Inhomogeneous Magnetization Transfer (ihMT) imaging in the acute cuprizone mouse model of demyelination/remyelination

Hertanu, Andreea; Soustelle, Lucas; Buron, Julie; Priellec, Julie Le; Cayre, Myriam; Troter, Arnaud Le; Prevost, Valentin H.; Ranjeva, Jean Philippe; Varma, Gopal; Alsop, David C.; Durbec, Pascale; Girard, Olivier; Duhamel, Guillaume

doi:10.1016/j.neuroimage.2022.119785

Cited by 4 publications

(3 citation statements)

References 73 publications

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“…For instance, the four‐pool model—recently documented quite comprehensively by Manning et al 62 —considers two exchanging myelin and nonmyelin water pools, respectively exchanging with the myelin and nonmyelin macromolecular matrices. In addition, evidence was found that multiple dipolar order reservoirs exist in myelinated tissues 25 and in synthetized lipid samples representative of myelin, 63 and their intrinsic association to macromolecular Zeeman reservoirs (with respective and distinct MT parameters) has yet to be investigated. Of note, the proposed DOFS‐MTw acquisitions effectively remove the need to consider the dipolar order magnetization reservoirs, and the qMT‐ONRS model remains valid as long as the respective exchange rate and macromolecular T 2,b parameters are considered equal, contrary to the fitting of SOFS‐based acquisitions for which the impact of dipolar order reservoir on the saturation attenuation is less predictable.…”

Section: Discussionmentioning

confidence: 99%

“…However, these early experiments were performed either on agar gel phantoms, which are not representative of the brain tissue and have weak dipolar order effects, 18 or on ex vivo white matter samples at room temperature, 17 which strongly limits the influence of dipolar order on the macromolecular magnetization 19–21 . Recent investigations have shown that myelinated central nervous system tissues are associated with relatively strong dipolar order effects as denoted by a long dipolar order relaxation time (T 1D ; T 1D ≈ 6–10 ms) and as identified by inhomogeneous magnetization transfer (ihMT) imaging in studies with ex vivo (at physiological temperature) and in vivo specimens from animals, such as in mouse brains 22–24 and rat spinal cord, 25 and in humans brains 26–28 . Hence, and given the typical irradiation powers used in clinical MR scanners for pulsed SOFS qMT experiments, the conditions for dipolar order to contribute to the MT signal in in vivo central nervous system tissues can be satisfied 29 .…”

Section: Introductionmentioning

confidence: 99%

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Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

Soustelle

Troalen

Hertanu

et al. 2023

Magnetic Resonance in Med

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To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases. Methods:The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T 1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction[MPF], T 2,f , T 2,b , R, and free pool T 1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T 1 . Results: Bland-Altman analyses demonstrated a systematic underestimation of MPF (−2.5% and −1.3%, on average, in white and gray matter, respectively) and overestimation of T 1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored.Reproducibility of the proposed framework is excellent (ΔMPF = −0.03% and ΔT 1 = −19.0 ms). The single-point methodology yielded consistent MPF and T 1 values with respective maximum relative average bias of −0.15% and −3.5 ms found in white matter. Conclusion:The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

Soustelle

Troalen

Hertanu

et al. 2023

Magnetic Resonance in Med

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“…Efforts are ongoing to explore new sequences to add to our protocol in order to expand the utility of our repository. Currently, inhomogeneous magnetization transfer, which has shown excellent sensitivity for myelin content validated in mice [105,106], is being considered as its applications move from animal models towards human imaging. New adaptations are also being tested to improve scan quality, including custom MR-compatible containers for standardization of brain orientation and to facilitate the use of gentle vacuuming to ensure bubble removal.…”

Section: Future Directionsmentioning

confidence: 99%

Postmortem Brain Imaging in Alzheimer’s Disease and Related Dementias: The South Texas Alzheimer’s Disease Research Center Repository

Li,

Rashid,

et al. 2023

JAD

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Background: Neuroimaging bears the promise of providing new biomarkers that could refine the diagnosis of dementia. Still, obtaining the pathology data required to validate the relationship between neuroimaging markers and neurological changes is challenging. Existing data repositories are focused on a single pathology, are too small, or do not precisely match neuroimaging and pathology findings. Objective: The new data repository introduced in this work, the South Texas Alzheimer’s Disease research center repository, was designed to address these limitations. Our repository covers a broad diversity of dementias, spans a wide age range, and was specifically designed to draw exact correspondences between neuroimaging and pathology data. Methods: Using four different MRI sequences, we are reaching a sample size that allows for validating multimodal neuroimaging biomarkers and studying comorbid conditions. Our imaging protocol was designed to capture markers of cerebrovascular disease and related lesions. Quantification of these lesions is currently underway with MRI-guided histopathological examination. Results: A total of 139 postmortem brains (70 females) with mean age of 77.9 years were collected, with 71 brains fully analyzed. Of these, only 3% showed evidence of AD-only pathology and 76% had high prevalence of multiple pathologies contributing to clinical diagnosis. Conclusion: This repository has a significant (and increasing) sample size consisting of a wide range of neurodegenerative disorders and employs advanced imaging protocols and MRI-guided histopathological analysis to help disentangle the effects of comorbid disorders to refine diagnosis, prognosis and better understand neurodegenerative disorders.

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Magnetic resonance metrics for identification of cuprizone-induced demyelination in the mouse model of neurodegeneration: a review

Friesen,

Hari,

Sheft

et al. 2024

Magn Reson Mater Phy

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Inhomogeneous Magnetization Transfer (ihMT) imaging in the acute cuprizone mouse model of demyelination/remyelination

Cited by 4 publications

References 73 publications

Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

Quantitative magnetization transfer MRI unbiased by on‐resonance saturation and dipolar order contributions

Postmortem Brain Imaging in Alzheimer’s Disease and Related Dementias: The South Texas Alzheimer’s Disease Research Center Repository

Magnetic resonance metrics for identification of cuprizone-induced demyelination in the mouse model of neurodegeneration: a review

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