Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

INTRODUCTION: The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology. METHODS: We imaged post mortem human tissue at 100 µm3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case). Vessel density was quantified and compared per EC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores. RESULTS: PC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden. DISCUSSION: These data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context. HIGHLIGHTS: Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.

Tracing Modification to Cortical Circuits in Human and Nonhuman Primates from High-Resolution Tractography, Transcription, and Temporal Dimensions.

The neural circuits that support human cognition are a topic of enduring interest. Yet, there are limited tools available to map brain circuits in the human and nonhuman primate brain. We harnessed high-resolution diffusion MR tractography, anatomic, and transcriptomic data from individuals of either sex to investigate the evolution and development of frontal cortex circuitry. We applied machine learning to RNA sequencing data to find corresponding ages between humans and macaques and to compare the development of circuits across species. We transcriptionally defined neural circuits by testing for associations between gene expression and white matter maturation. We then considered transcriptional and structural growth to test whether frontal cortex circuit maturation is unusually extended in humans relative to other species. We also considered gene expression and high-resolution diffusion MR tractography of adult brains to test for cross-species variation in frontal cortex circuits. We found that frontal cortex circuitry development is extended in primates, and concomitant with an expansion in corticocortical pathways compared with mice in adulthood. Importantly, we found that these parameters varied relatively little across humans and studied primates. These data identify a surprising collection of conserved features in frontal cortex circuits across humans and Old World monkeys. Our work demonstrates that integrating transcriptional and structural data across temporal dimensions is a robust approach to trace the evolution of brain pathways in primates.SIGNIFICANCE STATEMENT Diffusion MR tractography is an exciting method to explore pathways, but there are uncertainties in the accuracy of reconstructed tracts. We broaden the repertoire of toolkits to enhance our ability to trace human brain pathways from diffusion MR tractography. Our integrative approach finds corresponding ages across species and transcriptionally defines neural circuits. We used this information to test for variation in circuit maturation across species and found a surprising constellation of similar features in frontal cortex neural circuits across humans and primates. Integrating across scales of biological organization expands the repertoire of tools available to study pathways in primates, which opens new avenues to study pathways in health and diseases of the human brain.

Multimodal magnetic resonance neuroimaging measures characteristic of early cART-treated pediatric HIV: A feature selection approach.

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV-related brain alterations can be investigated separately using proton magnetic resonance spectroscopy (1 H-MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI), a set of multimodal MRI measures characteristic of children on cART has not been previously identified. We used the embedded feature selection of a logistic elastic-net (EN) regularization to select neuroimaging measures that distinguish CPHIV from controls and measured their classification performance via the area under the receiver operating characteristic curve (AUC) using repeated cross validation. We also wished to establish whether combining MRI modalities improved the models. In single modality analysis, sMRI volumes performed best followed by DTI, whereas individual EN models on spectroscopic, gyrification, and cortical thickness measures showed no class discrimination capability. Adding DTI and 1 H-MRS in basal measures to sMRI volumes produced the highest classification performance validation accuracy = 85 % AUC = 0.80 . The best multimodal MRI set consisted of 22 DTI and sMRI volume features, which included reduced volumes of the bilateral globus pallidus and amygdala, as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the right corticospinal tract in cART-treated CPHIV. Consistent with previous studies of CPHIV, select subcortical volumes obtained from sMRI provide reasonable discrimination between CPHIV and controls. This may give insight into neuroimaging measures that are relevant in understanding the effects of HIV on the brain, thereby providing a starting point for evaluating their link with cognitive performance in CPHIV.

Self-navigated prospective motion correction for 3D-EPI acquisition.

PURPOSE: Although 3D EPI is more susceptible to motion artifacts than 2D EPI, it presents some benefits for functional MRI, including the absence of spin-history artifacts, greater potential for parallel imaging acceleration, and better functional sensitivity in high-resolution imaging. Here we present a self-navigated 3D-EPI sequence suitable for prospective motion-corrected functional MRI without additional hardware or pulses. METHODS: For each volume acquisition, the first 24 of the 52 partitions being acquired are accumulated to a new feedback block that was added to the image reconstruction pipeline. After zero-filling the remaining partitions, the feedback block constructs a volumetric self-navigator (vSNav), co-registers it to the reference vSNav acquired during the first volume acquisition, and sends motion estimates to the sequence. The sequence then updates its FOV and acquires subsequent partitions with the adjusted FOV, until the next update is received. The sequence was validated without and with intentional motion in phantom and in vivo on a 3T Skyra. RESULTS: For phantom scans, the FOV was updated 0.704 s after acquisition of the vSNav partitions, and for in vivo scans after 0.768 s. Both phantom and in vivo data demonstrated stable motion estimates in the absence of motion. For in vivo acquisitions, prospective head-pose estimates using the vSNav's and retrospective estimates with FLIRT (FMRIB's Linear Image Registration Tool) agreed to within 0.23 mm (< 10% of the slice thickness) and 0.14° in all directions. CONCLUSION: Depending when motion occurs during a volume acquisition, the proposed method fully corrects the FOV and recovers image quality within one volume acquisition.

Perivascular space dilation is associated with vascular amyloid-ß accumulation in the overlying cortex.

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-ß (Aß) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular Aß accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD.

Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. METHODS: Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. RESULTS: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (ß ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. CONCLUSIONS: High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans.

Brain Wiring and Supragranular-Enriched Genes Linked to Protracted Human Frontal Cortex Development.

The human frontal cortex is unusually large compared with many other species. The expansion of the human frontal cortex is accompanied by both connectivity and transcriptional changes. Yet, the developmental origins generating variation in frontal cortex circuitry across species remain unresolved. Nineteen genes that encode filaments, synapse, and voltage-gated channels are especially enriched in the supragranular layers of the human cerebral cortex, which suggests enhanced corticocortical projections emerging from layer III. We identify species differences in connections with the use of diffusion MR tractography as well as gene expression in adulthood and in development to identify developmental mechanisms generating variation in frontal cortical circuitry. We demonstrate that increased expression of supragranular-enriched genes in frontal cortex layer III is concomitant with an expansion in corticocortical pathways projecting within the frontal cortex in humans relative to mice. We also demonstrate that the growth of the frontal cortex white matter and transcriptional profiles of supragranular-enriched genes are protracted in humans relative to mice. The expansion of projections emerging from the human frontal cortex arises by extending frontal cortical circuitry development. Integrating gene expression with neuroimaging level phenotypes is an effective strategy to assess deviations in developmental programs leading to species differences in connections.

Different microvascular alterations underlie microbleeds and microinfarcts.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid ß (Aß) in the walls of cortical vessels and the accrual of microbleeds and microinfarcts over time. The relationship between CAA severity and microbleeds and microinfarcts as well as the sequence of events that lead to lesion formation remain poorly understood. METHODS: We scanned intact formalin-fixed hemispheres of 12 CAA cases with magnetic resonance imaging (MRI), followed by histopathological examination in predefined areas and serial sectioning in targeted areas with multiple lesions. RESULTS: In total, 1,168 cortical microbleeds and 472 cortical microinfarcts were observed on ex vivo MRI. Increasing CAA severity at the whole-brain or regional level was not associated with the number of microbleeds or microinfarcts. However, locally, the density of Aß-positive cortical vessels was lower surrounding a microbleed compared to a simulated control lesion, and higher surrounding microinfarcts. Serial sectioning revealed that for (n = 28) microbleeds, both Aß (4%) and smooth muscle cells (4%) were almost never present in the vessel wall at the site of bleeding, but Aß was frequently observed upstream or downstream (71%), as was extensive fibrin(ogen) buildup (87%). In contrast, for (n = 22) microinfarcts, vascular Aß was almost always observed at the core of the lesion (91%, p < 0.001) as well as upstream or downstream (82%), but few vessels associated with microinfarcts had intact smooth muscle cells (9%). INTERPRETATION: These observations provide a model for how a single neuropathologic process such as CAA may result in hemorrhagic or ischemic brain lesions potentially through 2 different mechanistic pathways. ANN NEUROL 2019;86:279-292.

Histopathology of diffusion-weighted imaging-positive lesions in cerebral amyloid angiopathy.

Small subclinical hyperintense lesions are frequently encountered on brain diffusion-weighted imaging (DWI) scans of patients with cerebral amyloid angiopathy (CAA). Interpretation of these DWI+ lesions, however, has been limited by absence of histopathological examination. We aimed to determine whether DWI+ lesions represent acute microinfarcts on histopathology in brains with advanced CAA, using a combined in vivo MRI-ex vivo MRI-histopathology approach. We first investigated the histopathology of a punctate cortical DWI+ lesion observed on clinical in vivo MRI 7 days prior to death in a CAA case. Subsequently, we assessed the use of ex vivo DWI to identify similar punctate cortical lesions post-mortem. Intact formalin-fixed hemispheres of 12 consecutive cases with CAA and three non-CAA controls were subjected to high-resolution 3 T ex vivo DWI and T2 imaging. Small cortical lesions were classified as either DWI+/T2+ or DWI-/T2+. A representative subset of lesions from three CAA cases was selected for detailed histopathological examination. The DWI+ lesion observed on in vivo MRI could be matched to an area with evidence of recent ischemia on histopathology. Ex vivo MRI of the intact hemispheres revealed a total of 130 DWI+/T2+ lesions in 10/12 CAA cases, but none in controls (p = 0.022). DWI+/T2+ lesions examined histopathologically proved to be acute microinfarcts (classification accuracy 100%), characterized by presence of eosinophilic neurons on hematoxylin and eosin and absence of reactive astrocytes on glial fibrillary acidic protein-stained sections. In conclusion, we suggest that small DWI+ lesions in CAA represent acute microinfarcts. Furthermore, our findings support the use of ex vivo DWI as a method to detect acute microinfarcts post-mortem, which may benefit future histopathological investigations on the etiology of microinfarcts.

Real-time simultaneous shim and motion measurement and correction in glycoCEST MRI using double volumetric navigators (DvNavs).

PURPOSE: CEST MRI allows for indirect detection of molecules with exchangeable protons, measured as a reduction in water signal because of continuous transfer of saturated protons. CEST requires saturation pulses on the order of a second, as well as repeated acquisitions at different offset frequencies. The resulting extended scan time makes CEST susceptible to subject motion, which introduces field inhomogeneity, shifting offset frequencies and causing distortions in CEST spectra that resemble true CEST effects. This is a particular problem for molecules that resonate close to water, such as hydroxyl group in glycogen. To address this, a technique for real-time measurement and correction of motion and field inhomogeneity is proposed. METHODS: A CEST sequence was modified to include double volumetric navigators (DvNavs) for real-time simultaneous motion and shim correction. Phantom tests were conducted to investigate the effects of motion and shim changes on CEST quantification and to validate the accuracy of DvNav motion and shim estimates. To evaluate DvNav shim and motion correction in vivo, acquisitions including 5 experimental conditions were performed in the calf muscle of 2 volunteers. RESULTS: Phantom data show that DvNav-CEST accurately estimates frequency and linear gradient changes because of motion and corrects resulting image distortions. In addition, DvNav-CEST improves CEST quantification in vivo in the presence of motion. CONCLUSION: The proposed technique allows for real-time simultaneous motion and shim correction with no additional scanning time, enabling accurate CEST quantification even in the presence of motion and field inhomogeneity.

Real-time Correction of Motion and Imager Instability Artifacts during 3D γ-Aminobutyric Acid-edited MR Spectroscopic Imaging.

Purpose To compare the involuntary head motion, frequency and B0 shim changes, and effects on data quality during real-time-corrected three-dimensional γ-aminobutyric acid-edited magnetic resonance (MR) spectroscopic imaging in subjects with mild cognitive impairment (MCI), patients with Parkinson disease (PD), and young and older healthy volunteers. Materials and Methods In this prospective study, MR spectroscopic imaging datasets were acquired at 3 T after written informed consent was obtained. Translational and rotational head movement, frequency, and B0 shim were determined with an integrated volumetric navigator. Head motion patterns and imager instability were investigated in 33 young healthy control subjects (mean age ± standard deviation, 31 years ± 5), 34 older healthy control subjects (mean age, 67 years ± 8), 34 subjects with MCI (mean age, 72 years ± 5), and 44 patients with PD (mean age, 64 years ± 8). Spectral quality was assessed by means of region-of-interest analysis. Group differences were evaluated with Bonferroni-corrected Mann-Whitney tests. Results Three patients with PD and four subjects with MCI were excluded because of excessive head motion (ie, > 0.8 mm translation per repetition time of 1.6 seconds throughout >10 minutes). Older control subjects, patients with PD, and subjects with MCI demonstrated 1.5, 2, and 2.5 times stronger head movement, respectively, than did young control subjects (1.79 mm ± 0.77) (P < .001). Of young control subjects, older control subjects, patients with PD, and subjects with MCI, 6%, 35%, 38%, and 51%, respectively, moved more than 3 mm during the MR spectroscopic imaging acquisition of approximately 20 minutes. The predominant movements were head nodding and "sliding out" of the imager. Frequency changes were 1.1- and 1.4-fold higher in patients with PD (P = .007) and subjects with MCI (P < .001), respectively, and B0 shim changes were 1.3-, 1.5-, and 1.9-fold higher in older control subjects (P = .005), patients with PD (P < .001), and patients with MCI (P < .001), respectively, compared with those of young control subjects (12.59 Hz ± 2.49, 3.61 Hz · cm-1 ± 1.25). Real-time correction provided high spectral quality in all four groups (signal-to-noise ratio >15, Cramér-Rao lower bounds < 20%). Conclusion Real-time motion and B0 monitoring provides valuable information about motion patterns and B0 field variations in subjects with different predispositions for head movement. Immediate correction improves data quality, particularly in patients who have difficulty avoiding movement. © RSNA, 2017 Online supplemental material is available for this article.

Heavy Prenatal Alcohol Exposure is Related to Smaller Corpus Callosum in Newborn MRI Scans.

BACKGROUND: Magnetic resonance imaging (MRI) studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure (PAE) but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate PAE effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC). METHODS: Forty-three nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost 2-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and fetal alcohol spectrum disorders diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains. RESULTS: CC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy. CONCLUSIONS: Given that midline craniofacial anomalies have been recognized as a hallmark of fetal alcohol syndrome in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence.

Microbleed and microinfarct detection in amyloid angiopathy: a high-resolution MRI-histopathology study.

Cerebral amyloid angiopathy is a common neuropathological finding in the ageing human brain, associated with cognitive impairment. Neuroimaging markers of severe cerebral amyloid angiopathy are cortical microbleeds and microinfarcts. These parenchymal brain lesions are considered key contributors to cognitive impairment. Therefore, they are important targets for therapeutic strategies and may serve as surrogate neuroimaging markers in clinical trials. We aimed to gain more insight into the pathological basis of magnetic resonance imaging-defined microbleeds and microinfarcts in cerebral amyloid angiopathy, and to explore the pathological burden that remains undetected, by using high and ultra-high resolution ex vivo magnetic resonance imaging, as well as detailed histological sampling. Brain samples from five cases (mean age 85 ± 6 years) with pathology-proven cerebral amyloid angiopathy and multiple microbleeds on in vivo clinical magnetic resonance imaging were subjected to high-resolution ex vivo 7 T magnetic resonance imaging. On the obtained high-resolution (200 µm isotropic voxels) ex vivo magnetic resonance images, 171 microbleeds were detected compared to 66 microbleeds on the corresponding in vivo magnetic resonance images. Of 13 sampled microbleeds that were matched on histology, five proved to be acute and eight old microhaemorrhages. The iron-positive old microhaemorrhages appeared approximately four times larger on magnetic resonance imaging compared to their size on histology. In addition, 48 microinfarcts were observed on ex vivo magnetic resonance imaging in three out of five cases (two cases exhibited no microinfarcts). None of them were visible on in vivo 1.5 T magnetic resonance imaging after a retrospective analysis. Of nine sampled microinfarcts that were matched on histology, five were confirmed as acute and four as old microinfarcts. Finally, we explored the proportion of microhaemorrhage and microinfarct burden that is beyond the detection limits of ex vivo magnetic resonance imaging, by scanning a smaller sample at ultra-high resolution, followed by serial sectioning. At ultra-high resolution (75 µm isotropic voxels) magnetic resonance imaging we observed an additional 48 microbleeds (compared to high resolution), which proved to correspond to vasculopathic changes (i.e. morphological changes to the small vessels) instead of frank haemorrhages on histology. After assessing the serial sections of this particular sample, no additional haemorrhages were observed that were missed on magnetic resonance imaging. In contrast, nine microinfarcts were found in these sections, of which six were only retrospectively visible at ultra-high resolution. In conclusion, these findings suggest that microbleeds on in vivo magnetic resonance imaging are specific for microhaemorrhages in cerebral amyloid angiopathy, and that increasing the resolution of magnetic resonance images results in the detection of more 'non-haemorrhagic' pathology. In contrast, the vast majority of microinfarcts currently remain under the detection limits of clinical in vivo magnetic resonance imaging.

Real-time measurement and correction of both B0 changes and subject motion in diffusion tensor imaging using a double volumetric navigated (DvNav) sequence.

Diffusion tensor imaging (DTI) requires a set of diffusion weighted measurements in order to acquire enough information to characterize local structure. The MRI scanner automatically performs a shimming process by acquiring a field map before the start of a DTI scan. Changes in B0, which can occur throughout the DTI acquisition due to several factors (including heating of the iron shim coils or subject motion), cause significant signal distortions that result in warped diffusion tensor (DT) parameter estimates. In this work we introduce a novel technique to simultaneously measure, report and correct in real time subject motion and changes in B0 field homogeneity, both in and through the imaging plane. This is achieved using double volumetric navigators (DvNav), i.e. a pair of 3D EPI acquisitions, interleaved with the DTI pulse sequence. Changes in the B0 field are evaluated in terms of zero-order (frequency) and first-order (linear gradients) shim. The ability of the DvNav to accurately estimate the shim parameters was first validated in a water phantom. Two healthy subjects were scanned both in the presence and absence of motion using standard, motion corrected (single navigator, vNav), and DvNav DTI sequences. The difference in performance between the proposed 3D EPI field maps and the standard 3D gradient echo field maps of the MRI scanner was also evaluated in a phantom and two healthy subjects. The DvNav sequence was shown to accurately measure and correct changes in B0 following manual adjustments of the scanner's central frequency and the linear shim gradients. Compared to other methods, the DvNav produced DTI results that showed greater spatial overlap with anatomical references, particularly in scans with subject motion. This is largely due to the ability of the DvNav system to correct shim changes and subject motion between each volume acquisition, thus reducing shear distortion.

Prospective motion correction with volumetric navigators (vNavs) reduces the bias and variance in brain morphometry induced by subject motion.

Recent work has demonstrated that subject motion produces systematic biases in the metrics computed by widely used morphometry software packages, even when the motion is too small to produce noticeable image artifacts. In the common situation where the control population exhibits different behaviors in the scanner when compared to the experimental population, these systematic measurement biases may produce significant confounds for between-group analyses, leading to erroneous conclusions about group differences. While previous work has shown that prospective motion correction can improve perceived image quality, here we demonstrate that, in healthy subjects performing a variety of directed motions, the use of the volumetric navigator (vNav) prospective motion correction system significantly reduces the motion-induced bias and variance in morphometry.

Dense, shape-optimized posterior 32-channel coil for submillimeter functional imaging of visual cortex at 3T.

PURPOSE: Functional neuroimaging of small cortical patches such as columns is essential for testing computational models of vision, but imaging from cortical columns at conventional 3T fields is exceedingly difficult. By targeting the visual cortex exclusively, we tested whether combined optimization of shape, coil placement, and electronics would yield the necessary gains in signal-to-noise ratio (SNR) for submillimeter visual cortex functional MRI (fMRI). METHOD: We optimized the shape of the housing to a population-averaged atlas. The shape was comfortable without cushions and resulted in the maximally proximal placement of the coil elements. By using small wire loops with the least number of solder joints, we were able to maximize the Q factor of the individual elements. Finally, by planning the placement of the coils using the brain atlas, we were able to target the arrangement of the coil elements to the extent of the visual cortex. RESULTS: The combined optimizations led to as much as two-fold SNR gain compared with a whole-head 32-channel coil. This gain was reflected in temporal SNR as well and enabled fMRI mapping at 0.75 mm resolutions using a conventional GRAPPA-accelerated gradient echo echo planar imaging. CONCLUSION: Integrated optimization of shape, electronics, and element placement can lead to large gains in SNR and empower submillimeter fMRI at 3T. Magn Reson Med 76:321-328, 2016. © 2015 Wiley Periodicals, Inc.

Prospective motion correction and selective reacquisition using volumetric navigators for vessel-encoded arterial spin labeling dynamic angiography.

PURPOSE: The aim of this study was to improve robustness to motion in a vessel-encoded angiography sequence used for patient scans. The sequence is particularly sensitive to motion between imaging segments, which causes ghosting and blurring that propagates to the final angiogram. METHODS: Volumetric echo planar imaging (EPI) navigators acquired in 275 ms were inserted after the imaging readout in a vessel-encoded pseudo-continuous arterial spin labeling (VEPCASL) sequence. The effects of movement between segments on the images were tested with phantom experiments. Deliberate motion experiments with healthy volunteers were performed to compare prospective motion correction (PMC) with reacquisition versus no correction. RESULTS: In scans without motion, the addition of the EPI navigator to the sequence did not affect the quality of the angiograms in comparison with the original sequence. PMC and reacquisition improved the visibility of vessels in the angiograms compared with the scans without correction. The reacquisition strategy was shown to be important for complete correction of imaging artifacts. CONCLUSION: We have demonstrated an effective method to correct motion in vessel-encoded angiography. For reacquisition of 15 segments, the technique requires approximately 30 s of additional scanning (∼25%). Magn Reson Med 76:1420-1430, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Volumetric navigated MEGA-SPECIAL for real-time motion and shim corrected GABA editing.

Mescher-Garwood (MEGA) editing with spin echo full intensity acquired localization (MEGA-SPECIAL, MSpc) is a technique to acquire γ-aminobutyric acid (GABA) without macromolecule (MM) contamination at a TE of 68 ms. However, due to the requirement of multiple shot-localization, it is often susceptible to subject motion and B0 inhomogeneity. A method is presented for real-time shim and motion correction (ShMoCo) using volumetric navigators to correct for motion and motion-related B0 inhomogeneity during MSpc acquisition. A phantom experiment demonstrates that ShMoCo restores the GABA peak and improves spectral quality in the presence of motion and zero- and first-order shim changes. The ShMoCo scans were validated in three subjects who performed up-down and left-right head rotations. Qualitative assessment of these scans indicates effective reduction of subtraction artefacts and well edited GABA peaks, while quantitative analysis indicates superior fitting and spectral quality relative to scans with no correction. Copyright © 2015 John Wiley & Sons, Ltd.

Reproducibility of macromolecule suppressed GABA measurement using motion and shim navigated MEGA-SPECIAL with LCModel, jMRUI and GANNET.

OBJECTIVE: Measuring the pure form of GABA has become increasingly important because of its association with behaviour and certain pathologies. The aim of this study was to assess the reproducibility of GABA measurements using a shim and motion navigated MEGA-SPECIAL sequence with LCModel, jMRUI and GANNET software. MATERIALS AND METHODS: Motion and shim navigated MEGA-SPECIAL scans were acquired in 20 healthy subjects. Two acquisitions were performed for each of two regions: the anterior cingulate (ACC) and medial-parietal (PAR) cortices. Absolute GABA concentration ([Formula: see text]) and GABA-to-Creatine ratio (GABA/Cr) were quantified using the three software packages. RESULTS: Using the within-subject coefficient of variation (CVws) as an index, reproducibility for both GABAH20 and GABA/Cr ranged from 13 to 22 % in the ACC and 13 to 18 % in PAR using the three software packages. CONCLUSION: Based on CVws, GABA concentrations in both the ACC and PAR are reproducible using a shim and motion navigated MEGA-SPECIAL sequence with any of the three software packages, thus demonstrating the ability to quantify the pure form of GABA using these software in studies relating GABA to pathology and healthy behaviour.

Head motion during MRI acquisition reduces gray matter volume and thickness estimates.

Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal development, disease, and the effects of disease-modifying therapies. However, motion during image acquisition introduces image artifacts that, in turn, affect derived markers. A systematic effect can be problematic since factors of interest like age, disease, and treatment are often correlated with both a structural change and the amount of head motion in the scanner, confounding the ability to distinguish biology from artifact. Here we evaluate the effect of head motion during image acquisition on morphometric estimates of structures in the human brain using several popular image analysis software packages (FreeSurfer 5.3, VBM8 SPM, and FSL Siena 5.0.7). Within-session repeated T1-weighted MRIs were collected on 12 healthy volunteers while performing different motion tasks, including two still scans. We show that volume and thickness estimates of the cortical gray matter are biased by head motion with an average apparent volume loss of roughly 0.7%/mm/min of subject motion. Effects vary across regions and remain significant after excluding scans that fail a rigorous quality check. In view of these results, the interpretation of reported morphometric effects of movement disorders or other conditions with increased motion tendency may need to be revisited: effects may be overestimated when not controlling for head motion. Furthermore, drug studies with hypnotic, sedative, tranquilizing, or neuromuscular-blocking substances may contain spurious "effects" of reduced atrophy or brain growth simply because they affect motion distinct from true effects of the disease or therapeutic process.