Multiple-mouse magnetic resonance imaging with cryogenic radiofrequency probes for evaluation of brain development

Arbabi, Aryan; Noakes, Leigh Spencer; Vousden, Dulcie A; Dazai, Jun; Spring, Shoshana; Botelho, Owen; Keshavarzian, Tina; Mattingly, Mark A.; Ellegood, Jacob; Nutter, Lauryl M. J.; Wissmann, Ralph; Sled, John G.; Lerch, Jason P.; Henkelman, R. Mark; Nieman, Brian J.

doi:10.1016/j.neuroimage.2022.119008

Cited by 17 publications

(13 citation statements)

References 55 publications

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“…MRI for assessment of brain morphology was performed in vivo at the Mouse Imaging Centre using multiple-mouse MRI, imaging up to four mice simultaneously (Arbabi et al, 2022; Nieman et al, 2018). Twenty-four hours prior to scanning, mice received an intraperitoneal injection of 30 mM MnCl 2 (0.4 mmol per kg; M8054, Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

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A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects

Tillotson

Yan

Ruston

et al. 2023

Preprint

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ATRX is a chromatin remodelling ATPase that is involved in transcriptional regulation, DNA damage repair and heterochromatin maintenance. It has been widely studied for its role in ALT-positive cancers, but its role in neurological function remains elusive. Hypomorphic mutations in the X-linked ATRX gene cause a rare form of intellectual disability combined with alpha-thalassemia called ATR-X syndrome in hemizygous males. Patients also have facial dysmorphism, microcephaly, musculoskeletal defects and genital abnormalities. Since complete deletion of ATRX in mice results in early embryonic lethality, the field has largely relied on conditional knockout models to assess the role of ATRX in multiple tissues. Given that null alleles are not found in patients, a more patient-relevant model was needed. Here, we have produced and characterised the first patient mutation knock-in model of ATR-X syndrome, carrying the most common patient mutation, R246C. This is one of a cluster of missense mutations located in the chromatin interaction domain that disrupts its function. The knock-in mice recapitulate several aspects of the patient disorder, including craniofacial defects, microcephaly and impaired neurological function. They provide a powerful model for understanding the molecular mechanisms underlying ATR-X syndrome and for testing potential therapeutic strategies.

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Section: Methodsmentioning

confidence: 99%

Section: Magnetic Resonance Imaging (Mri)mentioning

confidence: 99%

A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects

Tillotson

Yan

Ruston

et al. 2023

Preprint

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“…A 7-Tesla 306 mm horizontal-bore magnet (BioSpec 70/30 USR, Bruker) with a ParaVision 6.0.1 console ( 55 ) was used to image brains in skulls. Eight samples were imaged in parallel using a custom-built 8-coil solenoid array.…”

Section: Methodsmentioning

confidence: 99%

Age-dependent gray matter demyelination is associated with leptomeningeal neutrophil accumulation

et al. 2022

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People living with multiple sclerosis (MS) experience episodic CNS white matter lesions instigated by autoreactive T cells. With age, patients with MS show evidence of gray matter demyelination and experience devastating nonremitting symptomology. What drives progression is unclear and studying this has been hampered by the lack of suitable animal models. Here, we show that passive experimental autoimmune encephalomyelitis (EAE) induced by an adoptive transfer of young Th17 cells induced a nonremitting clinical phenotype that was associated with persistent leptomeningeal inflammation and cortical pathology in old, but not young, SJL/J mice. Although the quantity and quality of T cells did not differ in the brains of old versus young EAE mice, an increase in neutrophils and a decrease in B cells were observed in the brains of old mice. Neutrophils were also found in the leptomeninges of a subset of progressive MS patient brains that showed evidence of leptomeningeal inflammation and subpial cortical demyelination. Taken together, our data show that while Th17 cells initiate CNS inflammation, subsequent clinical symptoms and gray matter pathology are dictated by age and associated with other immune cells, such as neutrophils.

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“…Owing to the small number of proton spins in microscopic tissue sample volumes, the signal-tonoise ratio (SNR) is low in MR microscopy. Extensive research has been conducted on the design of radiofrequency (RF) coils for MR microscopy [8], and several types of coils have been proposed, including surface [9,10], flat-histology [3], birdcage [11], Helmholtz [12], and solenoid coils [1,[13][14][15][16][17][18]. Among these, the flat histology coil based on a single-turn inductor [3] and the solenoid coil have a high filling factor, high uniformity of RF transmission (B1 + ) field, and high SNR within the imaging volume.…”

Section: Introductionmentioning

confidence: 99%

Multiturn Planar Inductor for the Improvement of Signal-to-Noise Ratio Response in Magnetic Resonance Microscopy

et al. 2022

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In this study, we propose a novel, multiturn histology coil for microscopic magnetic resonance (MR) imaging of histological tissue slices with substantially higher signal-to-noise-ratio (SNR) outcomes compared with previously developed coils. We performed electromagnetic simulations of the proposed coils and acquired MR images from a gelatin phantom and a rat brain slice with the implemented coils. The performances of the coils were evaluated by comparing the measured and simulated radio-frequency transmission (B1 + ) fields in a flip-angle map form, and with low flip-angle gradient echo images to calculate the SNR increase as a function of the number of turns (n) of the coils. This study was performed on a 3 T MR imaging system. The proposed coil with n = 7 achieved SNR greater than 3.5 times that of a single-turn coil while preserving the highly uniform B1 + field across the imaging region. The proposed method provides new possibilities for high-resolution MR imaging of microscopic tissue samples for biomedical applications.INDEX TERMS magnetic resonance imaging (MRI), microscopy, signal-to-noise ratio (SNR), radiofrequency (RF), Multiturn planar inductor (MTPI)

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Multiple-mouse magnetic resonance imaging with cryogenic radiofrequency probes for evaluation of brain development

Cited by 17 publications

References 55 publications

A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects

A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects

Age-dependent gray matter demyelination is associated with leptomeningeal neutrophil accumulation

Multiturn Planar Inductor for the Improvement of Signal-to-Noise Ratio Response in Magnetic Resonance Microscopy

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