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Phytochemical investigation on the rhizomes and roots of Gentiana scabra (Gentianaceae) led to the isolation of five new triterpenoids (1-5), together with seven known ones (6-12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data interpretation, ECD calculation and X-ray crystallographic analysis. Noticeably, compound 4 was an uncommon 3,4-seco-pentacyclic triterpenoid in natural products. The in vitro cytotoxic activities of all isolates against human cancer cell lines (HepG2, Hep3B, HCT116, and U87) were measured using MTT assay. Among them, compounds 2-9, 11, and 12 exhibited anti-proliferative effects against these tumor cell lines., (Copyright © 2024. Published by Elsevier B.V.)

Seven undescribed benzoate glycosides (1-7) and five known ones (8-12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 μM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Vision in humans and other primates enlists parallel processing streams in the dorsal and ventral visual cortex, known to support spatial and object processing, respectively. These streams are bridged, however, by a prominent white matter tract, the vertical occipital fasciculus (VOF), identified in both classical neuroanatomy and recent diffusion-weighted magnetic resonance imaging (dMRI) studies. Understanding the evolution of the VOF may shed light on its origin, function, and role in visually guided behaviors. To this end, we acquired high-resolution dMRI data from the brains of select mammalian species, including anthropoid and strepsirrhine primates, a tree shrew, rodents, and carnivores. In each species, we attempted to delineate the VOF after first locating the optic radiations in the occipital white matter. In all primate species examined, the optic radiation was flanked laterally by a prominent and coherent white matter fasciculus recognizable as the VOF. By contrast, the equivalent analysis applied to four non-primate species from the same superorder as primates (tree shrew, ground squirrel, paca, and rat) failed to reveal white matter tracts in the equivalent location. Clear evidence for a VOF was also absent in two larger carnivore species (ferret and fox). Although we cannot rule out the existence of minor or differently organized homologous fiber pathways in the non-primate species, the results suggest that the VOF has greatly expanded, or possibly emerged, in the primate lineage. This adaptation likely facilitated the evolution of unique visually guided behaviors in primates, with direct impacts on manual object manipulation, social interactions, and arboreal locomotion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The variations in cellular composition and tissue architecture measured with histology provide the biological basis for partitioning the brain into distinct cytoarchitectonic areas and for characterizing neuropathological tissue alterations. Clearly, there is an urgent need to develop whole-brain neuroradiological methods that can assess cortical cyto- and myeloarchitectonic features non-invasively. Mean apparent propagator (MAP) MRI is a clinically feasible diffusion MRI method that quantifies efficiently and comprehensively the net microscopic displacements of water molecules diffusing in tissues. We investigate the sensitivity of high-resolution MAP-MRI to detecting areal and laminar variations in cortical cytoarchitecture and compare our results with observations from corresponding histological sections in the entire brain of a rhesus macaque monkey. High-resolution images of MAP-derived parameters, in particular the propagator anisotropy (PA), non-gaussianity (NG), and the return-to-axis probability (RTAP) reveal cortical area-specific lamination patterns in good agreement with the corresponding histological stained sections. In a few regions, the MAP parameters provide superior contrast to the five histological stains used in this study, delineating more clearly boundaries and transition regions between cortical areas and laminar substructures. Throughout the cortex, various MAP parameters can be used to delineate transition regions between specific cortical areas observed with histology and to refine areal boundaries estimated using atlas registration-based cortical parcellation. Using surface-based analysis of MAP parameters we quantify the cortical depth dependence of diffusion propagators in multiple regions-of-interest in a consistent and rigorous manner that is largely independent of the cortical folding geometry. The ability to assess cortical cytoarchitectonic features efficiently and non-invasively, its clinical feasibility, and translatability make high-resolution MAP-MRI a promising 3D imaging tool for studying whole-brain cortical organization, characterizing abnormal cortical development, improving early diagnosis of neurodegenerative diseases, identifying targets for biopsies, and complementing neuropathological investigations., (Copyright © 2022. Published by Elsevier Inc.)

Diffusion magnetic resonance imaging (dMRI) is commonly used to assess the tissue and cellular substructure of the human brain. In the white matter, myelinated axons are the principal neural elements that shape dMRI through the restriction of water diffusion; however, in the gray matter the relative contributions of myelinated axons and other tissue features to dMRI are poorly understood. Here we investigate the determinants of diffusion in the cerebral cortex. Specifically, we ask whether myelinated axons significantly shape dMRI fractional anisotropy (dMRI-FA), a measure commonly used to characterize tissue properties in humans. We compared ultra-high resolution ex vivo dMRI data from the brain of a marmoset monkey with both myelin- and Nissl-stained histological sections obtained from the same brain after scanning. We found that the dMRI-FA did not match the spatial distribution of myelin in the gray matter. Instead dMRI-FA was more closely related to the anisotropy of stained tissue features, most prominently those revealed by Nissl staining and to a lesser extent those revealed by myelin staining. Our results suggest that unmyelinated neurites such as large caliber apical dendrites are the primary features shaping dMRI measures in the cerebral cortex., (© 2022. The Author(s).)

The brain is a highly organized, dynamic system whose network architecture is often assessed through resting functional magnetic resonance imaging (fMRI) functional connectivity. The functional interactions between brain areas, including those observed during rest, are assumed to stem from the collective influence of action potentials carried by long-range neural projections. However, the contribution of individual neurons to brain-wide functional connectivity has not been systematically assessed. Here we developed a method to concurrently measure and compare the spiking activity of local neurons with fMRI signals measured across the brain during rest. We recorded spontaneous activity from neural populations in cortical face patches in the macaque during fMRI scanning sessions. Individual cells exhibited prominent, bilateral coupling with fMRI fluctuations in a restricted set of cortical areas inside and outside the face patch network, partially matching the pattern of known anatomical projections. Within each face patch population, a subset of neurons was positively coupled with the face patch network and another was negatively coupled. The same cells showed inverse correlations with distinct subcortical structures, most notably the lateral geniculate nucleus and brainstem neuromodulatory centers. Corresponding connectivity maps derived from fMRI seeds and local field potentials differed from the single unit maps, particularly in subcortical areas. Together, the results demonstrate that the spiking fluctuations of neurons are selectively coupled with discrete brain regions, with the coupling governed in part by anatomical network connections and in part by indirect neuromodulatory pathways.

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T 1 -weighted images. We also derived subcortical template "SC21" from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats., (Copyright © 2021. Published by Elsevier Inc.)

Magnetic resonance imaging (MRI) is now an essential tool in the field of neuroscience involving non-human primates (NHP). Structural MRI scanning using T1-weighted (T1w) or T2-weighted (T2w) images provides anatomical information, particularly for experiments involving deep structures such as the basal ganglia and cerebellum. However, for certain subcortical structures, T1w and T2w image contrasts are insufficient for their detection of important anatomical details. To better visualize such structures in the macaque brain, we applied a relatively new method called quantitative susceptibility mapping (QSM), which enhances tissue contrast based on the local tissue magnetic susceptibility. The QSM significantly improved the visualization of important structures, including the ventral pallidum (VP), globus pallidus external and internal segments (GPe and GPi), substantia nigra (SN), subthalamic nucleus (STN) in the basal ganglia and the dentate nucleus (DN) in the cerebellum. We quantified this the contrast enhancement by systematically comparing of contrast-to-noise ratios (CNRs) of QSM images relative to the corresponding T1w and T2w images. In addition, QSM values of some structures were correlated to the age of the macaque subjects. These results identify the QSM method as a straightforward and useful tool for clearly visualizing details of subcortical structures that are invisible with more traditional scanning sequences., Competing Interests: Declaration of Competing Interest All authors claim that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Magnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared-RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm 3 voxel at 9.4 T. Test-retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.

Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechanisms leading to brain damage. This study aimed to characterize cortical lesions in marmosets with EAE using ultrahigh-field (7 T) MRI and histological analysis. Tissue preparation was optimized to enable the acquisition of high-spatial resolution (50-μm isotropic) T2*-weighted images. A total of 14 animals were scanned in this study, and 70% of the diseased animals presented at least one cortical lesion on postmortem imaging. Cortical lesions identified on MRI were verified with myelin proteolipid protein immunostaining. An optimized T2*-weighted sequence was developed for in vivo imaging and shown to capture 65% of cortical lesions detected postmortem. Immunostaining confirmed extensive demyelination with preserved neuronal somata in several cortical areas of EAE animals. Overall, this study demonstrates the relevance and feasibility of the marmoset EAE model to study cortical lesions, among the most important yet least understood features of MS., (Published by Oxford University Press 2020.)

Background: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact., Case Presentation: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother's family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother's family before they got back. His younger brother and one of his brother's children visited Wuhan on 5 January and came home on 6 January 2020., Conclusions: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.

The primate brain contains a large number of interconnected visual areas, whose spatial organization and intracortical projections show a high level of conservation across species. One fiber pathway of recent interest is the vertical occipital fasciculus (VOF), which is thought to support communication between dorsal and ventral visual areas in the occipital lobe. A recent comparative diffusion MRI (dMRI) study reported that the VOF in the macaque brain bears a similar topology to that of the human, running superficial and roughly perpendicular to the optic radiation. The present study reports a comparative investigation of the VOF in the common marmoset, a small New World monkey whose lissencephalic brain is approximately tenfold smaller than the macaque and 150-fold smaller than the human. High-resolution ex vivo dMRI of two marmoset brains revealed an occipital white matter structure that closely resembles that of the larger primate species, with one notable difference. Namely, unlike in the macaque and the human, the VOF in the marmoset is spatially fused with other, more anterior vertical tracts, extending anteriorly between the parietal and temporal cortices. We compare several aspects of this continuous structure, which we term the VOF complex (VOF +), and neighboring fasciculi to those of macaques and humans. We hypothesize that the essential topology of the VOF+ is a conserved feature of the posterior cortex in anthropoid primates, with a clearer fragmentation into multiple named fasciculi in larger, more gyrified brains.

While the fundamental importance of the white matter in supporting neuronal communication is well known, existing publications of primate brains do not feature a detailed description of its complex anatomy. The main barrier to achieving this is that existing primate neuroimaging data have insufficient spatial resolution to resolve white matter pathways fully. Here we present a resource that allows detailed descriptions of white matter structures and trajectories of fiber pathways in the marmoset brain. The resource includes: (1) the highest-resolution diffusion-weighted MRI data available to date, which reveal white matter features not previously described; (2) a comprehensive three-dimensional white matter atlas depicting fiber pathways that were either omitted or misidentified in previous atlases; and (3) comprehensive fiber pathway maps of cortical connections combining diffusion-weighted MRI tractography and neuronal tracing data. The resource, which can be downloaded from marmosetbrainmapping.org, will facilitate studies of brain connectivity and the development of tractography algorithms in the primate brain.

The default mode network (DMN) is associated with a wide range of brain functions. In humans, the DMN is marked by strong functional connectivity among three core regions: medial prefrontal cortex (mPFC), posterior parietal cortex (PPC), and the medial parietal and posterior cingulate cortex (PCC). Neuroimaging studies have shown that the DMN also exists in non-human primates, suggesting that it may be a conserved feature of the primate brain. Here, we found that, in common marmosets, the dorsolateral prefrontal cortex (dlPFC; peak at A8aD) has robust fMRI functional connectivity and reciprocal anatomical connections with the posterior DMN core regions (PPC and PCC), while the mPFC has weak connections with the posterior DMN core regions. This strong dlPFC but weak mPFC connectivity in marmoset differs markedly from the stereotypical DMN in humans. The mPFC may be involved in brain functions that are further developed in humans than in other primates.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the "National Institute of Mental Health Macaque Template", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies., (Copyright © 2017 ElsevierCompany. All rights reserved.)

The common marmoset (Callithrix jacchus) is a New-World monkey of growing interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool to unveil the anatomical and functional organization of the marmoset brain. To facilitate identification of regions of interest, it is desirable to register MR images to an atlas of the brain. However, currently available atlases of the marmoset brain are mainly based on 2D histological data, which are difficult to apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1-like contrast), T2w images, and multi-shell diffusion MRI. Based on the multi-modal MRI images, we manually delineated 54 cortical areas and 16 subcortical regions on one hemisphere of the brain (the core version). The 54 cortical areas were merged into 13 larger cortical regions according to their locations to yield a coarse version of the atlas, and also parcellated into 106 sub-regions using a connectivity-based parcellation method to produce a refined atlas. Finally, we compared the new atlas set with existing histology atlases and demonstrated its applications in connectome studies, and in resting state and stimulus-based fMRI. The atlas set has been integrated into the widely-distributed neuroimaging data analysis software AFNI and SUMA, providing a readily usable multi-modal template space with multi-level anatomical labels (including labels from the Paxinos atlas) that can facilitate various neuroimaging studies of marmosets., (Published by Elsevier Inc.)

Patterns of spontaneous brain activity, typically measured in humans at rest with fMRI, are used routinely to assess the brain's functional organization. The mechanisms that generate and coordinate the underlying neural fluctuations are largely unknown. Here we investigate the hypothesis that the nucleus basalis of Meynert (NBM), the principal source of widespread cholinergic and GABAergic projections to the cortex, contributes critically to such activity. We reversibly inactivated two distinct sites of the NBM in macaques while measuring fMRI activity across the brain. We found that inactivation led to strong, regionalized suppression of shared or "global" signal components of cortical fluctuations ipsilateral to the injection. At the same time, the commonly studied resting-state networks retained their spatial structure under this suppression. The results indicate that the NBM contributes selectively to the global component of functional connectivity but plays little if any role in the specific correlations that define resting-state networks., (Published by Elsevier Inc.)

Cortical activity during periods of rest is punctuated by widespread, synchronous events in both electrophysiological and hemodynamic signals, but their behavioral relevance remains unclear. Here we report that these events correspond to momentary drops in cortical arousal and are associated with activity changes in the basal forebrain and thalamus. Combining fMRI and electrophysiology in macaques, we first establish that fMRI transients co-occur with spectral shifts in local field potentials (LFPs) toward low frequencies. Applying this knowledge to fMRI data from the human connectome project, we find that the fMRI transients are strongest in sensory cortices. Surprisingly, the positive cortical transients occur together with negative transients in focal subcortical areas known to be involved with arousal regulation, most notably the basal forebrain. This subcortical involvement, combined with the prototypical pattern of LFP spectral shifts, suggests that commonly observed widespread variations in fMRI cortical activity are associated with momentary drops in arousal.

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and K ATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the K ATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

We present a new 3D template atlas of the anatomical subdivisions of the macaque brain, which is based on and aligned to the magnetic resonance imaging (MRI) data set and histological sections of the Saleem and Logothetis atlas. We describe the creation and validation of the atlas that, when registered with macaque structural or functional MRI scans, provides a straightforward means to estimate the boundaries between architectonic areas, either in a 3D volume with different planes of sections, or on an inflated brain surface (cortical flat map). As such, this new template atlas is intended for use as a reference standard for macaque brain research. Atlases and templates are available as both volumes and surfaces in standard NIFTI and GIFTI formats., (Published by Oxford University Press 2016.)

Aim: To investigate alterations in the fecal microbiome using 16S rRNA amplicon sequencing in couples in the same cohabitation environment., Methods: Fecal samples were collected from eight ulcerative colitis (UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16S rRNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units (OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sum test (R v3.1.2) was used to compare inter-individual differences. Differences with a P value < 0.05 were considered statistically significant., Results: Fecal microbial communities were more similar among UC patients than their healthy partners ( P = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the Firmicutes , especially Blautia , Clostridium , Coprococcus and Roseburia ( P < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included Akkermansiam , Bacteroides , Escherichia , Lactobacillales , Klebsiella and Parabacteroides . The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners., Conclusion: Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflicts of interest exist.

We compare several major white-matter tracts in human and macaque occipital lobe using diffusion magnetic resonance imaging. The comparison suggests similarities but also significant differences in the tracts. There are several apparently homologous tracts in the 2 species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. We could identify the macaque VOF (mVOF), which has been little studied. Its position is consistent with classical invasive anatomical studies by Wernicke. VOF homology is supported by similarity of the endpoints in V3A and ventral V4 across species. The mVOF fibers intertwine with the dorsal segment of the ILF, but the human VOF appears to be lateral to the ILF. These similarities and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Changes in brain activity accompanying shifts in vigilance and arousal can interfere with the study of other intrinsic and task-evoked characteristics of brain function. However, the difficulty of tracking and modeling the arousal state during functional MRI (fMRI) typically precludes the assessment of arousal-dependent influences on fMRI signals. Here we combine fMRI, electrophysiology, and the monitoring of eyelid behavior to demonstrate an approach for tracking continuous variations in arousal level from fMRI data. We first characterize the spatial distribution of fMRI signal fluctuations that track a measure of behavioral arousal; taking this pattern as a template, and using the local field potential as a simultaneous and independent measure of cortical activity, we observe that the time-varying expression level of this template in fMRI data provides a close approximation of electrophysiological arousal. We discuss the potential benefit of these findings for increasing the sensitivity of fMRI as a cognitive and clinical biomarker.

In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure-function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.

Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.

Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by (1)H, (13)C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure-activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons; however, its crucial mechanism of the metabolic changes of neurotransmitters remains ambiguous. The pathological mechanism of PD might involve cerebral metabolism perturbations. In this study, ex vivo proton nuclear magnetic resonance ((1)H NMR) was used to determine the level changes of 13 metabolites in the bilateral striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats. The results showed that, in the right striatum of 6-OHDA-induced PD rats, increased levels of glutamate (Glu) and γ-aminobutyric acid (GABA) concomitantly with decreased level of glutamine (Gln) were observed compared to the control. Whereas, in the left striatum of 6-OHDA-induced PD rats, increased level of Glu with decreased level of GABA and unchanged Gln were observed. Other cerebral metabolites including lactate, alanine, creatine, succinate, taurine, and glycine were also found to have some perturbations. The observed metabolic changes for Glu, Gln, and GABA are mostly likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle between astrocytes and neurons. The altered Gln and GABA levels are most likely as a strategy to protect neurons from Glu excitotoxic injury after striatal dopamine depletion. Changes in energy metabolism and tricarboxylic acid cycle might be involved in the pathogenesis of PD.

Injury to the primary visual cortex (V1) leads to the loss of visual experience. Nonetheless, careful testing shows that certain visually guided behaviours can persist even in the absence of visual awareness. The neural circuits supporting this phenomenon, which is often termed blindsight, remain uncertain. Here we demonstrate that the thalamic lateral geniculate nucleus (LGN) has a causal role in V1-independent processing of visual information. By comparing functional magnetic resonance imaging (fMRI) and behavioural measures with and without temporary LGN inactivation, we assessed the contribution of the LGN to visual functions of macaque monkeys (Macaca mulatta) with chronic V1 lesions. Before LGN inactivation, high-contrast stimuli presented to the lesion-affected visual field (scotoma) produced significant V1-independent fMRI activation in the extrastriate cortical areas V2, V3, V4, V5/middle temporal (MT), fundus of the superior temporal sulcus (FST) and lateral intraparietal area (LIP) and the animals correctly located the stimuli in a detection task. However, following reversible inactivation of the LGN in the V1-lesioned hemisphere, fMRI responses and behavioural detection were abolished. These results demonstrate that direct LGN projections to the extrastriate cortex have a critical functional contribution to blindsight. They suggest a viable pathway to mediate fast detection during normal vision.

Functional MRI (fMRI) has uncovered widespread hemodynamic fluctuations in the brain during rest. Recent electroencephalographic work in humans and microelectrode recordings in anesthetized monkeys have shown this activity to be correlated with slow changes in neural activity. Here we report that the spontaneous fluctuations in the local field potential (LFP) measured from a single cortical site in monkeys at rest exhibit widespread, positive correlations with fMRI signals over nearly the entire cerebral cortex. This correlation was especially consistent in a band of upper gamma-range frequencies (40-80 Hz), for which the hemodynamic signal lagged the neural signal by 6-8 s. A strong, positive correlation was also observed in a band of lower frequencies (2-15 Hz), albeit with a lag closer to zero. The global pattern of correlation with spontaneous fMRI fluctuations was similar whether the LFP signal was measured in occipital, parietal, or frontal electrodes. This coupling was, however, dependent on the monkey's behavioral state, being stronger and anticipatory when the animals' eyes were closed. These results indicate that the often discarded global component of fMRI fluctuations measured during the resting state is tightly coupled with underlying neural activity.

The monkey's auditory cortex includes a core region on the supratemporal plane (STP) made up of the tonotopically organized areas A1, R, and RT, together with a surrounding belt and a lateral parabelt region. The functional studies that yielded the tonotopic maps and corroborated the anatomical division into core, belt, and parabelt typically used low-amplitude pure tones that were often restricted to threshold-level intensities. Here we used functional magnetic resonance imaging in awake rhesus monkeys to determine whether, and if so how, the tonotopic maps and the pattern of activation in core, belt, and parabelt are affected by systematic changes in sound intensity. Blood oxygenation level-dependent (BOLD) responses to groups of low- and high-frequency pure tones 3-4 octaves apart were measured at multiple sound intensity levels. The results revealed tonotopic maps in the auditory core that reversed at the putative areal boundaries between A1 and R and between R and RT. Although these reversals of the tonotopic representations were present at all intensity levels, the lateral spread of activation depended on sound amplitude, with increasing recruitment of the adjacent belt areas as the intensities increased. Tonotopic organization along the STP was also evident in frequency-specific deactivation (i.e. "negative BOLD"), an effect that was intensity-specific as well. Regions of positive and negative BOLD were spatially interleaved, possibly reflecting lateral inhibition of high-frequency areas during activation of adjacent low-frequency areas, and vice versa. These results, which demonstrate the strong influence of tonal amplitude on activation levels, identify sound intensity as an important adjunct parameter for mapping the functional architecture of auditory cortex.

The role of primary visual cortex (V1) in determining the contents of perception is controversial. Human functional magnetic resonance imaging (fMRI) studies of perceptual suppression have revealed a robust drop in V1 activity when a stimulus is subjectively invisible. In contrast, monkey single-unit recordings have failed to demonstrate such perception-locked changes in V1. To investigate the basis of this discrepancy, we measured both the blood oxygen level-dependent (BOLD) response and several electrophysiological signals in two behaving monkeys. We found that all signals were in good agreement during conventional stimulus presentation, showing strong visual modulation to presentation and removal of a stimulus. During perceptual suppression, however, only the BOLD response and the low-frequency local field potential (LFP) power showed decreases, whereas the spiking and high-frequency LFP power were unaffected. These results demonstrate that the coupling between the BOLD and electrophysiological signals in V1 is context dependent, with a marked dissociation occurring during perceptual suppression.

Echo-planar imaging (EPI) is vulnerable to geometric distortion and N/2 ghosting. These artifacts can be analyzed with an intuitive k-t space tool, and here we propose a simple method for their correction. In a slightly modified additional EPI acquisition, we sample the k-t space with a shift in k(y) by adding a small area to the phase-encoding (PE) gradient. Physically, the added gradient area creates a relative phase ramp across the object and directly encodes the undistorted original y-coordinate of each voxel into a phase difference between two distorted complex images, in a method called "phase labeling for additional coordinate encoding" (PLACE). The phase information is then used to map the mismapped signals back to their original locations for geometric and intensity correction. Smoothing of expanded complex data matrix effectively reduces noise in the differential phase map and allows subpixel warping. The two acquired images can also be averaged to effectively suppress the N/2 ghost. Efficient correction for both artifacts can be achieved with three acquisitions. These acquisitions can also serve as reference scans to correct for geometric distortion and/or N/2 ghost artifacts on all images in a time series. The technique was successfully demonstrated in phantom and animal studies.

Like cerebral blood flow (CBF), cerebral blood volume (CBV) is an important physiological parameter closely associated with brain activity and thus, noninvasive quantification of CBV during brain activation provides another opportunity to investigate the relationship between neuronal activity and hemodynamic changes. In this paper, a new method is presented that is able to quantify CBV at rest and during activation. Specifically, using an inversion recovery pulse sequence, a set of brain images was collected at various inversion times (TIs). At each TI, functional images were acquired with a block-design visual stimulation paradigm. A biophysical model comprised of multiple tissue components was developed and was utilized for the determination of CBV using the visual stimulation data. MRI experiments on five healthy volunteers showed that CBV was 5.0 +/- 1.5 ml blood/100 ml brain during rest and increased to 6.6 +/- 1.8 ml blood/100 ml brain following visual stimulation. Furthermore, experiments with visual stimulation at two frequencies (2 and 8 Hz) showed that the increases in CBV correlated with the strength of stimulation. This technique, with its ability to measure quantitative CBV values noninvasively, provides a valuable tool for quantifying hemodynamic signals associated with brain activation.

Overt speech production in functional magnetic resonance imaging (fMRI) studies is often associated with imaging artifacts, attributable to both movement and susceptibility. Various image-processing methods have been proposed to remove these artifacts from the data but none of these methods has been shown to work with continuous overt speech, at least over periods greater than 3 s. In this study natural, continuous, overt sentence production was evaluated in normal volunteers using both arterial spin labeling (ASL) and conventional echoplanar blood oxygenation level-dependent (BOLD) imaging sequences on the same 1.5-T scanner. We found a high congruency between activation results obtained with ASL and the de facto gold standard in overt language production imaging, positron emission tomography (PET). No task-related artifacts were found in the ASL study. However, the BOLD data showed artifacts that appeared as large bilateral false-positive temporopolar activations; percent signal change estimated in these regions showed signal increases and temporal dynamics that were incongruent with typical BOLD activations. These artifacts were not distributed uniformly, but were aligned at the frontotemporal base, close to the oropharynx. The calculated head movement parameters for overt speech blocks were within the range of the rest blocks, indicating that head movement is unlikely the reason for the artifact. We conclude that ASL is not influenced by overt speech artifacts, whereas BOLD showed significant susceptibility artifacts, especially in the opercular and insular regions, where activation would be expected. ASL may prove to be the method of choice for fMRI investigations of continuous overt speech.

Attenuating the static signal in arterial spin tagging (ASSIST) was initially developed for 3D imaging of cerebral blood flow. To enable the simultaneous collection of cerebral blood flow and BOLD data, a multi-slice version of ASSIST is proposed. As with the 3D version, this sequence uses multiple inversion pulses during the tagging period to suppress the static signal. To maintain background suppression in all slices, the multi-slice sequence applies additional inversion pulses between slice acquisitions. The utility of the sequence was demonstrated by simultaneously acquiring ASSIST and BOLD data during a functional task and by collecting resting-state ASSIST data over a large number of slices. In addition, the temporal stability of the perfusion signal was found to be 60% greater at 3 T compared to 1.5 T, which was attributed to the insensitivity of ASSIST to physiologic noise., ((c) 2005 Wiley-Liss, Inc.)

Aim: To study the synthesis and antibacterial activity of ciprofloxacin derivatives., Methods: Ciprofloxacin derivatives were synthesized primarily from 2-methyl-5-nitroimidazol and ciprofloxacin through nucleophilic substitution. The antibacterial activity of the synthesized compounds were tested., Results: Nine new compounds were synthesized. The structure of the title compounds were confirmed by 1H NMR, MS and element analysis., Conclusion: Compounds II, IVC and IVD showed appreciable antibacterial activity, and were worth further studying.

A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.

The work presented here uses combined blood oxygenation level-dependent (BOLD) and arterial spin tagging (AST) approaches to study the effect of indomethacin on cerebral blood flow (CBF) and oxygen consumption (CMRO(2)) increases during motor activation. While indomethacin reduced the CBF increase during activation, it did not significantly affect the CMRO(2) increase during activation. The ratio of the activation-induced CBF increase in the presence and absence of indomethacin was 0.54 +/- 0.08 (+/-SEM, n = 8, P < 0.001), while the ratio of the CMRO(2) increase in the presence and absence of the drug was 1.02 +/- 0.08 (+/-SEM, N = 8, ns). Potential difficulties in estimating CMRO(2) changes from combined BOLD/AST data are discussed.

Aim: To study the synthesis and antibacterial activity of pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol., Methods: Pyridonecarboxylic acid derivatives containing 2-methyl-5-nitroimidazol were synthesized primarily from 2-methyl-5-nitroimidazol, norfloxacin, ciprofloxacin, enoxacin via nucleophilic substitution and esterification. The antibacterial activity of the nine target compounds were tested., Results: Nine new compounds were synthesized (IIa-c and IIIa-f). The structure of the title compounds were identified by 1HNMR, MS as well as elementary analysis., Conclusion: Compounds IIa, IIb and IIc showed antibacterial activity, and were worth further studying.

Purpose: To investigate using an arterial spin tagging (AST) approach the effect of indomethacin on the cerebral blood flow (CBF) response to hypercapnia., Materials and Methods: Subjects inhaled a gas mixture containing 6% CO(2) for two 5-minute periods, which were separated by a 10-minute interval, in which subjects inhaled room air. In six subjects, indomethacin (i.v., 0.2 mg/kg) was infused in the normocapnic interval between the two hypercapnic periods., Results: Indomethacin reduced normocapnic gray matter CBF by 36 +/- 5% and reduced the CBF increase during hypercapnia from 43 +/- 9% to 16 +/- 5% in gray matter (P < 0.001) and from 48 +/- 11% to 35 +/- 9% in white matter (P < 0.025)., Conclusion: The results demonstrate that an AST approach can measure the effects of indomethacin on global CBF increases during hypercapnia and suggest that an AST approach could be used to investigate pharmacological effects on focal CBF increases during functional activation., (Published 2002 Wiley-Liss, Inc.)

We present a method of manipulative reduction, immobilisation and fixation using a U-shaped plaster with the elbow in extension for extension-type supracondylar fractures of the humerus in children. When the elbow is in full extension, both the extensor and the flexor muscles are neutralised during manipulative reduction and the carrying angle can be easily assessed thus preventing cubitus varus, the most common complication. In order to evaluate the efficiency of this method, we compared the clinical results of the new method with those of conventional treatment. In a group of 95 children who sustained an extension-type supracondylar fracture of the humerus, 49 were treated by the new method and 46 by the conventional method, reduction and immobilisation in a plaster slab with the elbow in flexion. Reduction and immobilisation were easily achieved and reliably maintained by one manipulation for all the children treated by the new method. In 12 children treated by the conventional method, the initial reduction failed and in seven secondary displacement of the distal fragment occurred during the period of immobilisation in plaster. All required a second or third manipulation. Of the 46 children, 28 (60.9%) had developed cubitus varus at a mean follow-up of 4.6 years when treated by the conventional method. None of the children treated by the new method developed cubitus varus. The mean score, according to the Hospital for Special Surgery (HSS) elbow scoring system, was 91 points using the new method and 78 with the conventional method. The results were statistically significant with regard to the incidence of cubitus varus and the elbow score (p < 0.01) suggesting that the new method is reliable and gives a satisfactory outcome.

Steady-state arterial spin tagging approaches can provide quantitative images of CBF, but have not been validated in humans. The work presented here compared CBF values measured using steady-state arterial spin tagging with CBF values measured in the same group of human subjects using the H(2)(15)O IV bolus PET method. Blood flow values determined by H(2)(15)O PET were corrected for the known effects of incomplete extraction of water across the blood brain barrier. For a cortical strip ROI, blood flow values determined using arterial spin tagging (64+/-12 cc/100 g/min) were not statistically different from corrected blood flow values determined using H(2)(15)O PET (67+/-13 cc/100 g/min). However, for a central white matter ROI, blood flow values determined using arterial spin tagging were significantly underestimated compared to corrected blood flow values determined using H(2)(15)O PET. This underestimation could be caused by an underestimation of the arterial transit time for white matter regions.

Phase-encoded multishot SPIRAL approaches were used to acquire true 3D cerebral blood flow images of the human head using arterial spin tagging approaches. Multiple-inversion background suppression techniques, which suppress phase noise due to interacquisition fluctuations in the static magnetic field, reduced the temporal standard deviation of true 3D delta M images acquired using arterial spin tagging approaches by approximately 50%. Background suppressed arterial spin tagging (ASSIST) approaches were used to obtain high-resolution isotropic true 3D cerebral blood flow images, and to obtain true 3D activation images during cognitive (working memory) tasks. Magn Reson Med 44:92-100, 2000. Published 2000 Wiley-Liss, Inc.

Steady-state arterial spin tagging approaches were used to construct multislice images of relative cerebral blood flow changes during finger-tapping tasks. Statistically significant increases in cerebral blood flow were observed in primary sensorimotor cortex in all seven subjects. The mean volume of the activated region in the contralateral primary sensorimotor cortex was 0.9 cm(3), and the mean increase in cerebral blood flow in the activated area was 54% +/- 11%. Although the extended spatial coverage is advantageous for activation studies, the intrinsic sensitivity of the multislice approach is smaller than the intrinsic sensitivity of the single-slice, arterial spin tagging approach. Magn Reson Med 42:404-407, 1999. Published 1999 Wiley-Liss, Inc.

Low frequency drift (0.0-0.015 Hz) has often been reported in time series fMRI data. This drift has often been attributed to physiological noise or subject motion, but no studies have been done to test this assumption. Time series T*2-weighted volumes were acquired on two clinical 1.5 T MRI systems using spiral and EPI readout gradients from cadavers, a normal volunteer, and nonhomogeneous and homogeneous phantoms. The data were tested for significant differences (P = 0.001) from Gaussian noise in the frequency range 0.0-0.015 Hz. The percentage of voxels that were significant in data from the cadaver, normal volunteer, nonhomogeneous and homogeneous phantoms were 13.7-49.0%, 22.1-61.9%, 46.4-68.0%, and 1.10%, respectively. Low frequency drift was more pronounced in regions with high spatial intensity gradients. Significant drifting was present in data acquired from cadavers and nonhomogeneous phantoms and all pulse sequences tested, implying that scanner instabilities and not motion or physiological noise may be the major cause of the drift., (Copyright 1999 Academic Press.)

Steady-state arterial spin-tagging MRI approaches were used to quantitate regional cerebral blood flow increases in prefrontal cortex during a working memory ("two-back") task in six normal subjects. Statistically significant increases in cerebral blood flow in prefrontal cortex were observed in all six subjects: the average increase in cerebral blood flow in activated prefrontal cortex regions was 22 +/- 5 cc/100 g/min (23 +/- 7%). The results demonstrate that spin-tagging approaches can be used to follow focal activation in prefrontal cortex during cognitive tasks.