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Previous studies of operant learning have addressed neuronal activities and network changes in specific brain areas, such as the striatum, sensorimotor cortex, prefrontal/orbitofrontal cortices, and hippocampus. However, how changes in the whole-brain network are caused by cellular-level changes remains unclear. We, therefore, combined resting-state functional magnetic resonance imaging (rsfMRI) and whole-brain immunohistochemical analysis of early growth response 1 (EGR1), a marker of neural plasticity, to elucidate the temporal and spatial changes in functional networks and underlying cellular processes during operant learning. We used an 11.7-Tesla MRI scanner and whole-brain immunohistochemical analysis of EGR1 in mice during the early and late stages of operant learning. In the operant training, mice received a reward when they pressed left and right buttons alternately, and were punished with a bright light when they made a mistake. A group of mice (n = 22) underwent the first rsfMRI acquisition before behavioral sessions, the second acquisition after 3 training-session-days (early stage), and the third after 21 training-session-days (late stage). Another group of mice (n = 40) was subjected to histological analysis 15 min after the early or late stages of behavioral sessions. Functional connectivity increased between the limbic areas and thalamus or auditory cortex after the early stage of training, and between the motor cortex, sensory cortex, and striatum after the late stage of training. The density of EGR1-immunopositive cells in the motor and sensory cortices increased in both the early and late stages of training, whereas the density in the amygdala increased only in the early stage of training. The subcortical networks centered around the limbic areas that emerged in the early stage have been implicated in rewards, pleasures, and fears. The connectivities between the motor cortex, somatosensory cortex, and striatum that consolidated in the late stage have been implicated in motor learning. Our multimodal longitudinal study successfully revealed temporal shifts in brain regions involved in behavioral learning together with the underlying cellular-level plasticity between these regions. Our study represents a first step towards establishing a new experimental paradigm that combines rsfMRI and immunohistochemistry to link macroscopic and microscopic mechanisms involved in learning., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemogenetic approaches employing ligand-gated ion channels are advantageous regarding manipulation of target neuronal population functions independently of endogenous second messenger pathways. Among them, Ionotropic Receptor (IR)-mediated neuronal activation (IRNA) allows stimulation of mammalian neurons that heterologously express members of the insect chemosensory IR repertoire in response to their cognate ligands. In the original protocol, phenylacetic acid, a ligand of the IR84a/IR8a complex, was locally injected into a brain region due to its low permeability of the blood-brain barrier. To circumvent this invasive injection, we sought to develop a strategy of peripheral administration with a precursor of phenylacetic acid, phenylacetic acid methyl ester, which is efficiently transferred into the brain and converted to the mature ligand by endogenous esterase activities. This strategy was validated by electrophysiological, biochemical, brain-imaging, and behavioral analyses, demonstrating high utility of systemic IRNA technology in the remote activation of target neurons in the brain., (© 2024. The Author(s).)

Adult neurogenesis confers the hippocampus with unparalleled neural plasticity, essential for intricate cognitive functions. The specific influence of sparse newborn neurons (NBNs) in modulating neural activities and subsequently steering behavior, however, remains obscure. Using an engineered NBN-tetanus toxin mouse model (NBN-TeTX), we noninvasively silenced NBNs, elucidating their crucial role in impulse inhibition and cognitive flexibility as evidenced through Morris water maze reversal learning and Go/Nogo task in operant learning. Task-based functional MRI (tb-fMRI) paired with operant learning revealed dorsal hippocampal hyperactivation during the Nogo task in male NBN-TeTX mice, suggesting that hippocampal hyperexcitability might underlie the observed behavioral deficits. Additionally, resting-state fMRI (rs-fMRI) exhibited enhanced functional connectivity between the dorsal and ventral dentate gyrus following NBN silencing. Further investigations into the activities of PV + interneurons and mossy cells highlighted the indispensability of NBNs in maintaining the hippocampal excitation/inhibition balance. Our findings emphasize that the neural plasticity driven by NBNs extensively modulates the hippocampus, sculpting inhibitory control and cognitive flexibility.

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.)

Characterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques., (© 2023. The Author(s).)

Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12 weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aims to assess the usefulness of diffusion tensor imaging (DTI) as a noninvasive method for the evaluation of histological grade and lymph node metastasis in patients with oral carcinoma (OC)., Materials and Methods: Thirty-six consecutive patients with histologically confirmed OC underwent examination by 3-T MRI. DTI was performed using a single-shot echo-planar imaging sequence with b values of 0 and 1000 s/mm 2 and motion-probing gradients in 12 noncollinear directions. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) maps were compared with histopathological findings. The DTI parameters were correlated with the histological grade of the OCs based on the World Health Organization grading criteria and the presence or absence of lymph node metastasis., Results: The FA values (0.275 ± 0.058) of OC were significantly lower than those of normal tongue, muscle, and parotid glands (P < 0.001 for all), and the MD, AD, and RD values (1.220 ± 0.149, 1.434 ± 0.172, and 1.019 ± 0.165 × 10 -3  mm 2 /s, respectively) were significantly higher than their respective normal values (P < 0.001 for all). Significant inverse correlations with histological grades were shown for FA, MD, AD, and RD values in OC patients (r = -0.862, r = -0.797, r = -0.747, and r = -0.844, respectively; P < 0.001 for all). In addition, there was a significant difference in the FA values of metastatic and nonmetastatic lymph nodes (0.186 vs. 0.276), MD (0.923 vs. 1.242 × 10 -3  mm 2 /s), AD (1.246 vs. 1.621 × 10 -3  mm 2 /s), and RD (0.792 vs. 1.100 × 10 -3  mm 2 /s; P < 0.001 for all)., Conclusions: DTI may be clinically useful for the noninvasive evaluation of histological grade and lymph node metastasis in OC patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening disease characterized by the uncontrolled proliferation of EBV-infected T/NK cells with resultant immune system failure against EBV. While a CD5 - HLA-DR + CD8 + T-cell population was previously shown to be EBV-infected cells and a useful marker for monitoring the response to treatment of EBV-HLH, changes in other lymphocyte subsets associated with EBV-HLH treatments have not been closely studied. We herein report a 25-year-old woman with EBV-HLH who presented with a fever, liver failure, and pancytopenia. CD8 + T cells harbored EBV. After failing steroid pulse therapy, one course of CHOP therapy immediately improved her fever and laboratory data and reduced the population of EBV-infected cells. Although the number of EBV-infected cells increased on day 20 of CHOP, a sharp increase in NK cells and normal activated T cells ensued, and the infected cells disappeared without an additional CHOP cycle. She has maintained remission without complications. This rapid immune reconstitution has not been observed in two other patients treated with HLH-2004 protocol-like regimens including prolonged immunosuppressants and etoposide. One cycle of CHOP was thought to have induced the resolution of EBV-HLH by eliminating infected cells as well as inducing the reconstruction of anti-EBV immunity.

The ability of animals to retrieve memories stored in response to the environment is essential for behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear. Here, we developed a novel chemogenetic activation strategy exploiting insect olfactory ionotropic receptors (IRs), termed "IR-mediated neuronal activation," and used it for selective stimulation of NE neurons in the locus coeruleus (LC). Drosophila melanogaster IR84a and IR8a subunits were expressed in LC NE neurons in transgenic mice. Application of phenylacetic acid (a specific ligand for the IR84a/IR8a complex) at appropriate doses induced excitatory responses of NE neurons expressing the receptors in both slice preparations and in vivo electrophysiological conditions, resulting in a marked increase of NE release in the LC nerve terminal regions (male and female). Ligand-induced activation of LC NE neurons enhanced the retrieval process of conditioned taste aversion without affecting taste sensitivity, general arousal state, and locomotor activity. This enhancing effect on taste memory retrieval was mediated, in part, through α 1 - and β-adrenergic receptors in the basolateral nucleus of the amygdala (BLA; male). Pharmacological inhibition of LC NE neurons confirmed the facilitative role of these neurons in memory retrieval via adrenergic receptors in the BLA (male). Our findings indicate that the LC NE system, through projections to the BLA, controls the retrieval process of taste associative memory. SIGNIFICANCE STATEMENT Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation, but the role of the NE system in memory retrieval remains unclear. We developed a chemogenetic activation system based on insect olfactory ionotropic receptors and used it for selective stimulation of NE neurons in the locus coeruleus (LC) in transgenic mice. Ligand-induced activation of LC NE neurons enhanced the retrieval of conditioned taste aversion, which was mediated, in part, through adrenoceptors in the basolateral amygdala. Pharmacological blockade of LC activity confirmed the facilitative role of these neurons in memory retrieval. Our findings indicate that the LC-amygdala pathway plays an important role in the recall of taste associative memory., (Copyright © 2020 the authors.)

Study Design: Cross-sectional study., Objective: Patients who undergo intramedullary spinal surgery occasionally experience post-surgical chronic pain; however, the underlying mechanisms are not yet completely understood. Therefore, this study aimed to identify the cerebral structural changes in patients with post-surgical chronic myelopathic pain using voxel-based morphometry., Setting: Single university hospital in Tokyo, Japan., Methods: Forty-nine patients who had undergone intramedullary spinal surgery between January 2002 and April 2014 participated in this study. Participants were classified into two groups based on their post-surgical chronic pain intensity: control (numeric rating scale score of <3) and pain (numeric rating scale score of ≥3) groups. We compared pain questionnaire and brain MRI between two groups. Brain MRI data of each participants was analyzed using voxel-based morphometry., Results: Voxel-based morphometry revealed that the gray matter volume in the left supplementary motor area, left primary motor area, and left posterior cingulate cortex was higher in the pain group than that in the control group. In addition, the numeric rating scale score was significantly correlated with increased gray matter volume in the left primary motor area, left posterior cingulate cortex, and right superior parietal lobule., Conclusion: Present study elucidates the characteristic cerebral structural changes after an intramedullary spinal surgery using voxel-based morphometry and indicates that the structural changes in specific cerebral areas are associated with post-surgical chronic myelopathic pain.

Baseline locomotion and behavioral traits in the common marmoset Parkinson's disease model were examined to provide basic information for preclinical evaluations of medical treatments. A single regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine at a cumulative dose of 5 mg/kg as the free base over three consecutive days was administered subcutaneously to 10 marmosets. Data obtained from these marmosets were compared to pre-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine levels or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine free marmosets. After the single regimen, reduced daily locomotion, a measure of immobility (a primary sign of Parkinsonism), was observed for more than a year. A moving tremor was also observed by visual inspection during this period. When apomorphine (0.13 mg/kg, s.c.) was administered, either right or left circling behavior was observed in a cylindrical chamber in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets, suggestive of unequal neural damage between the two brain hemispheres to different extents. MRI revealed that T1 relaxation time in the right substantia nigra correlated with right circling in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets. Histology was supportive of dopaminergic neural loss in the striatum. These results increase our understanding of the utility and limitations of the Parkinson's disease model in marmosets with a single 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine regimen, and provide reference data for efficacious preclinical evaluations.

Background: Skeletal muscles include fast and slow muscle fibers. The tibialis anterior muscle (TA) is mainly composed of fast muscle fibers, whereas the soleus muscle (SOL) is mainly composed of slow muscle fibers. However, a noninvasive approach for appropriately investigating the characteristics of muscles is not available. Monitoring of skeletal muscle characteristics can help in the evaluation of the effects of strength training and diseases on skeletal muscles., Purpose: The present study aimed to determine whether q-space imaging can distinguish between TA and SOL in in vivo mice., Methods: In vivo magnetic resonance imaging of the right calves of mice (n = 8) was performed using a 7-Tesla magnetic resonance imaging system with a cryogenic probe. TA and SOL were assessed. q-space imaging was performed with a field of view of 10 mm × 10 mm, matrix of 48 × 48, and section thickness of 1000 μm. There were ten b-values ranging from 0 to 4244 s/mm2, and each b-value had diffusion encoding in three directions. Magnetic resonance imaging findings were compared with immunohistological findings., Results: Full width at half maximum and Kurtosis maps of q-space imaging showed signal intensities consistent with immunohistological findings for both fast (myosin heavy chain II) and slow (myosin heavy chain I) muscle fibers. With regard to quantification, both full width at half maximum and Kurtosis could represent the immunohistological findings that the cell diameter of TA was larger than that of SOL (P < 0.01)., Conclusion: q-space imaging could clearly differentiate TA from SOL using differences in cell diameters. This technique is a promising method to noninvasively estimate the fiber type ratio in skeletal muscles, and it can be further developed as an indicator of muscle characteristics., Competing Interests: Daisuke Nakashima and Yasushi Sera are directors of Grace imaging Inc. There are no patents, products in development or marketed products associated with this research to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Background: Precise imaging of nerves have been challenging in the head and neck region, mainly due to low spatial resolution. Here, we investigated how nerves in the head and neck region could be visualized using an ultra-high magnetic field MR system., Methods: We used formol-carbol-fixed human cadaveric necks and obtained MR diffusion tensor images (DTIs) using a 9.4 Tesla (T) ultra-high magnetic field MR system. Afterward, we prepared tissue sections and checked the anatomic relationships between the neurons and the carotid artery in order to confirm that the visualized fibers are indeed neuron fibers., Results: We were able to identify nerves, including the vagus nerve, the hypoglossal nerve, and the spinal-accessory nerve. Hematoxylin-eosin stained histological sections confirmed neuron fibers in the same anatomic position., Conclusion: This technique has the feasibility to be applied for a more accurate anatomic understanding, maybe even close to a histological level., (© 2018 The Authors Head & Neck Published by Wiley Periodicals, Inc.)

Background: Although the prognosis of colorectal carcinoma (CRC) patients depends on the histologic grade (HG) and lymph node metastasis (LNM), accurate preoperative assessment of these prognostic factors is often difficult., Purpose: To assess the HG and extent of LNM by q-space imaging (QSI) for preoperative diagnosis of CRC., Study Type: Prospective., Specimen: A total of 20 colorectal tissue samples containing adenocarcinomas and resected lymph nodes (LNs)., Field Strength/sequence: QSI was performed with a 3T MRI system using a diffusion-weighted echo-planar imaging sequence: repetition time, 10,000 msec; echo time, 216 or 210 msec; field of view, 113 × 73.45 mm; matrix, 120 × 78; section thickness, 4 mm; and 11 b values ranging from 0 to 9000 s/mm 2 ., Assessment: The mean displacement (MDP; μm), zero-displacement probability (ZDP; arbitrary unit [a.u.]), kurtosis (K; a.u.), and apparent diffusion coefficient (ADC) were analyzed by two observers and compared with histopathologic findings., Statistical Tests: Spearman's rank correlation coefficient, Mann-Whitney U-test, and ROC curve analyses., Results: For all 20 carcinomas, the MDP, ZDP, K, and ADC were 8.87 ± 0.37 μm, 82.0 ± 6.2 a.u., 74.3 ± 3.0 a.u., and 0.219 ± 0.040 × 10 -3 mm 2 /s, respectively. The MDP (r = -0.768; P < 0.001), ZDP (r = 0.768; P < 0.001), and K (r = 0.785; P < 0.001) were significantly correlated with the HG of CRC, but not the ADC (r = 0.088; P = 0.712). There were also significant differences in the MDP, ZDP, and K between metastatic and nonmetastatic LNs (all, P < 0.001), but not the ADC (P = 0.082). In the HG of CRC and LNM, the area under the curve was significantly greater for MDP, ZDP, and K than for ADC., Data Conclusion: QSI provides useful diagnostic information to assess the HG and extent of LNM in CRC., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1059-1068., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: In this study, we aimed to determine the usefulness of diffusion kurtosis imaging (DKI) as a noninvasive method for evaluation of the histologic grade and lymph node metastasis in patients with oral carcinoma., Materials and Methods: Twenty-seven patients with oral carcinoma were examined with a 3-T MR system and 16-channel coil. DKI data were obtained by a single-shot echo-planar imaging sequence with repetition time, 10,000 ms; echo time, 94 ms; field of view, 250 × 204.25 ms; matrix, 120 × 98; section thickness, 4 mm; four b values of 0, 500, 1000, and 2000 s/mm 2 ; and motion-probing gradients in three orthogonal directions. Diffusivity (D) and kurtosis (K) were calculated using the equation: S = S 0 ∙ exp(-b ∙ D + b 2 ∙ D 2 ∙ K/6). Conventional apparent diffusion coefficient (ADC) was also calculated. The MR images were compared with the histopathologic findings., Results: Relative to the histologic grades (Grades 1, 2, and 3) of the 27 oral carcinomas, D values showed a significant inverse correlation (r = -0.885; P < 0.001) and K values showed a significant positive correlation (r = 0.869; P < 0.001), whereas ADC values showed no significant correlation (r = -0.311; P = 0.115). When comparing between metastatic and non-metastatic lymph nodes, significant differences in the D values (P < 0.001) and K values (P < 0.001), but not the ADC values (P = 0.110) became apparent., Conclusions: In patients with oral carcinoma, DKI seems to be clinically useful for the evaluation of histologic grades and lymph node metastasis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We present a new 3D digital brain atlas of the non-human primate, common marmoset monkey (Callithrix jacchus), with MRI and coregistered Nissl histology data. To the best of our knowledge this is the first comprehensive digital 3D brain atlas of the common marmoset having normalized multi-modal data, cortical and sub-cortical segmentation, and in a common file format (NIfTI). The atlas can be registered to new data, is useful for connectomics, functional studies, simulation and as a reference. The atlas was based on previously published work but we provide several critical improvements to make this release valuable for researchers. Nissl histology images were processed to remove illumination and shape artifacts and then normalized to the MRI data. Brain region segmentation is provided for both hemispheres. The data is in the NIfTI format making it easy to integrate into neuroscience pipelines, whereas the previous atlas was in an inaccessible file format. We also provide cortical, mid-cortical and white matter boundary segmentations useful for visualization and analysis.

Morphometry studies of human brain development have revealed characteristics of some growth patterns, such as gray matter (GM) and white matter (WM), but the features that make human neurodevelopment distinct from that in other species remain unclear. Studies of the common marmoset (Callithrix jacchus), a small New World primate, can provide insights into unique features such as cooperative behaviors complementary to those from comparative analyses using mouse and rhesus monkey. In the present study, we analyzed developmental patterns of GM, WM, and cortical regions with volume measurements using longitudinal sample (23 marmosets; 11 male, 12 female) between the ages of one and 30months. Regional analysis using a total of 164 magnetic resonance imaging datasets revealed that GM volume increased before puberty (5.4months), but subsequently declined until adulthood, whereas WM volume increased rapidly before stabilizing around puberty (9.9months). Cortical regions showed similar patterns of increase and decrease, patterns with global GM but differed in the timing of volume peak and degree of decline across regions. The progressive-regressive pattern detected in both global and cortical GM was well correlated to phases of synaptogenesis and synaptic pruning reported in previous marmoset studies. A rapid increase in WM in early development may represent a distinctive aspect of human neurodevelopment. These findings suggest that studies of marmoset brain development can provide valuable comparative information that will facilitate a deeper understanding of human brain growth and neurodevelopmental disorders., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: In this study, we aimed to evaluate the feasibility of determining the mural invasion depths of colorectal carcinomas using high-spatial-resolution (HSR) quantitative T2 mapping on a 3-T magnetic resonance (MR) scanner., Materials and Methods: Twenty colorectal specimens containing adenocarcinomas were imaged on a 3-T MR system equipped with a 4-channel phased-array surface coil. HSR quantitative T2 maps were acquired using a spin-echo sequence with a repetition time/echo time of 7650/22.6-361.6ms (16 echoes), 87×43.5-mm field of view, 2-mm section thickness, 448×224 matrix, and average of 1. HSR fast-spin-echo T2-weighted images were also acquired. Differences between the T2 values (ms) of the tumor tissue, colorectal wall layers, and fibrosis were measured, and the MR images and histopathologic findings were compared., Results: In all specimens (20/20, 100%), the HSR quantitative T2 maps clearly depicted an 8-layer normal colorectal wall in which the T2 values of each layer differed from those of the adjacent layer(s) (P<0.001). Using this technique, fibrosis (73.6±9.4ms) and tumor tissue (104.2±6.4ms) could also be clearly differentiated (P<0.001). In 19 samples (95%), the HSR quantitative T2 maps and histopathologic data yielded the same findings regarding the tumor invasion depth., Conclusions: Our results indicate that 3-T HSR quantitative T2 mapping is useful for distinguishing colorectal wall layers and differentiating tumor and fibrotic tissues. Accordingly, this technique could be used to determine mural invasion by colorectal carcinomas with a high level of accuracy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 μm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.

Background: Cholinergic cell loss in the basal forebrain, the major source of hippocampal cholinergic projections, has been implicated in Alzheimer's disease., Objective: To examine whether the septohippocampal pathway is involved in tauopathy model mice and to elucidate the tau-associated mechanism underlying cholinergic alteration., Methods: Adult (6 to 8 months old) and old (16 to 18 months old) transgenic mice expressing wild-type human tau, Tg601, were examined using Ex vivo diffusion tensor magnetic resonance imaging (DTI) and 2-[18F]fluoro- 2-deoxy-D-glucose positron emission tomography (FDG-PET). Choline acetyltransferase (ChAT)-positive neurons in the medial septum (MS) were counted by stereological methods. Acetylcholinesterase (AChE) activity and AChE mRNA in 6 brain regions were measured., Results: Ex vivo DTI revealed that the number of fractional anisotropy (FA) streamlines in the septohippocampal tract decreased with age in Tg601 mice. The FA value in the septum was lower in old Tg601 mice than in non-tg mice. A voxel-based statistical analysis of FDG-PET revealed the presence of low glucose uptake areas, involving the MS in adults, and spread over regions including the hippocampal dentate gyrus in old mice. In the MS, the number of choline acetyltransferase (ChAT)-positive neurons decreased in old Tg601 mice. AChE activity and AChE mRNA T transcripts were exclusively higher in the septum., Conclusion: The upregulation of AChE in the septum may result in the selective degeneration of the septohippocampal cholinergic pathway in the tauopathy mouse model.

Astrocytes have recently been shown to provide physiological support for various brain functions, although little is known about their involvement in white matter integrity. Several inherited infantile-onset leukoencephalopathies, such as Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts (MLC), implicate astrocytic involvement in the formation of white matter. Several mouse models of MLC had been generated by knocking out the Mlc1 gene; however, none of those models was reported to show myelin abnormalities prior to formation of the myelin sheath. Here we generated a new Mlc1 knockout mouse and a Mlc1 overexpressing mouse, and demonstrate that astrocyte-specific Mlc1 overexpression causes infantile-onset abnormalities of the white matter in which astrocytic swelling followed by myelin membrane splitting are present, whereas knocking out Mlc1 does not, and only shows myelin abnormalities after 12 months of age. Biochemical analyses demonstrated that MLC1 interacts with the Na + /K + ATPase and that overexpression of Mlc1 results in decreased activity of the astrocytic Na + /K + pump. In contrast, no changes in Na + /K + pump activity were observed in Mlc1 KO mice, suggesting that the reduction in Na + /K + pump activity resulting from Mlc1 overexpression causes astrocytic swelling. Our infantile-onset leukoencephalopathy model based on Mlc1 overexpression may provide an opportunity to further explore the roles of astrocytes in white matter development and structural integrity. We established a novel mouse model for infantile-onset leukoencephalopathy by the overexpression of Mlc1. Mlc1 overexpression reduced activity of the astrocytic sodium pump, which may underlie white matter edema followed by myelin membrane splitting. GLIA 2016 GLIA 2017;65:150-168., (© 2016 Wiley Periodicals, Inc.)

Allodynia, a form of neuropathic pain, is defined as pain in response to a non-nociceptive stimulus. The brain regions responsible for pain, which are not normally activated, can be activated in allodynic mice by providing a suitable stimulus to Aβ-fibers, which transmit signals from tactile sensory fibers. Functional MRI (fMRI) can be used to objectively observe abnormal brain activation. In the present study, fMRI was conducted to investigate allodynia in mice; allodynia was generated by surgical injury at the L4 spinal nerve root, thus selectively stimulating sensory nerve fibers. In intact mice, only the primary somatosensory cortex (S1) was activated by stimulation of Aβ-fibers. Meanwhile, allodynic mice showed significantly higher BOLD signals in the anterior cingulate area (ACA) and thalamus. Using resting state fMRI, both degree and eigenvector centrality were significantly decreased in the contralateral S1, clustering coefficient and local efficiency were significantly increased in the ACA, and betweenness centrality was significantly higher in the ventral posterolateral nucleus of the thalamus. These results suggest that the observed abnormal BOLD activation is associated with defects in Aβ-fibers when Aβ-fibers in allodynic mice are selectively stimulated. The objective approach enabled by fMRI can improve our understanding of pathophysiological mechanisms and therapeutic efficacy., Competing Interests: H.O. is a paid scientific consultant for San Bio, Co., Ltd. All other authors declare that they have no competing financial interests.

Purpose: The purpose of this study was to establish the feasibility of q-space imaging (QSI) as a method of assessing the depth of mural invasion, histologic grade, and the presence of lymph node metastasis in gastric carcinomas., Methods: A 7.0 Tesla MR imaging system was used to investigate 20 gastric specimens containing a carcinoma. QSI was performed by using the following parameters: 50-60 mm × 25-30 mm field of view, 2-mm section thickness, 256 × 128 matrix, 10 b values in the 0-7163 s/mm(2) range, which corresponded to q values of 0-1026/cm, and motion-probing gradients perpendicular to the gastric wall. The MR images and the histopathologic findings were then compared., Results: The depth of tumor invasion of the gastric wall in all 20 carcinomas (100%) was established by using mean displacement, zero-displacement probability, and kurtosis maps. The QSI parameters were significantly correlated with the histologic grades of the gastric carcinomas (all P < 0.001). The QSI parameters made it possible to differentiate between metastatic and nonmetastatic lymph nodes (all P = 0.001)., Conclusion: Ex vivo QSI facilitates excellent diagnostics for evaluating gastric carcinomas in terms of mural invasion, histologic grade, and the presence of lymph node metastasis. Magn Reson Med 76:602-612, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, 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.)

Purpose: To determine the feasibility of diffusion-tensor imaging (DTI) and tractography as means of evaluating the depth of mural invasion by gastric carcinomas., Materials and Methods: This study was approved by our institutional review board, and written informed consent was obtained from each patient. Twenty gastric specimens containing a carcinoma were studied with a 7.0-T MR imaging system equipped with a four-channel phased-array surface coil. DTI was performed by using a field of view of 50-60 mm × 25-30 mm, matrix of 256 × 128, section thickness of 1mm, b value of 1000 s/mm2, and motion-probing gradients in seven noncollinear directions. The MR images were compared with the histopathologic findings as the reference standard., Results: In all 20 carcinomas (100%) the diffusion-weighted images, apparent diffusion coefficient (ADC) maps, fractional anisotropy (FA) maps, λ1 maps, and direction-encoded color FA maps made it possible to identify the same depth of tumor invasion of the gastric wall as observed during histopathologic examination. The λ1 maps provided the best contrast between the carcinomas and the layers of the gastric wall. The carcinomas also had lower ADC values and lower FA values than the normal gastric wall; thus, the carcinomas were clearly demarcated from the normal gastric wall. Tractography images were also useful for determining the depth of tumor invasion of the gastric wall., Conclusions: DTI and tractography are feasible means of evaluating gastric specimens and provide excellent diagnostic accuracy for evaluating mural invasion by gastric carcinomas., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Unlabelled: : Previous studies have demonstrated that neural stem/progenitor cells (NS/PCs) promote functional recovery in rodent animal models of spinal cord injury (SCI). Because distinct differences exist in the neuroanatomy and immunological responses between rodents and primates, it is critical to determine the effectiveness and safety of allografted embryonic stem cell (ESC)-derived NS/PCs (ESC-NS/PCs) in a nonhuman primate SCI model. In the present study, common marmoset ESC-NS/PCs were grafted into the lesion epicenter 14 days after contusive SCI in adult marmosets (transplantation group). In the control group, phosphate-buffered saline was injected instead of cells. In the presence of a low-dose of tacrolimus, several grafted cells survived without tumorigenicity and differentiated into neurons, astrocytes, or oligodendrocytes. Significant differences were found in the transverse areas of luxol fast blue-positive myelin sheaths, neurofilament-positive axons, corticospinal tract fibers, and platelet endothelial cell adhesion molecule-1-positive vessels at the lesion epicenter between the transplantation and control groups. Immunoelectron microscopic examination demonstrated that the grafted ESC-NS/PC-derived oligodendrocytes contributed to the remyelination of demyelinated axons. In addition, some grafted neurons formed synaptic connections with host cells, and some transplanted neurons were myelinated by host cells. Eventually, motor functional recovery significantly improved in the transplantation group compared with the control group. In addition, a mixed lymphocyte reaction assay indicated that ESC-NS/PCs modulated the allogeneic immune rejection. Taken together, our results indicate that allogeneic transplantation of ESC-NS/PCs from a nonhuman primate promoted functional recovery after SCI without tumorigenicity., Significance: This study demonstrates that allogeneic embryonic stem cell (ESC)-derived neural stem/progenitor cells (NS/PCs) promoted functional recovery after transplantation into the injured spinal cord in nonhuman primates. ESC-NS/PCs were chosen because ESC-NS/PCs are one of the controls for induced pluripotent stem cell-derived NS/PCs and because ESC derivatives are possible candidates for clinical use. This translational research using an allograft model of a nonhuman primate is critical for clinical application of grafting NS/PCs derived from various allogeneic pluripotent stem cells, especially induced pluripotent stem cells, into injured spinal cord at the subacute phase., (©AlphaMed Press.)

Purpose: To determine the imaging detail and diagnostic information that can be obtained at 7.0-T magnetic resonance (MR) imaging with a voxel volume of 9.5-14.0 nL as a means of evaluating the depth of mural invasion by gastric carcinomas ex vivo., Materials and Methods: This study was approved by the institutional review board, and written informed consent was obtained from each patient. Twenty gastric specimens containing 20 carcinomas were studied with a 7.0-T MR imaging system equipped with a four-channel surface coil. MR images were obtained with a 50-60 × 25-30 mm field of view, a 512 × 256 matrix, and a 1.0-mm section thickness, resulting in a voxel volume of 0.0095-0.0140 mm(3) (9.5-14.0 nL). The signal intensity of the gastric wall layers, tumor tissue, and fibrosis was described as low, intermediate, or high by comparing it with the signal intensity of the muscularis propria. Depth of invasion initially was assessed by two reviewers independently and then by the two reviewers in consensus. MR images were compared with histopathologic findings., Results: The 7.0-T T2-weighted MR images clearly depicted the normal gastric wall in all 20 specimens (100%) as consisting of seven layers, which clearly corresponded to the tissue layers of the gastric wall. These MR images enabled clear differentiation between tumor tissue and fibrosis. Reviewers disagreed on the depth of invasion at the initial reading in three (15%) of 20 specimens (between mucosa and submucosa in two specimens and between muscularis propria and subserosa and serosa in one specimen); however, in all 20 gastric carcinomas, the depth of invasion could be accurately determined on T2-weighted images after consensus interpretation., Conclusion: Ex vivo 7.0-T MR imaging enables clear delineation of the gastric wall layers and clear differentiation of tumor tissue from fibrosis and allows one to assess the depth of mural invasion by gastric carcinomas., (RSNA, 2015)

Purpose: To determine the usefulness of q-space MR imaging as means of evaluating the depth of mural invasion, the histologic grades, and lymph node metastasis in esophageal carcinomas., Methods: Twenty esophageal specimens each containing a carcinoma were studied with a 7.0 Tesla MR imaging system. q-Space MR images were obtained with a 50-60 mm × 25-30 mm field of view, 256 × 128 matrix, 2 mm section thickness, 10 b values ranging from 0 to 7163 s/mm(2) , and a motion-probing gradient in the y-direction, and the MR images were compared with the histopathologic findings., Results: The mean displacement maps, probability for zero displacement maps, and kurtosis maps in all 20 carcinomas (100%) made it possible to identify the depth of tumor invasion of the esophageal wall. These q-space MR imaging parameters were significantly correlated with the histologic grades of the esophageal carcinomas (P < 0.01), and also significantly correlated with their nuclear-cytoplasmic ratios (P < 0.01 or P < 0.001) and tumor cellularity (cell density) (P < 0.01 or P < 0.001). The q-space MR imaging parameters were also capable of differentiating between the metastatic lymph nodes and nonmetastatic lymph nodes (P < 0.01)., Conclusion: q-Space MR imaging ex vivo provides excellent diagnostic accuracy for evaluating mural invasion by esophageal carcinomas, the histologic grades of esophageal carcinomas, and lymph node metastasis by esophageal carcinomas., (© 2014 Wiley Periodicals, Inc.)

Purpose: To determine the usefulness of ultra-high-resolution magnetic resonance (MR) imaging at an ultra-high field strength (7.0T), using a voxel volume of 9.5-14nL, as means of evaluating the depth of mural invasion by esophageal carcinomas., Materials and Methods: Twenty esophageal specimens containing 20 carcinomas were studied using a 7.0-T MR imaging system with a four-channel surface coil. Ultra-high-resolution MR images were obtained with a field of view of 50-60mm×25-30mm, a matrix of 512×256, and a section thickness of 1.0mm, resulting in a voxel volume of 0.0095-0.014mm(3) (9.5-14nL). Differences between tumor tissue and the esophageal wall layers and between tumor tissue and fibrosis were evaluated using visual signal intensity scoring measurements. MR images were then compared with histopathologic findings as the reference standard., Results: Ultra-high-resolution T2-weighted MR images at 7.0T clearly depicted the normal esophageal wall in all 20 specimens (100%) as consisting of eight layers, which clearly corresponded to the tissue layers of the esophageal wall. Ultra-high-resolution T2-weighted MR images made it possible to differentiate between the tumor tissue and fibrosis clearly (P<0.01). In all 20 esophageal carcinomas (100%), ultra-high-resolution T2-weighted MR images made it possible to determine the depth of tumor invasion in the esophageal wall as observed in the histopathologic sections. Regional lymph node involvement was also clearly depicted in four specimens., Conclusion: Ultra-high-resolution 7.0-T MR imaging, using a voxel volume of 9.5-14nL, provides clear delineation of the esophageal wall layers, clear differentiation of tumor tissue from fibrosis, and excellent diagnostic accuracy for evaluating mural invasion by esophageal carcinomas., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To investigate the use of diffusion-tensor imaging (DTI) to detect denervation of the nigrostriatal pathway in a nonhuman primate model of Parkinson disease (PD) after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)., Materials and Methods: This study was approved by the institutional committee for animal experiments. DTI was performed in marmosets (n = 6) by using a 7-T magnetic resonance (MR) imager before and 10 weeks after administration of MPTP. Fixed brains of a normal marmoset and a marmoset model of PD (n = 1) were analyzed by using microscopic tractography. Tyrosine-hydroxylase staining of dopaminergic neurons and three-dimensional histologic analysis also were performed in normal marmosets (n = 2) and a PD marmoset model (n = 2) to validate the course of the nigrostriatal pathway revealed at tractography. Statistical analysis of voxel-based and post hoc region-of-interest analyses of DTI maps was performed by using a paired t test., Results: At voxel-based analysis of DTI before and after treatment, MPTP-treated marmoset brains showed significantly increased axial and radial diffusivity in the bilateral nigrostriatal pathway (P < .05, false discovery rate corrected). The largest area of significantly increased diffusivity was an area of axial diffusivity in the right hemispere (177 mm(3)) that corresponded to the location of dopaminergic neurodegeneration at histologic evaluation. Region-of-interest analysis revealed a 27% increase in axial diffusivity in the right hemisphere (1.198 mm(2)/sec ± 0.111 to 1.522 mm(2)/sec ± 0.118; P = .002). Three-dimensional histologic analysis with tyrosine-hydroxylase staining showed the course of the nigrostriatal pathway and degeneration in the PD marmoset model as the absence of a tyrosine-hydroxylase stained region. Microscopic tractography showed that the connection of the substantia nigra to the striatum followed the same course as the nigrostriatal pathway and fewer fiber tracts in the PD marmoset model., Conclusion: DTI and microscopic tractography showed the loss of fiber structures of the nigrostriatal pathway in the marmoset model of PD. The results of this study provide a potential basis for the use of DTI in the clinical diagnosis of PD., ((©) RSNA, 2015)

The dorsal and ventral hippocampal regions (dHP and vHP) are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP) and multi unit activities (MUA) upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2). Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD) fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP), which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS) were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

Purpose: To demonstrate the feasibility of diffusion-tensor magnetic resonance imaging (MRI) and tractography as a means of evaluating the individual layers of the normal esophageal wall by using esophageal specimens containing carcinoma., Materials and Methods: Twelve esophageal specimens each containing a carcinoma that were preserved in formalin were studied with a 7.0-T small-bore MR system equipped with a four-channel phased-array surface coil. Diffusion-tensor MR images were obtained with a field of view of 50-60 × 25-30 mm, matrix of 256 × 128, section thickness of 1 mm, b value of 1000 sec/mm(2) , and motion-probing gradient in seven noncollinear directions. The diffusion-weighted images, apparent diffusion coefficient (ADC) maps, fractional anisotropy (FA) maps, direction-encoded color FA maps, and tractographic images in the 12 esophageal specimens were compared with the histopathologic findings, which served as the gold standard., Results: The diffusion-weighted images, ADC maps, FA maps, and direction-encoded color FA maps depicted the normal esophageal wall in all 12 specimens (100%) as consisting of eight layers, which clearly corresponded to the tissue layers of the esophageal wall. The ADC, FA, λ1 , λ2 , and λ3 values of each layer of the normal esophageal wall were significantly different from the corresponding values of the adjacent layer or layers of the esophageal wall. Diffusion-tensor tractographic images were able to selectively display the layers of the normal esophageal wall., Conclusion: By looking at the normal part of esophageal specimens containing carcinoma, we have demonstrated that diffusion-tensor MRI and tractography are capable of depicting the individual tissue layers of the normal esophageal wall., (© 2013 Wiley Periodicals, Inc.)

Purpose: To determine the feasibility of diffusion-tensor magnetic resonance (MR) imaging and tractography as a means of evaluating the depth of mural invasion by esophageal carcinomas., Materials and Methods: This study was approved by the institutional review board, and written informed consent was obtained from each patient. Twenty esophageal specimens, each containing a carcinoma, were studied with a 7.0-T MR imaging system equipped with a four-channel phased-array surface coil. Diffusion-tensor MR images were obtained with a field of view of 50-60 mm × 25-30 mm, matrix of 256 × 128, section thickness of 1 mm, b value of 1000 sec/mm(2), and motion-probing gradient in seven noncollinear directions. The MR images were compared with the histopathologic findings as the reference standard. The differences in diffusion-tensor MR imaging parameters between the carcinoma and the layers of the esophageal wall were statistically analyzed by using the Dunnett test., Results: In all 20 carcinomas (100%), the diffusion-weighted images, apparent diffusion coefficient (ADC) maps, fractional anisotropy (FA) maps, λ1 maps, and direction-encoded color FA maps made it possible to determine the depth of tumor invasion of the esophageal wall that was observed during histopathologic examination. The λ1 maps showed the best contrast between the carcinomas and the layers of the esophageal wall. The carcinomas had both lower ADC values and lower FA values than the normal esophageal wall; thus, the carcinomas were clearly demarcated from the normal esophageal wall. Diffusion-tensor tractography images were also useful for determining the depth of tumor invasion of the esophageal wall., Conclusion: Diffusion-tensor MR imaging and tractography are feasible in esophageal specimens and provide excellent morphologic data for the evaluation of mural invasion by esophageal carcinomas., (© RSNA, 2014.)

Background: Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice., Methods: Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests., Results: Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals., Conclusions: We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM.

Naked mole-rats have a variety of distinctive features such as the organization of a hierarchical society (known as eusociality), extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI). Advanced MRI techniques such as diffusion tensor imaging (DTI), which generates high contrast images of fiber structures, can characterize unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D) images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualization of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

The aim of this study is to show the effects of estrogen upon its topical application on the wound healing process in young male mice. Fifty-six male mice aged 7 weeks old were divided into 4 groups: sham operation, castration, estrogen treatment after sham operation, and estrogen treatment after castration. Wound healing was observed daily until day 14 after wounding. Specimens were harvested on days 3, 7, 10, and 14, and stained to evaluate reepithelialization, inflammation, contraction, and collagenaccumulation. Wound healing periods of all groups were almost the same, although the concentration of serum estrogen in the estrogen-applied mice was very high, and that in the nonapplied groups was low. The numbers of macrophages in the castrated, estrogen-treated after sham operation, and estrogen-treated after castration groups were significantly decreased compared with that in the sham group in the inflammatory phase; however, the ratio of wound area in these groups did not decrease, and other histological data did not reveal any effects of estrogen. These results indicate that estrogen may show limited effectiveness for full-thickness cutaneous wound healing in young male mice, and decreased inflammation may not always be associated with decreased wound area. .

Diffusion-weighted magnetic resonance imaging provides detailed information about biological structures. In particular, diffusion tensor imaging and diffusion tensor tractography (DTT) are powerful tools for evaluating white matter fibers in the central nervous system. We previously established a reproducible spinal cord injury model in adult common marmosets and showed that DTT could be used to trace the neural tracts in the intact and injured spinal cord of these animals in vivo. Recently, many reports using DTT to analyze the spinal cord area have been published. Based on the findings from our experimental studies, we are now routinely performing DTT of the human spinal cord in the clinic. In this review we outline the basic principles of DTT, and describe the characteristics, limitations, and future uses of DTT to examine the spinal cord., (Copyright © 2012. Published by Elsevier Inc.)