Comparison of Multivendor Single-Voxel MR Spectroscopy Data Acquired in Healthy Brain at 26 Sites.

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article.

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites.

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Resting state cerebral blood flow with arterial spin labeling MRI in developing human brains.

The development of brain circuits is coupled with changes in neurovascular coupling, which refers to the close relationship between neural activity and cerebral blood flow (CBF). Studying the characteristics of CBF during resting state in developing brain can be a complementary way to understand the functional connectivity of the developing brain. Arterial spin labeling (ASL), as a noninvasive MR technique, is particularly attractive for studying cerebral perfusion in children and even newborns. We have collected pulsed ASL data in resting state for 47 healthy subjects from young children to adolescence (aged from 6 to 20 years old). In addition to studying the developmental change of static CBF maps during resting state, we also analyzed the CBF time series to reveal the dynamic characteristics of CBF in differing age groups. We used the seed-based correlation analysis to examine the temporal relationship of CBF time series between the selected ROIs and other brain regions. We have shown the developmental patterns in both static CBF maps and dynamic characteristics of CBF. While higher CBF of default mode network (DMN) in all age groups supports that DMN is the prominent active network during the resting state, the CBF connectivity patterns of some typical resting state networks show distinct patterns of metabolic activity during the resting state in the developing brains.

Big GABA: Edited MR spectroscopy at 24 research sites.

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.

Morphological features of the neonatal brain following exposure to regional anesthesia during labor and delivery.

INTRODUCTION: Recent animal and human epidemiological studies suggest that early childhood exposure to anesthesia may have adverse effects on brain development. As more than 50% of pregnant women in the United States and one-third in the United Kingdom receive regional anesthesia during labor and delivery, understanding the effects of perinatal anesthesia on postnatal brain development has important public health relevance. METHODS: We used high-resolution magnetic resonance imaging (MRI) to assess the effects of regional anesthesia during labor and delivery as part of a larger study of perinatal exposures on the morphological features of the neonatal brain. We mapped morphological features of the cortical surface in 37 healthy infants, 24 exposed and 13 unexposed to regional anesthesia at delivery, who were scanned within the first 6 weeks of life. RESULTS: Infants exposed to maternal anesthesia compared with unexposed infants had greater local volumes in portions of the frontal and occipital lobes bilaterally and right posterior portion of the cingulate gyrus. Longer durations of exposure to anesthesia correlated positively with local volumes in the occipital lobe. CONCLUSIONS: Anesthesia exposure during labor and delivery was associated with larger volumes in portions of the frontal and occipital lobes and cingulate gyrus in neonates. Longitudinal MRI studies are needed to determine whether these morphological effects of anesthesia persist and what their consequences on cognition and behavior may be.

Changes in corticostriatal connectivity during reinforcement learning in humans.

Many computational models assume that reinforcement learning relies on changes in synaptic efficacy between cortical regions representing stimuli and striatal regions involved in response selection, but this assumption has thus far lacked empirical support in humans. We recorded hemodynamic signals with fMRI while participants navigated a virtual maze to find hidden rewards. We fitted a reinforcement-learning algorithm to participants' choice behavior and evaluated the neural activity and the changes in functional connectivity related to trial-by-trial learning variables. Activity in the posterior putamen during choice periods increased progressively during learning. Furthermore, the functional connections between the sensorimotor cortex and the posterior putamen strengthened progressively as participants learned the task. These changes in corticostriatal connectivity differentiated participants who learned the task from those who did not. These findings provide a direct link between changes in corticostriatal connectivity and learning, thereby supporting a central assumption common to several computational models of reinforcement learning.

Improving the spectral resolution and spectral fitting of (1) H MRSI data from human calf muscle by the SPREAD technique.

Proton magnetic resonance spectroscopic imaging ((1) H MRSI) has been used for the in vivo measurement of intramyocellular lipids (IMCLs) in human calf muscle for almost two decades, but the low spectral resolution between extramyocellular lipids (EMCLs) and IMCLs, partially caused by the magnetic field inhomogeneity, has hindered the accuracy of spectral fitting. The purpose of this paper was to enhance the spectral resolution of (1) H MRSI data from human calf muscle using the SPREAD (spectral resolution amelioration by deconvolution) technique and to assess the influence of improved spectral resolution on the accuracy of spectral fitting and on in vivo measurement of IMCLs. We acquired MRI and (1) H MRSI data from calf muscles of three healthy volunteers. We reconstructed spectral lineshapes of the (1) H MRSI data based on field maps and used the lineshapes to deconvolve the measured MRS spectra, thereby eliminating the line broadening caused by field inhomogeneities and improving the spectral resolution of the (1) H MRSI data. We employed Monte Carlo (MC) simulations with 200 noise realizations to measure the variations of spectral fitting parameters and used an F-test to evaluate the significance of the differences of the variations between the spectra before SPREAD and after SPREAD. We also used Cramer-Rao lower bounds (CRLBs) to assess the improvements of spectral fitting after SPREAD. The use of SPREAD enhanced the separation between EMCL and IMCL peaks in (1) H MRSI spectra from human calf muscle. MC simulations and F-tests showed that the use of SPREAD significantly reduced the standard deviations of the estimated IMCL peak areas (p < 10(-8) ), and the CRLBs were strongly reduced (by ~37%).

Automated assessment of the quality of diffusion tensor imaging data using color cast of color-encoded fractional anisotropy images.

Diffusion tensor imaging (DTI) data often suffer from artifacts caused by motion. These artifacts are especially severe in DTI data from infants, and implementing tight quality controls is therefore imperative for DTI studies of infants. Currently, routine procedures for quality assurance of DTI data involve the slice-wise visual inspection of color-encoded, fractional anisotropy (CFA) images. Such procedures often yield inconsistent results across different data sets, across different operators who are examining those data sets, and sometimes even across time when the same operator inspects the same data set on two different occasions. We propose a more consistent, reliable, and effective method to evaluate the quality of CFA images automatically using their color cast, which is calculated on the distribution statistics of the 2D histogram in the color space as defined by the International Commission on Illumination (CIE) on lightness and a and b (LAB) for the color-opponent dimensions (also known as the CIELAB color space) of the images. Experimental results using DTI data acquired from neonates verified that this proposed method is rapid and accurate. The method thus provides a new tool for real-time quality assurance for DTI data.

Neural correlates of reward-based spatial learning in persons with cocaine dependence.

Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.

Ultra-high-field MR imaging in multiple sclerosis.

In multiple sclerosis (MS), MRI is the most important paraclinical tool used to inform diagnosis and for monitoring disease evolution, either natural or modified by treatment. The increased availability of ultra-high-field magnets (7 Tesla or higher) gives rise to questions about the main benefits of and challenges for their use in patients with MS. The main advantages of ultra-high-field MRI are the improved signal-to-noise ratio, greater chemical shift dispersion, and improved contrast due to magnetic susceptibility variations, which lead to increased sensitivity to the heterogeneous pathological substrates of the disease. At present, ultra-high-field MRI is mainly used to improve our understanding of MS pathogenesis. This review discusses the main achievements that have so far come from the use of these scanners, which are: better visualisation of white matter lesions and their morphological characteristics; an improvement in the ability to visualise grey matter lesions and their exact location; the quantification of 'novel' metabolites which may have a role in axonal degeneration; and greater sensitivity to iron accumulation. The application of ultra-high-field systems in standard clinical practice is still some way off since their role in the diagnostic work-up of patients at presentation with clinically isolated syndromes, or in monitoring disease progression or treatment response in patients with definite MS, needs to be established. Additional challenges remain in the development of morphological, quantitative and functional imaging methods at these field strengths, techniques which may ultimately lead to novel biomarkers for monitoring disease evolution and treatment response.

Distinct neural circuits subserve interpersonal and non-interpersonal emotions.

Emotions elicited by interpersonal versus non-interpersonal experiences have different effects on neurobiological functioning in both animals and humans. However, the extent to which the brain circuits underlying interpersonal and non-interpersonal emotions are distinct still remains unclear. The goal of our study was to assess whether different neural circuits are implicated in the processing of arousal and valence of interpersonal versus non-interpersonal emotions. During functional magnetic resonance imaging, participants imagined themselves in emotion-eliciting interpersonal or non-interpersonal situations and then rated the arousal and valence of emotions they experienced. We identified (1) separate neural circuits that are implicated in the arousal and valence dimensions of interpersonal versus non-interpersonal emotions, (2) circuits that are implicated in arousal and valence for both types of emotion, and (3) circuits that are responsive to the type of emotion, regardless of the valence or arousal level of the emotion. We found extensive recruitment of limbic (for arousal) and temporal-parietal (for valence) systems associated with processing of specifically interpersonal emotions compared to non-interpersonal ones. The neural bases of interpersonal and non-interpersonal emotions may, therefore, be largely distinct.

Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia.

Schizophrenia is associated with extensive neurocognitive and behavioral impairments. Studies indicate that N-acetylaspartate (NAA), a marker of neuronal integrity, and choline, a marker of cell membrane turnover and white matter integrity, may be altered in schizophrenia. Davunetide is a neurotrophic peptide that can enhance cognitive function in animal models of neurodegeneration. Davunetide has recently demonstrated modest functional improvement in a study of people with schizophrenia. In a subset of these subjects, proton magnetic resonance spectroscopy ((1)H-MRS) was conducted to explore the effects of davunetide on change in NAA/creatine (NAA/Cr) and choline/creatine (choline/Cr) over 12 weeks of treatment. Of 63 outpatients with schizophrenia who received randomized davunetide (5 and 30 mg/day) or placebo in the parent clinical trial, 18 successfully completed (1)H-MRS in dorsolateral prefrontal cortex (DLPFC) at baseline and at 12 weeks. Cognition was assessed using the MATRICS Consensus Cognitive Battery (MCCB). NAA/Cr was unchanged for combined high- and low-dose davunetide groups (N=11). NAA/Cr in the high-dose davunetide group (N=8) suggested a trend increase of 8.0% (P=0.072) over placebo (N=7). Choline/Cr for combined high- and low-dose davunetide groups suggested a 6.4% increase (P=0.069), while the high-dose group showed a 7.9% increase (P=0.040) over placebo. Baseline NAA/Cr correlated with the composite MCCB score (R=0.52, P=0.033), as did individual cognitive domains of attention/vigilance, verbal learning, and social cognition; however, neither metabolite correlated with functional capacity. In this exploratory study, 12 weeks of adjunctive davunetide appeared to produce modest increases in NAA/Cr and choline/Cr in DLPFC in people with schizophrenia. This is consistent with a potential neuroprotective mechanism for davunetide. The data also support use of MRS as a useful biomarker of baseline cognitive function in schizophrenia. Future clinical and preclinical studies are needed to fully define the mechanism of action and cognitive effects of davunetide in schizophrenia.

Multimodal magnetic resonance imaging: The coordinated use of multiple, mutually informative probes to understand brain structure and function.

Differing imaging modalities provide unique channels of information to probe differing aspects of the brain's structural or functional organization. In combination, differing modalities provide complementary and mutually informative data about tissue organization that is more than their sum. We acquired and spatially coregistered data in four MRI modalities--anatomical MRI, functional MRI, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS)--from 20 healthy adults to understand how interindividual variability in measures from one modality account for variability in measures from other modalities at each voxel of the brain. We detected significant correlations of local volumes with the magnitude of functional activation, suggesting that underlying variation in local volumes contributes to individual variability in functional activation. We also detected significant inverse correlations of NAA (a putative measure of neuronal density and viability) with volumes of white matter in the frontal cortex, with DTI-based measures of tissue organization within the superior longitudinal fasciculus, and with the magnitude of functional activation and default-mode activity during simple visual and motor tasks, indicating that substantial variance in local volumes, white matter organization, and functional activation derives from an underlying variability in the number or density of neurons in those regions. Many of these imaging measures correlated with measures of intellectual ability within differing brain tissues and differing neural systems, demonstrating that the neural determinants of intellectual capacity involve numerous and disparate features of brain tissue organization, a conclusion that could be made with confidence only when imaging the same individuals with multiple MRI modalities.

Metabolite Mapping with Extended Brain Coverage Using a Fast Multisection MRSI Pulse Sequence and a Multichannel Coil.

Multisection magnetic resonance spectroscopic imaging is a widely used pulse sequence that has distinct advantages over other spectroscopic imaging sequences, such as dynamic shimming, large region-of-interest coverage within slices, and rapid data acquisition. It has limitations, however, in the number of slices that can be acquired in realistic scan times and information loss from spacing between slices. In this paper, we synergize the multi-section spectroscopic imaging pulse sequence with multichannel coil technology to overcome these limitations. These combined techniques now permit elimination of the gaps between slices and acquisition of a larger number of slices to realize the whole brain metabolite mapping without incurring the penalties of longer repetition times (and therefore longer acquisition times) or lower signal-to-noise ratios.

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play.

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12-42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers' may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation.

Convection-enhanced delivery of topotecan into a PDGF-driven model of glioblastoma prolongs survival and ablates both tumor-initiating cells and recruited glial progenitors.

The contribution of microenvironment to tumor growth has important implications for optimizing chemotherapeutic response and understanding the biology of recurrent tumors. In this study, we tested the effects of locally administered topotecan on a rat model of glioblastoma that is induced by intracerebral injection of PDGF (platelet-derived growth factor)-IRES (internal ribosome entry site)-GFP (green fluorescent protein)-expressing retrovirus, treated the tumors by convection-enhanced delivery (CED) of topotecan (136 µmol/L) for 1, 4, or 7 days, and then characterized the effects on both the retrovirus-transformed tumor cells (GFP(+) cells) as well as the uninfected glial progenitor cells (GFP(-) cells) that are recruited to the tumor. Topotecan treatment reduced GFP(+) cells about 10-fold and recruited progenitors by about 80-fold while providing a significant survival advantage that improved with greater treatment duration. Regions of glial progenitor ablation occurred corresponding to the anatomic distribution of topotecan as predicted by MRI of a surrogate tracer. Histopathologic changes in recurrent tumors point to a decrease in recruitment, most likely due to the chemotherapeutic ablation of the recruitable progenitor pool.

Neural systems subserving valence and arousal during the experience of induced emotions.

The circumplex model of affect construes all emotions as linear combinations of 2 independent neurophysiological dimensions, valence and arousal. We used functional magnetic resonance imaging to identify the neural networks subserving valence and arousal, and we assessed, in 10 participants, the associations of the BOLD (blood oxygen level-dependent) response, an indirect index of neural activity, with ratings of valence and arousal during the emotional experiences induced by the presentation of evocative sentences. Unpleasant emotional experience was associated with increased BOLD signal intensities in the supplementary motor, anterior midcingulate, right dorsolateral prefrontal, occipito-temporal, inferior parietal, and cerebellar cortices. Highly arousing emotions were associated with increased BOLD signal intensities in the left thalamus, globus pallidus, caudate, parahippocampal gyrus, amygdala, premotor cortex, and cerebellar vermis. Separate analyses using a finite impulse response model confirmed these results and revealed that pleasant emotions engaged an additional network that included the midbrain, ventral striatum, and caudate nucleus, all portions of a reward circuit. These findings suggest the existence of distinct networks subserving the valence and arousal dimensions of emotions, with midline and medial temporal lobe structures mediating arousal and dorsal cortical areas and mesolimbic pathways mediating valence.

A virtual reality-based FMRI study of reward-based spatial learning.

Although temporo-parietal cortices mediate spatial navigation in animals and humans, the neural correlates of reward-based spatial learning are less well known. Twenty-five healthy adults performed a virtual reality fMRI task that required learning to use extra-maze cues to navigate an 8-arm radial maze and find hidden rewards. Searching the maze in the spatial learning condition compared to the control conditions was associated with activation of temporo-parietal regions, albeit not including the hippocampus. The receipt of rewards was associated with activation of the hippocampus in a control condition when using the extra-maze cues for navigation was rendered impossible by randomizing the spatial location of cues. Our novel experimental design allowed us to assess the differential contributions of the hippocampus and other temporo-parietal areas to searching and reward processing during reward-based spatial learning. This translational research will permit parallel studies in animals and humans to establish the functional similarity of learning systems across species; cellular and molecular studies in animals may then inform the effects of manipulations on these systems in humans, and fMRI studies in humans may inform the interpretation and relevance of findings in animals.

Techniques for in utero, longitudinal MRI of fetal brain development in baboons at 3T.

Magnetic Resonance Imaging (MRI) is a promising tool for the noninvasive, longitudinal study of developing primate brains. We developed a protocol to scan pregnant baboons serially at 3T for up to 3h per session. This protocol includes procedures for animal preparation, anesthesia, MRI scanning, and post-scan animal care. We applied this protocol to scan 5 baboons multiple times across the latter 70% of gestation-from as early as 56 days post-conceptional age to as late as 185 days (term approximately 180 days). We successfully acquired high-resolution anatomical images and maps of relaxation times (T(1) and T(2)) of the fetal brains at multiple time points across gestation. These images and maps demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the convergence of contrast is a consequence of the continuous change in relaxation times during fetal brain development. We estimated the rates of decrease of T(1) and T(2) in white matter and gray matter, respectively. In addition, we measured the volumes of fetal brain at different gestational ages and calculated the growth rates of whole brain (0.91+/-0.08 cm(3)/day) and cortical gray matter (0.40+/-0.04 cm(3)/day). We also measured the mean diffusivity in white matter and deep gray matter using diffusion tensor imaging. In conclusion, in utero MRI of fetal baboon brains greatly enhances the use of nonhuman primate models to study fetal brain development longitudinally.