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Loud acoustic noise from the scanner during functional magnetic resonance imaging (fMRI) can affect functional connectivity (FC) observed in the resting state, but the exact effect of the MRI acoustic noise on resting state FC is not well understood. Functional ultrasound (fUS) is a neuroimaging method that visualizes brain activity based on relative cerebral blood volume (rCBV), a similar neurovascular coupling response to that measured by fMRI, but without the audible acoustic noise. In this study, we investigated the effects of different acoustic noise levels (silent, 80 dB, and 110 dB) on FC by measuring resting state fUS (rsfUS) in awake mice in an environment similar to fMRI measurement. Then, we compared the results to those of resting state fMRI (rsfMRI) conducted using an 11.7 Tesla scanner. RsfUS experiments revealed a significant reduction in FC between the retrosplenial dysgranular and auditory cortexes (0.56 ± 0.07 at silence vs 0.05 ± 0.05 at 110 dB, p=.01) and a significant increase in FC anticorrelation between the infralimbic and motor cortexes (-0.21 ± 0.08 at silence vs -0.47 ± 0.04 at 110 dB, p=.017) as acoustic noise increased from silence to 80 dB and 110 dB, with increased consistency of FC patterns between rsfUS and rsfMRI being found with the louder noise conditions. Event-related auditory stimulation experiments using fUS showed strong positive rCBV changes (16.5% ± 2.9% at 110 dB) in the auditory cortex, and negative rCBV changes (-6.7% ± 0.8% at 110 dB) in the motor cortex, both being constituents of the brain network that was altered by the presence of acoustic noise in the resting state experiments. Anticorrelation between constituent brain regions of the default mode network (such as the infralimbic cortex) and those of task-positive sensorimotor networks (such as the motor cortex) is known to be an important feature of brain network antagonism, and has been studied as a biological marker of brain disfunction and disease. This study suggests that attention should be paid to the acoustic noise level when using rsfMRI to evaluate the anticorrelation between the default mode network and task-positive sensorimotor network., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Functional ultrasound (fUS) imaging is a method for visualizing deep brain activity based on cerebral blood volume changes coupled with neural activity, while functional MRI (fMRI) relies on the blood-oxygenation-level-dependent signal coupled with neural activity. Low-frequency fluctuations (LFF) of fMRI signals during resting-state can be measured by resting-state fMRI (rsfMRI), which allows functional imaging of the whole brain, and the distributions of resting-state network (RSN) can then be estimated from these fluctuations using independent component analysis (ICA). This procedure provides an important method for studying cognitive and psychophysiological diseases affecting specific brain networks. The distributions of RSNs in the brain-wide area has been reported primarily by rsfMRI. RSNs using rsfMRI are generally computed from the time-course of fMRI signals for more than 5 min. However, a recent dynamic functional connectivity study revealed that RSNs are still not perfectly stable even after 10 min. Importantly, fUS has a higher temporal resolution and stronger correlation with neural activity compared with fMRI. Therefore, we hypothesized that fUS applied during the resting-state for a shorter than 5 min would provide similar RSNs compared to fMRI. High temporal resolution rsfUS data were acquired at 10 Hz in awake mice. The quality of the default mode network (DMN), a well-known RSN, was evaluated using signal-noise separation (SNS) applied to different measurement durations of rsfUS. The results showed that the SNS did not change when the measurement duration was increased to more than 210 s. Next, we measured short-duration rsfUS multi-slice measurements in the brain-wide area. The results showed that rsfUS with the short duration succeeded in detecting RSNs distributed in the brain-wide area consistent with RSNs detected by 11.7-T MRI under awake conditions (medial prefrontal cortex and cingulate cortex in the anterior DMN, retrosplenial cortex and visual cortex in the posterior DMN, somatosensory and motor cortexes in the lateral cortical network, thalamus, dorsal hippocampus, and medial cerebellum), confirming the reliability of the RSNs detected by rsfUS. However, bilateral RSNs located in the secondary somatosensory cortex, ventral hippocampus, auditory cortex, and lateral cerebellum extracted from rsfUS were different from the unilateral RSNs extracted from rsfMRI. These findings indicate the potential of rsfUS as a method for analyzing functional brain networks and should encourage future research to elucidate functional brain networks and their relationships with disease model mice., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by q-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination in MS patients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS., Significance Statement: Myelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. In the current study, we introduced a novel MRI modality that produces the "myelin map." The myelin map accurately depicted myelin status in mice and nonhuman primates and in a pilot clinical study of multiple sclerosis patients, suggesting that it is useful in detecting possibly remyelinated lesions. A myelin map of the human brain could be obtained in <10 min using a 3 T scanner and it therefore promises to be a powerful tool for researchers and clinicians examining myelin-related diseases., (Copyright © 2016 the authors 0270-6474/16/362797-13$15.00/0.)

The present study characterized fetal sulcation patterns and gyrification in the cerebrum of the New World monkey group, common marmosets, using a 3D T2-weighted high-resolution anatomical magnetic resonance imaging (MRI) sequence from the fixed brain at 7-tesla ex vivo. Fetal sulcation in the marmoset cerebrum began to indent the lateral fissure and hippocampal sulcus in gestational week (GW) 12, and then the following sulci emerged: the callosal and calcarine sulci on GW 15; the superior temporal sulcus on GW 17; and the circular and occipitotemporal sulci on GW 18. The degree of cortical convolution was evaluated quantitatively based on 2D MRI slices by the gyrification index (GI) and based on 3D MRI data by sulcation index (SI). Both the mean GI and SI increased from GW 16, and were closely correlated with the cortical volume and the cortical surface area during fetal periods (their correlation coefficients marked more than 0.95). After birth, both the mean GI and SI decreased slightly by 2years of age, whereas the cortical volume and surface area continuously increased. Notably, histological analysis showed that the outer subventricular zone (oSVZ) in non-sulcal regions was thicker than that in the presumptive calcarine sulcal region on GW 13, preceding the infolding of the calcarine sulcus. The present results showed definite sulcal infolding on the cerebral cortical surface of the marmosets, with similar pattern and sequence of their emergences to other higher-order primates such as macaques and humans. Differential expansion of the oSVZ may be involved in gyral convolution and sulcal infolding in the developing cerebrum., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

The developmental anatomy of the brain is largely directed by neural-based cues. Despite this knowledge, the developmental trajectory of the primate brain has not yet been fully characterized. To realize this goal, the advance in noninvasive imaging methods and new brain atlases are essential. The common marmoset (Callithrix jacchus), a small New World primate, is widely used in neuroscience research. The recent introduction of transgenic techniques has enabled the marmoset to be used as a genetically modifiable primate model for brain development. Here, a magnetic resonance histology technique involving the use of ultra-high-resolution ex vivo magnetic resonance imaging (MRI) was performed to identify the developmental anatomy of the marmoset brain at different time points from gestational week 8 through to birth. The data allowed the generation of a multidimensional atlas of brain structures at different developmental stages. Furthermore, in utero MRI techniques were developed to noninvasively monitor brain development during the embryonic and fetal stages. The multidimensional atlas and the MRI tools developed herein are anticipated to further our understanding of the developing primate brain., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)