foundation , grant number 3032285 (RPB,SSL), ALS Association , grant number 8032198 (RPB,SSL). Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2022",

month = jan,

doi = "10.1016/j.mri.2021.10.036",

language = "English (US)",

volume = "85",

pages = "217--221",

journal = "Magnetic Resonance Imaging",

issn = "0730-725X",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE)

T2 - A preliminary study

AU - Bell, Laura C.

AU - Fuentes, Alberto E.

AU - Healey, Deborah R.

AU - Chao, Renee

AU - Bakkar, Nadine

AU - Sirianni, Rachael W.

AU - Medina, David X.

AU - Bowser, Robert P.

AU - Ladha, Shafeeq S.

AU - Semmineh, Natenael B.

AU - Stokes, Ashley M.

AU - Quarles, C. Chad

N1 - Funding Information: Flinn Foundation (LCB, AEF, DRH, CCQ) , Barrow Neurological Foundation (AMS) , Department of Defense W81XWH-14-0311 (RWS) , Fulton Family Foundation , grant number 3032285 (RPB,SSL), ALS Association , grant number 8032198 (RPB,SSL). Publisher Copyright: © 2021 Elsevier Inc.

PY - 2022/1

Y1 - 2022/1

N2 - T2⁎ relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease. We observed a statistically significant decrease in TRATE over time in the gastrocnemius, tibialis, and digital flexor muscles in the SOD1-G93A model (p-value = 0.003, 0.008, 0.005; respectively), whereas TRATE did not change over time in the control group (p-value = 0.4777, 0.6837, 0.9682; respectively). Immunofluorescent staining revealed a decrease in minimum fiber area and cell density in the SOD1-G93A model when compared to the control group (p-value = 6.043E-10 and 2.265E-10, respectively). These microstructural changes observed from histology align with the theorized biophysical properties of TRATE. We demonstrate that TRATE can longitudinally differentiate disease associated atrophy from healthy muscle and has potential to serve as a biomarker for disease progression and ultimately therapy response in patients with ALS.

AB - T2⁎ relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease. We observed a statistically significant decrease in TRATE over time in the gastrocnemius, tibialis, and digital flexor muscles in the SOD1-G93A model (p-value = 0.003, 0.008, 0.005; respectively), whereas TRATE did not change over time in the control group (p-value = 0.4777, 0.6837, 0.9682; respectively). Immunofluorescent staining revealed a decrease in minimum fiber area and cell density in the SOD1-G93A model when compared to the control group (p-value = 6.043E-10 and 2.265E-10, respectively). These microstructural changes observed from histology align with the theorized biophysical properties of TRATE. We demonstrate that TRATE can longitudinally differentiate disease associated atrophy from healthy muscle and has potential to serve as a biomarker for disease progression and ultimately therapy response in patients with ALS.

KW - ALS

KW - MRI

KW - Muscle imaging

KW - Perfusion imaging

KW - Relaxivity imaging

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U2 - 10.1016/j.mri.2021.10.036

DO - 10.1016/j.mri.2021.10.036

M3 - Article

C2 - 34715291

AN - SCOPUS:85118224165

SN - 0730-725X

VL - 85

SP - 217

EP - 221

JO - Magnetic Resonance Imaging

JF - Magnetic Resonance Imaging

ER -

Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study

Abstract

Keywords

ASJC Scopus subject areas

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