Percent bias and coefficient of variability of mean BPND in simulated occipital cortex and thalamus voxel-wise TACs as a function of simulated noise and application of FA.

Voxelwise Maps to Accompany Fox et al., 2015 PNAS The enclosed .tar.gz file contains voxelwise statistical maps of anxious temperament related metabolism and brian volume, as well as heritability estimates for these measures to acompany Fox AS, et al. (2015). Specifically, it contains: 1) MRI Template: template_meanT1_n592.nii 2) Anixous Temperament related metabolism t-map: FoxEtAl_PNAS_2015_AT_FDGPET_t.nii 3) Anixous Temperament related log jacobian t-map: FoxEtAl_PNAS_2015_AT_LogJacobian_t.nii 4) Heritability of FDG-PET, h^2- and p-maps: FoxEtAl_PNAS_2015_FDGPET_h2.nii FoxEtAl_PNAS_2015_FDGPET_h2_p.nii 5) Heritability of log jacobian determinant, h^2- and p-maps: FoxEtAl_PNAS_2015_LogJacobian_h2.nii FoxEtAl_PNAS_2015_LogJacobian_h2_p.nii Additional information can be found in: Fox AS, Oler JA, Shackman AJ, Shelton SE, Raveendran M, McKay DR, Converse AK, Alexander AL, Davidson RJ, Blangero J, Rogers J, & Kalin NH (2015). Intergenerational neural mediators of early-life anxious temperament. Proceedings of the National Academy of Sciences. In Press.

PurposePET and SPECT voxel kinetics are highly noised. To our knowledge, no study has determined the effect of denoising on the ability to detect differences in binding at the voxel level using Statistical Parametric Mapping (SPM).MethodsIn the present study, groups of subject-images with a 10%- and 20%- difference in binding of [123I]iomazenil (IMZ) were simulated. They were denoised with Factor Analysis (FA). Parametric images of binding potential (BPND) were produced with the simplified reference tissue model (SRTM) and the Logan non-invasive graphical analysis (LNIGA) and analyzed using SPM to detect group differences. FA was also applied to [123I]IMZ and [11C]flumazenil (FMZ) clinical images (n = 4) and the variance of BPND was evaluated.ResultsEstimations from FA-denoised simulated images provided a more favorable bias-precision profile in SRTM and LNIGA quantification. Simulated differences were detected in a higher number of voxels when denoised simulated images were used for voxel-wise estimations, compared to quantification on raw simulated images. Variability of voxel-wise binding estimations on denoised clinical SPECT and PET images was also significantly diminished.ConclusionIn conclusion, noise removal from dynamic brain SPECT and PET images may optimize voxel-wise BPND estimations and detection of biological differences using SPM.

FSL:fd049c96

Collection description

Group-level statistical maps for voxel-wise analyses of grey matter volume, white matter microstructure and resting-state functional connectivity, as detailed in Anatürk et al. (under review). For a detailed key of the images, please see the Supplementary Materials. The types of images currently available are:
_FWER_corr_p_tstat_ = unthresholded images with FWER corrected p-values (Note: 1-p images, therefore please threshold to 0.95 in Neurovault to see results significant at a p < 0.05 level). SOC_{outcome}_{analysis}_{contrast} = images containing t-statistics for social activities. COG_{model}_{outcome}_{analysis}_{contrast} = images containing t-statistics for cognitive activities.

Subject species

homo sapiens

Modality

fMRI-BOLD

Analysis level

group

Cognitive paradigm (task)

rest eyes open

Map type

Other

Structural and diffusion data from cognitively normal elderly and those with mild cognitive impairment. Background and Purpose: To determine if a voxel-wise "co-analysis" of structural and diffusion tensor magnetic resonance imaging (MRI) together reveals additional brain regions affected in mild cognitive impairment (MCI) and Alzheimer's Disease (AD) than voxel-wise analysis of the individual MRI modalities alone. Conclusion: These results suggest that in corpus callosum and temporal regions macroand microstructural variations in MCI can be congruent, providing potentially new insight into the mechanisms of brain tissue degeneration. Methods Methods: Twenty-one patients with MCI, 21 patients with AD, and 21 cognitively normal healthy elderly were studied with MRI. Maps of deformation and fractional anisotropy (FA) were computed and used as dependent variables in univariate and multivariate statistical models. Results: Univariate voxel-wise analysis of macrostructural changes in MCI showed atrophy in the right anterior temporal lobe, left posterior parietal/precuneus region, WM adjacent to the cingulate gyrus, and dorsolateral prefrontal regions, consistent with prior research. Univariate voxel-wise analysis of microstructural changes in MCI showed reduced FA in the left posterior parietal region extending into the corpus callosum, consistent with previous work. The multivariate analysis, which provides more information than univariate tests when structural and FA measures are correlated, revealed additional MCI-related changes in corpus callosum and temporal lobe. Participants: Participants were recruited by advertisements in the community or referred by one of several memory clinics in the San Francisco Bay Area, including the Memory Disorders Clinic at the San Francisco Veterans Affairs Medical Center, the Memory and Aging Center at the University of California, San Francisco, and the Memory Disorders Clinic at the California Pacific Medical Center, for inclusion in one of several studies. Study procedures include a neurological exam, structural MRI, diffusion MRI, and comprehensive neuropsychological testing. In compliance with the Code of Ethics of the World Medical Association and the Declaration of Helsinki, study procedures were approved by review boards of the University of California San Francisco and the San Francisco VA Medical Center, explained to all participants, written informed consent was obtained. From the larger population studied, only participants with artifact-free structural and diffusion MRI were included. Twenty-one patients met Petersen's criteria for MCI, age: 71 ± 8 yrs, 11 women, MMSE (Mini-Mental State Examination): 29 ± 2. These patients were gender matched with 21 cognitively normal healthy elderly controls (CN), age: 70 ± 7 yrs, 11 women, MMSE 29 ± 1. The MCI patients were also gender matched with 21 patients who met AD criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA), age: 69 ± 9, 11 women, MMSE 21 ± 7. As evidenced by the high MMSE scores, the MCI patients were in an early stage of cognitive deficits and far less impaired than the AD patients. Magnetic resonance imaging (MRI) acquisition: All scans were performed on a 4 Tesla (Bruker/Siemens) MRI system with a birdcage transmit and 8 channel receive coil arranged in the same housing. The scans included T1-weighted and T2-weighted structural MRI data for measurements of brain macro-structure and diffusion tensor MRI for measurement of micro-structure. T1-weighted images were obtained with a 3D volumetric magnetization prepared rapid gradient echo (MPRAGE) sequence, TR/TE/TI=2300/3/950 ms, timing; 7º flip angle; 1.0 x 1.0 x 1.0 mm3 resolution; 157 continuous sagittal slices; acquisition time of 5 min. T2-weighted images were acquired with a variable flip (VFL) angle turbo spin-echo sequence with TR/TE = 4000/30 ms and with the same resolution matrix and field of view of MPRAGE. DTI was based on a dual spin-echo refocused echo-planar imaging (EPI) sequence supplemented with parallel imaging acceleration (GRAPPA) (Griswold et al., 2002) with a factor 2 to reduce susceptibility distortions. Other imaging parameters were: TR/TE=6000/77 ms; 2 x 2 mm2 in-plane resolution; 40 continuous 3 mm slices. A reference image (no diffusion gradient b=0) and six diffusion-weighted images (b=800s/mm2 along six non-collinear direction) were acquired. Four DTI scans were acquired and averaged after motion correction to boost signal-to-noise. The total acquisition time of DTI was 4 min. MRI pre-processing: An expectation maximization segmentation (EMS) algorithm including correction for intensity inhomogeneity 30,31 was applied to T1 weighted MRI, separating skull, scalp, extra-cranial tissue from the rest of brain image volume. Each individual skull-stripped and bias field corrected brain image volume was affine registered to a reference brain image to adjust for global differences in brain positioning and scale across individuals. For this study, an unbiased average brain image was used as the reference. The unbiased average brain was generated from 10 healthy elderly individual brains (i.e., age of 50 to 70) that were not part of the CN group using an unbiased atlas formation technique based on large deformations mapping 32. A large deformation diffeomorphic mapping algorithm using fluid-flow registration 33 was used to register individual scans to standard image space of the unbiased atlas brain. The Jacobian determinant of this transformation was computed at each voxel (resolution 1x1x1 mm3), giving the pattern of volume change required to force the individual anatomy to conform to the reference. The Jacobian images were log transformed to achieve a more normal distribution and then smoothed using a Gaussian filter (FWHM=10 mm) to create tissue volume maps (JAC), where the value at each voxel represents the tissue volume relative to the reference (e.g., a voxel value of 0.06 denotes a volume volrefx100.06, or about 15 percent greater than the reference voxel) DTI pre-processing: The pre-processing pipeline aims to align a set of DTI images with the corresponding structural data through the following steps. Diffusion tensor images were corrected for eddy currents and head motion 34. Based on a mutual information metric, the T2-weighted image was rigidly aligned to the B0 image, which is a DTI maps without diffusion sensing gradients (b=0 s/mm2). A variational image-based approach was used to calculate a deformation field from the B0 image to the rigidly aligned T2-weighted image to correct for susceptibility artifacts (i.e., nonlinear geometric distortion in DTI) 35. We selected a variational approach for EPI distortion correction over the conventional field map approach, because studies have shown that the local deformations in EPI are best handled with a dense displacement field (i.e. high order deformations) 35. In contrast, field maps can fail to completely correct geometric distortions, presumably due to limits in the physical model 36. Concatenated eddy current transformation and the deformation field for nonlinear distortion correction were applied to all DTIs. Diffusion tensors were estimated for each subject from the diffusion tensor images using weighted least squares tensor estimation 37. The T2-weighted image was rigidly aligned to the T1-weighted image and the transformation was concatenated with the inverse rigid transformation from B0 image to T2-weighted image. The resulting rigid transformation was applied to the FA image to map onto the T1-weighted structural image space of the subject. The FA image was then mapped onto the standard image space by applying the diffeomorphic mapping estimated in MRI pre-processing. FA images were then smoothed using a Gaussian filter (FWHM=10 mm) in the standard image space.

• Refers to statistical significant differences.FWE indicates Family-wise error.a Each region was circumscribed using the small volume correction (SVC) approach, with anatomically defined volume-of-interest masks.bNumber of contiguous voxels that surpassed the initial threshold of p<0.001 (uncorrected) in the statistical parametric maps.cZ scores for the voxel of maximal statistical significance.dMNI coordinates of the voxel of maximal statistical significance within each cluster.eStatistical significance after correction for multiple comparisons; inferences made at the level of individual voxels (FWE- correction for multiple comparisonsVoxelwise differences between subjects with low education (n = 122) and high education (n = 66) in the significance of linear correlations between regional gray matter volumes and age.

Neurons project long axons that contact other distant neurons. Neurons in the medial prefrontal cortex project into the limbic system to regulate responses to reward or threat. Diminished neural activity in prefrontal cortex is associated with loss of executive function leading to drug use, yet the specific circuitry that mediate these effects is unknown. Different regions within the medial prefrontal cortex may project to differing limbic system nuclei. Here, we exploited the cell biology of intracellular membrane trafficking, fast axonal transport, to map projections from two adjacent medial prefrontal cortical regions. We used Mn(II), a calcium analog, to trace medial prefrontal cortical projections in the living animal by magnetic resonance imaging (MRI). Mn(II), a contrast agent for MRI, enters neurons through voltage-activated calcium channels and relies on kinesin-1 and amyloid-precursor protein to transport out axons to distal destinations. Aqueous MnCl2 together with fluorescent dextran (3–-5 nL) was stereotactically injected precisely into two adjacent regions of the medial prefrontal cortex: anterior cingulate area (ACA) or infralimbic/prelimbic (IL/PL) region. Projections were traced, first live by manganese-enhanced MRI (MEMRI) at four time points in 3D, and then after fixation by microscopy. Data-driven unbiased voxel-wise statistical maps of aligned normalized MR images after either ACA or IL/PL injections revealed statistically significant progression of Mn(II) over time into deeper brain regions: dorsal striatum, globus pallidus, amygdala, hypothalamus, substantia nigra, dorsal raphe and locus coeruleus. Quantitative comparisons of these distal accumulations at 24 h revealed dramatic differences between ACA and IL/PL injection groups throughout the limbic system, and most particularly in subdomains of the hypothalamus. ACA projections targeted dorsomedial nucleus of the hypothalamus, posterior part of the periventricular region and mammillary body nuclei as well as periaqueductal gray, while IL/PL projections accumulated in anterior hypothalamic areas and lateral hypothalamic nuclei as well as amygdala. As hypothalamic subsegments relay CNS activity to the body, our results suggest new concepts about mind-body relationships and specific roles of distinct yet adjacent medial prefrontal cortical segments. Our MR imaging strategy, when applied to follow other cell biological processes in the living organism, will undoubtedly lead to an expanded perspective on how minute details of cellular processes influence whole body health and wellbeing.

SPM{T_[93.0]} - contrast 5: INSO>NC

Collection description

The un-thresholded voxel-wise statistical maps of this research

Subject species

homo sapiens

Modality

fMRI-BOLD

Analysis level

group

Cognitive paradigm (task)

None / Other

Map type

T

Amyloid precursor protein (APP) is the precursor to Aβ plaques. The cytoplasmic domain of APP mediates attachment of vesicles to molecular motors for axonal transport. In APP-KO mice, transport of Mn2+ is decreased. In old transgenic mice expressing mutated human (APPSwInd) linked to Familial Alzheimer’s Disease, with both expression of APPSwInd and plaques, the rate and destination of Mn2+ axonal transport is altered, as detected by time-lapse manganese-enhanced magnetic resonance imaging (MEMRI) of the brain in living mice. To determine the relative contribution of expression of APPSwInd versus plaque on transport dynamics, we developed a Tet-off system to decouple expression of APPSwInd from plaque, and then studied hippocampal to forebrain transport by MEMRI. Three groups of mice were compared to wild-type (WT): Mice with plaque and APPSwInd expression; mice with plaque but suppression of APPSwInd expression; and mice with APPSwInd suppressed from mating until 2 weeks before imaging with no plaque. MR images were captured before at successive time points after stereotactic injection of Mn2+ (3–5 nL) into CA3 of the hippocampus. Mice were returned to their home cage between imaging sessions so that transport would occur in the awake freely moving animal. Images of multiple mice from the three groups (suppressed or expressed) together with C57/B6J WT were aligned and processed with our automated computational pipeline, and voxel-wise statistical parametric mapping (SPM) performed. At the conclusion of MR imaging, brains were harvested for biochemistry or histopathology. Paired T-tests within-group between time points (p = 0.01 FDR corrected) support the impression that both plaque alone and APPSwInd expression alone alter transport rates and destination of Mn2+ accumulation. Expression of APPSwInd in the absence of plaque or detectable Aβ also resulted in transport defects as well as pathology of hippocampus and medial septum, suggesting two sources of pathology occur in familial Alzheimer’s disease, from toxic mutant protein as well as plaque. Alternatively mice with plaque without APPSwInd expression resemble the human condition of sporadic Alzheimer’s, and had better transport. Thus, these mice with APPSwInd expression suppressed after plaque formation will be most useful in preclinical trials.

Overall summary MKDA map, thresholded for significance using an “extent-based” threshold, voxel- wise alpha 0.01, resulting in FWER corrected threshold, p < 0.05.

Collection description

Communication between the brain and peripheral mediators of systemic inflammation is implicated in numerous psychological, behavioral, and physiological processes. Functional neuroimaging studies have identified brain regions that associate with peripheral inflammation in humans, yet there are open questions about the consistency, specificity, and network characteristics of these findings. The present systematic review provides a meta-analysis to address these questions. Multilevel kernel density analysis of 24 studies (37 statistical maps; 264 coordinates; 457 participants) revealed consistent effects in the amygdala, hippocampus, hypothalamus, striatum, insula, midbrain, and brainstem, as well as prefrontal and temporal cortices. Effects in some regions were specific to particular study designs and tasks. Spatial pattern analysis revealed significant overlap of reported effects with limbic, default mode, ventral attention, and corticostriatal networks, and co-activation analyses revealed functional ensembles encompassing the prefrontal cortex, insula, and midbrain/brainstem. Together, these results characterize brain regions and networks associated with peripheral inflammation in humans, and they provide a functional neuroanatomical reference point for future neuroimaging studies on brain-body interactions.

Subject species

homo sapiens

Modality

Other

Analysis level

meta-analysis

Cognitive paradigm (task)

None / Other

Map type

R

For contrasting case-control differences, we run voxel-wise statistics for AD using a nonparametric permutation-based approach (FSL, Randomise, 5000 permutations). Age and sex were entered as covariates. All covariates were demeaned. The map shows family-wise-error-corrected values using threshold free cluster enhancement (see https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Randomise/UserGuide).

Collection description

Unthresholded t- and corrected p-maps of the scalar diffusion measures fractional anistropy (FA), axial diffusivity (AD) and radial diffusivity (RD), contrasting adolescent patients with early onset psychosis versus adolescent healthy controls (i.e. contrast 1: patients >controls; contrast 2: patients > controls, covariates: age and sex).

Preprint: https://www.biorxiv.org/content/10.1101/721225v2

Subject species

homo sapiens

Modality

Diffusion MRI

Analysis level

group

Cognitive paradigm (task)

None / Other

Map type

IP