Combining arterial blood contrast with BOLD increases fMRI intracortical contrast.

BOLD fMRI is widely applied in human neuroscience but is limited in its spatial specificity due to a cortical-depth-dependent venous bias. This reduces its localization specificity with respect to neuronal responses, a disadvantage for neuroscientific research. Here, we modified a submillimeter BOLD protocol to selectively reduce venous and tissue signal and increase cerebral blood volume weighting through a pulsed saturation scheme (dubbed Arterial Blood Contrast) at 7 T. Adding Arterial Blood Contrast on top of the existing BOLD contrast modulated the intracortical contrast. Isolating the Arterial Blood Contrast showed a response free of pial-surface bias. The results suggest that Arterial Blood Contrast can modulate the typical fMRI spatial specificity, with important applications in in-vivo neuroscience.

A selection and targeting framework of cortical locations for line-scanning fMRI.

Depth-resolved functional magnetic resonance imaging (fMRI) is an emerging field growing in popularity given the potential of separating signals from different computational processes in cerebral cortex. Conventional acquisition schemes suffer from low spatial and temporal resolutions. Line-scanning methods allow depth-resolved fMRI by sacrificing spatial coverage to sample blood oxygenated level-dependent (BOLD) responses at ultra-high temporal and spatial resolution. For neuroscience applications, it is critical to be able to place the line accurately to (1) sample the right neural population and (2) target that neural population with tailored stimuli or tasks. To this end, we devised a multi-session framework where a target cortical location is selected based on anatomical and functional properties. The line is then positioned according to this information in a separate second session, and we tailor the experiment to focus on the target location. Anatomically, the precision of the line placement was confirmed by projecting a nominal representation of the acquired line back onto the surface. Functional estimates of neural selectivities in the line, as quantified by a visual population-receptive field model, resembled the target selectivities well for most subjects. This functional precision was quantified in detail by estimating the distance between the visual field location of the targeted vertex and the location in visual cortex (V1) that most closely resembled the line-scanning estimates; this distance was on average ~5.5 mm. Given the dimensions of the line, differences in acquisition, session, and stimulus design, this validates that line-scanning can be used to probe local neural sensitivities across sessions. In summary, we present an accurate framework for line-scanning MRI; we believe such a framework is required to harness the full potential of line-scanning and maximize its utility. Furthermore, this approach bridges canonical fMRI experiments with electrophysiological experiments, which in turn allows novel avenues for studying human physiology non-invasively.

High-Resolution Motion-corrected 7.0-T MRI to Derive Morphologic Measures from the Human Cerebellum in Vivo.

Background The human cerebellum has a large, highly folded cortical sheet. Its visualization is important for various disorders, including multiple sclerosis and spinocerebellar ataxias. The derivation of the cerebellar cortical surface in vivo is impeded by its high foliation. Purpose To image the cerebellar cortex, including its foliations and lamination, in less than 20 minutes, reconstruct the cerebellocortical surface, and extract cortical measures with use of motion-corrected, high-spatial-resolution 7.0-T MRI. Materials and Methods In this prospective study, conducted between February 2021 and July 2022, healthy participants underwent an examination with either a 0.19 × 0.19 × 0.5-mm3, motion-corrected fast low-angle shot (FLASH) sequence (14.5 minutes) or a whole-cerebellum 0.4 × 0.4 × 0.4-mm3, motion-corrected magnetization-prepared 2 rapid gradient-echo (MP2RAGE) sequence (18.5 minutes) at 7.0 T. Four participants underwent an additional FLASH sequence without motion correction. FLASH and MP2RAGE sequences were used to visualize the cerebellar cortical layers, derive cerebellar gray and white matter segmentations, and examine their fidelity. Quantitative measures were compared using repeated-measures analyses of variance or paired t tests. Results Nine participants (median age, 36 years [IQR, 25-42 years; range, 21-62 years]; five women) underwent examination with the FLASH sequence. Nine participants (median age, 37 years [IQR, 34-42 years; range, 25-62 years]; five men) underwent examination with the MP2RAGE sequence. A susceptibility difference between the expected location of the granular and molecular cerebellar layers was visually detected in the FLASH data in all participants. The segmentations derived from the whole-cerebellum MP2RAGE sequence showed the characteristic anatomic features of the cerebellum, like the transverse fissures and splitting folds. The cortical surface area (median, 949 cm2 [IQR, 825-1021 cm2]) was 1.8 times larger, and the cortical thickness (median, 0.88 mm [IQR, 0.81-0.93 mm]) was five times thinner than previous in vivo estimates and closer to ex vivo reference data. Conclusion In vivo imaging of the cerebellar cortical layers and surface and derivation of quantitative measures was feasible in a clinically acceptable acquisition time with use of motion-corrected 7.0-T MRI. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Dietrich in this issue.

Improved Selectivity in 7 T Digit Mapping Using VASO-CBV.

Functional magnetic resonance imaging (fMRI) at Ultra-high field (UHF, ≥ 7 T) benefits from significant gains in the BOLD contrast-to-noise ratio (CNR) and temporal signal-to-noise ratio (tSNR) compared to conventional field strengths (3 T). Although these improvements enabled researchers to study the human brain to unprecedented spatial resolution, the blood pooling effect reduces the spatial specificity of the widely-used gradient-echo BOLD acquisitions. In this context, vascular space occupancy (VASO-CBV) imaging may be advantageous since it is proposed to have a higher spatial specificity than BOLD. We hypothesized that the assumed higher specificity of VASO-CBV imaging would translate to reduced overlap in fine-scale digit representation maps compared to BOLD-based digit maps. We used sub-millimeter resolution VASO fMRI at 7 T to map VASO-CBV and BOLD responses simultaneously in the motor and somatosensory cortices during individual finger movement tasks. We assessed the cortical overlap in different ways, first by calculating similarity coefficient metrics (DICE and Jaccard) and second by calculating selectivity measures. In addition, we demonstrate a consistent topographical organization of the targeted digit representations (thumb-index-little finger) in the motor areas. We show that the VASO-CBV responses yielded less overlap between the digit clusters than BOLD, and other selectivity measures were higher for VASO-CBV too. In summary, these results were consistent across metrics and participants, confirming the higher spatial specificity of VASO-CBV compared to BOLD.

Towards functional spin-echo BOLD line-scanning in humans at 7T.

OBJECTIVE: Neurons cluster into sub-millimeter spatial structures and neural activity occurs at millisecond resolutions; hence, ultimately, high spatial and high temporal resolutions are required for functional MRI. In this work, we implemented a spin-echo line-scanning (SELINE) sequence to use in high spatial and temporal resolution fMRI. MATERIALS AND METHODS: A line is formed by simply rotating the spin-echo refocusing gradient to a plane perpendicular to the excited slice and by removing the phase-encoding gradient. This technique promises a combination of high spatial and temporal resolution (250 µm, 500 ms) and microvascular specificity of functional responses. We compared SELINE data to a corresponding gradient-echo version (GELINE). RESULTS: We demonstrate that SELINE showed much-improved line selection (i.e. a sharper line profile) compared to GELINE, albeit at the cost of a significant drop in functional sensitivity. DISCUSSION: This low functional sensitivity needs to be addressed before SELINE can be applied for neuroscientific purposes.

Auditory timing-tuned neural responses in the human auditory cortices.

Perception of sub-second auditory event timing supports multisensory integration, and speech and music perception and production. Neural populations tuned for the timing (duration and rate) of visual events were recently described in several human extrastriate visual areas. Here we ask whether the brain also contains neural populations tuned for auditory event timing, and whether these are shared with visual timing. Using 7T fMRI, we measured responses to white noise bursts of changing duration and rate. We analyzed these responses using neural response models describing different parametric relationships between event timing and neural response amplitude. This revealed auditory timing-tuned responses in the primary auditory cortex, and auditory association areas of the belt, parabelt and premotor cortex. While these areas also showed tonotopic tuning for auditory pitch, pitch and timing preferences were not consistently correlated. Auditory timing-tuned response functions differed between these areas, though without clear hierarchical integration of responses. The similarity of auditory and visual timing tuned responses, together with the lack of overlap between the areas showing these responses for each modality, suggests modality-specific responses to event timing are computed similarly but from different sensory inputs, and then transformed differently to suit the needs of each modality.

Comparing BOLD and VASO-CBV population receptive field estimates in human visual cortex.

Vascular Space Occupancy (VASO) is an alternative fMRI approach based on changes in Cerebral Blood Volume (CBV). VASO-CBV fMRI can provide higher spatial specificity than the blood oxygenation level-dependent (BOLD) method because the CBV response is thought to be limited to smaller vessels. To investigate how this technique compares to BOLD fMRI for cognitive neuroscience applications, we compared population receptive field (pRF) mapping estimates between BOLD and VASO-CBV. We hypothesized that VASO-CBV would elicit distinct pRF properties compared to BOLD. Specifically, since pRF size estimates also depend on vascular sources, we hypothesized that reduced vascular blurring might yield narrower pRFs for VASO-CBV measurements. We used a VASO sequence with a double readout 3D EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the visual cortex while participants viewed conventional pRF mapping stimuli. Both VASO-CBV and BOLD images show similar eccentricity and polar angle maps across all participants. Compared to BOLD-based measurements, VASO-CBV yielded lower tSNR and variance explained. The pRF size changed with eccentricity similarly for VASO-CBV and BOLD, and the pRF size estimates were similar for VASO-CBV and BOLD, even when we equate variance explained between VASO-CBV and BOLD. This result suggests that the vascular component of the pRF size is not dominating in either VASO-CBV or BOLD.

Functional magnetic resonance imaging responses during perceptual decision-making at 3 and 7 T in human cortex, striatum, and brainstem.

While functional magnetic resonance imaging (fMRI) at ultra-high field (7 T) promises a general increase in sensitivity compared to lower field strengths, the benefits may be most pronounced for specific applications. The current study aimed to evaluate the relative benefit of 7 over 3 T fMRI for the assessment of responses evoked in different brain regions by a well-controlled cognitive task. At 3 and 7 T, the same participants made challenging perceptual decisions about visual motion combined with monetary rewards for correct choices. Previous work on this task has extensively characterized the underlying cognitive computations and single-cell responses in cortical and subcortical structures. We quantified the evoked fMRI responses in extrastriate visual cortical areas, the striatum, and the brainstem during the decision interval and the post-feedback interval of the task. The dependence of response amplitudes on field strength during the decision interval differed between cortical, striatal, and brainstem regions, with a generally bigger 7 versus 3 T benefit in subcortical structures. We also found stronger responses during relatively easier than harder decisions at 7 T for dopaminergic midbrain nuclei, in line with reward expectation. Our results demonstrate the potential of 7 T fMRI for illuminating the contribution of small brainstem nuclei to the orchestration of cognitive computations in the human brain.

Chronotopic maps in human supplementary motor area.

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultrahigh-field 7-Tesla (7T) functional magnetic resonance imaging (fMRI), we show that in the medial premotor cortex (supplementary motor area [SMA]) of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface so as to form chronomaps. The response of each portion in a chronomap is enhanced by neighboring durations and suppressed by nonpreferred durations represented in distant portions of the map. These findings suggest duration-sensitive tuning as a possible neural mechanism underlying the recognition of time and demonstrate, for the first time, that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.

Ultra-high field fMRI reveals origins of feedforward and feedback activity within laminae of human ocular dominance columns.

Ultra-high field MRI can functionally image the cerebral cortex of human subjects at the submillimeter scale of cortical columns and laminae. Here, we investigate both in concert, by imaging ocular dominance columns (ODCs) in primary visual cortex (V1) across different cortical depths. We ensured that putative ODC patterns in V1 (a) are stable across runs, sessions, and scanners located in different continents, (b) have a width (~1.3 mm) expected from post-mortem and animal work and (c) are absent at the retinotopic location of the blind spot. We then dissociated the effects of bottom-up thalamo-cortical input and attentional feedback processes on activity in V1 across cortical depth. Importantly, the separation of bottom-up information flows into ODCs allowed us to validly compare attentional conditions while keeping the stimulus identical throughout the experiment. We find that, when correcting for draining vein effects and using both model-based and model-free approaches, the effect of monocular stimulation is largest at deep and middle cortical depths. Conversely, spatial attention influences BOLD activity exclusively near the pial surface. Our findings show that simultaneous interrogation of columnar and laminar dimensions of the cortical fold can dissociate thalamocortical inputs from top-down processing, and allow the investigation of their interactions without any stimulus manipulation.

Individualized cognitive neuroscience needs 7T: Comparing numerosity maps at 3T and 7T MRI.

The field of cognitive neuroscience is weighing evidence about whether to move from the current standard field strength of 3 Tesla (3T) to ultra-high field (UHF) of 7T and above. The present study contributes to the evidence by comparing a computational cognitive neuroscience paradigm at 3T and 7T. The goal was to evaluate the practical effects, i.e. model predictive power, of field strength on a numerosity task using accessible pre-processing and analysis tools. Previously, using 7T functional magnetic resonance imaging and biologically-inspired analyses, i.e. population receptive field modelling, we discovered topographical organization of numerosity-selective neural populations in human parietal cortex. Here we show that these topographic maps are also detectable at 3T. However, averaging of many more functional runs was required at 3T to reliably reconstruct numerosity maps. On average, one 7T run had about four times the model predictive power of one 3T run. We believe that this amount of scanning would have made the initial discovery of the numerosity maps on 3T highly infeasible in practice. Therefore, we suggest that the higher signal-to-noise ratio and signal sensitivity of UHF MRI is necessary to build mechanistic models of the organization and function of our cognitive abilities in individual participants.

Can 7T MPRAGE match MP2RAGE for gray-white matter contrast?

Ultra-High Field (UHF) MRI provides a significant increase in Signal-to-Noise Ratio (SNR) and gains in contrast weighting in several functional and structural acquisitions. Unfortunately, an increase in field strength also induces non-uniformities in the transmit field (B1+) that can compromise image contrast non-uniformly. The MPRAGE is one of the most common T1 weighted (T1w) image acquisitions for structural imaging. It provides excellent contrast between gray and white matter and is widely used for brain segmentation. At 7T, the signal non-uniformities tend to complicate this and therefore, the self-bias-field corrected MP2RAGE is often used there. In both MPRAGE and MP2RAGE, more homogeneous image contrast can be achieved with adiabatic pulses, like the TR-FOCI inversion pulse, or special pulse design on parallel transmission systems, like Universal Pulses (UP). In the present study, we investigate different strategies to improve the bias-field for MPRAGE at 7T, comparing the contrast and GM/WM segmentability against MP2RAGE. The higher temporal efficiency of MPRAGE combined with the potential of the user-friendly UPs was the primary motivation for this MPRAGE-MP2RAGE comparison. We acquired MPRAGE data in six volunteers, adding a k-space shutter to reduce scan time, a kt-point UP approach for homogeneous signal excitation, and a TR-FOCI pulse for homogeneous inversion. Our results show remarkable signal contrast improvement throughout the brain, including regions of low B1+ such as the cerebellum. The improvements in the MPRAGE were largest following the introduction of the UPs. In addition to the CNR, both SNR and GM/WM segmentability were also assessed. Among the MPRAGEs, the combined strategy (UP + TR-FOCI) yielded highest SNR and showed highest spatial similarity between GM segments to the MP2RAGE. Interestingly, the distance between gray and white matter peaks in the intensity histograms did not increase, as better pulses and higher SNR especially benefitted the (cerebellar) gray matter. Overall, the gray-white matter contrast from MP2RAGE is higher, with higher CNR and higher intensity peak distances, even when scaled to scan time. Hence, the extra acquisition time for MP2RAGE is justified by the improved segmentability.

Comparing hand movement rate dependence of cerebral blood volume and BOLD responses at 7T.

Functional magnetic resonance imaging (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast takes advantage of the coupling between neuronal activity and the hemodynamics to allow a non-invasive localisation of the neuronal activity. In general, fMRI experiments assume a linear relationship between neuronal activation and the observed hemodynamics. However, the relationship between BOLD responses, neuronal activity, and behaviour are often nonlinear. In addition, the nonlinearity between BOLD responses and behaviour may be related to neuronal process rather than a neurovascular uncoupling. Further, part of the nonlinearity may be driven by vascular nonlinearity effects in particular from large vessel contributions. fMRI based on cerebral blood volume (CBV), promises a higher microvascular specificity, potentially without vascular nonlinearity effects and reduced contamination of the large draining vessels compared to BOLD. In this study, we aimed to investigate differences in BOLD and VASO-CBV signal changes during a hand movement task over a broad range of movement rates. We used a double readout 3D-EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the sensorimotor cortex. The measured BOLD and VASO-CBV responses increased very similarly in a nonlinear fashion, plateauing for movement rates larger than 1 Hz. Our findings show a tight relationship between BOLD and VASO-CBV responses, indicating that the overall interplay of CBV and BOLD responses are similar for the assessed range of movement rates. These results suggest that the observed nonlinearity of neuronal origin is already present in VASO-CBV measurements, and consequently shows relatively unchanged BOLD responses.

Advances in resting state fMRI acquisitions for functional connectomics.

Resting state functional magnetic resonance imaging (rs-fMRI) is based on spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal, which occur simultaneously in different brain regions, without the subject performing an explicit task. The low-frequency oscillations of the rs-fMRI signal demonstrate an intrinsic spatiotemporal organization in the brain (brain networks) that may relate to the underlying neural activity. In this review article, we briefly describe the current acquisition techniques for rs-fMRI data, from the most common approaches for resting state acquisition strategies, to more recent investigations with dedicated hardware and ultra-high fields. Specific sequences that allow very fast acquisitions, or multiple echoes, are discussed next. We then consider how acquisition methods weighted towards specific parts of the BOLD signal, like the Cerebral Blood Flow (CBF) or Volume (CBV), can provide more spatially specific network information. These approaches are being developed alongside the commonly used BOLD-weighted acquisitions. Finally, specific applications of rs-fMRI to challenging regions such as the laminae in the neocortex, and the networks within the large areas of subcortical white matter regions are discussed. We finish the review with recommendations for acquisition strategies for a range of typical applications of resting state fMRI.

Relation between palm and finger cortical representations in primary somatosensory cortex: A 7T fMRI study.

Many studies focused on the cortical representations of fingers, while the palm is relatively neglected despite its importance for hand function. Here, we investigated palm representation (PR) and its relationship with finger representations (FRs) in primary somatosensory cortex (S1). Few studies in humans suggested that PR is located medially with respect to FRs in S1, yet to date, no study directly quantified the somatotopic organization of PR and the five FRs. Importantly, the link between the somatotopic organization of PR and FRs and their activation properties remains largely unexplored. Using 7T fMRI, we mapped PR and the five FRs at the single subject level. First, we analyzed the cortical distance between PR and FRs to determine their somatotopic organization. Results show that PR was located medially with respect to D5. Second, we tested whether the observed cortical distances would predict the relationship between PR and FRs activations. Using three complementary measures (cross-activations, pattern similarity and resting-state connectivity), we show that the relationship between PR and FRs activations were not determined by their somatotopic organization, that is, there was no gradient moving from D5 to D1, except for resting-state connectivity, which was predicted by the somatotopy. Instead, we show that the representational geometry of PR and FRs activations reflected the physical structure of the hand. Collectively, our findings suggest that the spatial proximity between topographically organized neuronal populations do not necessarily predicts their functional properties, rather the structure of the sensory space (e.g., the hand shape) better describes the observed results.

QSM reconstruction challenge 2.0: A realistic in silico head phantom for MRI data simulation and evaluation of susceptibility mapping procedures.

PURPOSE: To create a realistic in silico head phantom for the second QSM reconstruction challenge and for future evaluations of processing algorithms for QSM. METHODS: We created a digital whole-head tissue property phantom by segmenting and postprocessing high-resolution (0.64 mm isotropic), multiparametric MRI data acquired at 7 T from a healthy volunteer. We simulated the steady-state magnetization at 7 T using a Bloch simulator and mimicked a Cartesian sampling scheme through Fourier-based processing. Computer code for generating the phantom and performing the MR simulation was designed to facilitate flexible modifications of the phantom in the future, such as the inclusion of pathologies as well as the simulation of a wide range of acquisition protocols. Specifically, the following parameters and effects were implemented: TR and TE, voxel size, background fields, and RF phase biases. Diffusion-weighted imaging phantom data are provided, allowing future investigations of tissue-microstructure effects in phase and QSM algorithms. RESULTS: The brain part of the phantom featured realistic morphology with spatial variations in relaxation and susceptibility values similar to the in vivo setting. We demonstrated some of the phantom's properties, including the possibility of generating phase data with nonlinear evolution over TE due to partial-volume effects or complex distributions of frequency shifts within the voxel. CONCLUSION: The presented phantom and computer programs are publicly available and may serve as a ground truth in future assessments of the faithfulness of quantitative susceptibility reconstruction algorithms.

A local multi-transmit coil combined with a high-density receive array for cerebellar fMRI at 7 T.

The human cerebellum is involved in a wide array of functions, ranging from motor control to cognitive control, and as such is of great neuroscientific interest. However, its function is underexplored in vivo, due to its small size, its dense structure and its placement at the bottom of the brain, where transmit and receive fields are suboptimal. In this study, we combined two dense coil arrays of 16 small surface receive elements each with a transmit array of three antenna elements to improve BOLD sensitivity in the human cerebellum at 7 T. Our results showed improved B1+ and SNR close to the surface as well as g-factor gains compared with a commercial coil designed for whole-head imaging. This resulted in improved signal stability and large gains in the spatial extent of the activation close to the surface (<3.5 cm), while good performance was retained deeper in the cerebellum. Modulating the phase of the transmit elements of the head coil to constructively interfere in the cerebellum improved the B1+ , resulting in a temporal SNR gain. Overall, our results show that a dedicated transmit array along with the SNR gains of surface coil arrays can improve cerebellar imaging, at the cost of a decreased field of view and increased signal inhomogeneity.

Whole-body somatotopic maps in the cerebellum revealed with 7T fMRI.

The cerebellum is known to contain a double somatotopic body representation. While the anterior lobe body map has shown a robust somatotopic organization in previous fMRI studies, the representations in the posterior lobe have been more difficult to observe and are less precisely characterized. In this study, participants went through a simple motor task asking them to move either the eyes (left-right guided saccades), tongue (left-right movement), thumbs, little fingers or toes (flexion). Using high spatial resolution fMRI data acquired at ultra-high field (7T), with special care taken to obtain sufficient B1 over the entire cerebellum and a cerebellar surface reconstruction facilitating visual inspection of the results, we were able to precisely map the somatotopic representations of these five distal body parts on both subject- and group-specific cerebellar surfaces. The anterior lobe (including lobule VI) showed a consistent and robust somatotopic gradient. Although less robust, the presence of such a gradient in the posterior lobe, from Crus II to lobule VIIIb, was also observed. Additionally, the eyes were also strongly represented in Crus I and the oculomotor vermis. Overall, crosstalk between the different body part representations was negligible. Taken together, these results show that multiple representations of distal body parts are present in the cerebellum, across many lobules, and they are organized in an orderly manner.

fMRI protocol optimization for simultaneously studying small subcortical and cortical areas at 7 ​T.

Most fundamental cognitive processes rely on brain networks that include both cortical and subcortical structures. Studying such networks using functional magnetic resonance imaging (fMRI) requires a data acquisition protocol that provides blood-oxygenation-level dependent (BOLD) sensitivity across the entire brain. However, when using standard single echo, echo planar imaging protocols, researchers face a tradeoff between BOLD-sensitivity in cortex and in subcortical areas. Multi echo protocols avoid this tradeoff and can be used to optimize BOLD-sensitivity across the entire brain, at the cost of an increased repetition time. Here, we empirically compare the BOLD-sensitivity of a single echo protocol to a multi echo protocol. Both protocols were designed to meet the specific requirements for studying small, iron rich subcortical structures (including a relatively high spatial resolution and short echo times), while retaining coverage and BOLD-sensitivity in cortical areas. The results indicate that both sequences lead to similar BOLD-sensitivity across the brain at 7 â€‹T.

Sharpness in motion corrected quantitative imaging at 7T.

Sub-millimeter imaging at 7T has opened new possibilities for qualitatively and quantitatively studying brain structure as it evolves throughout the life span. However, subject motion introduces image blurring on the order of magnitude of the spatial resolution and is thus detrimental to image quality. Such motion can be corrected for, but widespread application has not yet been achieved and quantitative evaluation is lacking. This raises a need to quantitatively measure image sharpness throughout the brain. We propose a method to quantify sharpness of brain structures at sub-voxel resolution, and use it to assess to what extent limited motion is related to image sharpness. The method was evaluated in a cohort of 24 healthy volunteers with a wide and uniform age range, aiming to arrive at results that largely generalize to larger populations. Using 3D fat-excited motion navigators, quantitative R1, R2* and Quantitative Susceptibility Maps and T1-weighted images were retrospectively corrected for motion. Sharpness was quantified in all modalities for selected regions of interest (ROI) by fitting the sigmoidally shaped error function to data within locally homogeneous clusters. A strong, almost linear correlation between motion and sharpness improvement was observed, and motion correction significantly improved sharpness. Overall, the Full Width at Half Maximum reduced from 0.88 mm to 0.70 mm after motion correction, equivalent to a 2.0 times smaller voxel volume. Motion and sharpness were not found to correlate with the age of study participants. We conclude that in our data, motion correction using fat navigators is overall able to restore the measured sharpness to the imaging resolution, irrespective of the amount of motion observed during scanning.