Abstract Human hand coordination exceeds that of other species, including great apes, and is marked by pronounced right-hand dominance. This specialization parallels an expansion of its cortical representation, forming the hand-knob in the motor cortex. In humans, this region shows high myelination on quantitative MRI (qMRI), but whether this feature is shared with great apes remains unclear. It is also unknown whether increased right-hand dominance in humans is mirrored by greater hemispheric asymmetry in cortical microstructure. Using high-resolution qMRI, we compared motor cortex subdivisions controlling the leg, hand, and face in humans and chimpanzees. We found consistently higher myelin and iron content in the hand-knob in both species, suggesting an evolutionarily conserved role. However, only humans showed enhanced rightward lateralization. These results highlight both conserved and species-specific features of the motor cortex, offering insights into the evolution of manual dexterity and handedness.

PurposeTo compare MR axon radius estimation in human white matter using a multiband spiral sequence combined with field monitoring to the current state-of-the-art echo-planar imaging (EPI)-based approach.MethodsA custom multiband spiral sequence was used for diffusion-weighted imaging at ultra-high b$$ b $$-values. Field monitoring and higher order image reconstruction were employed to greatly reduce artifacts in spiral images. Diffusion weighting parameters were chosen to match a state-of-the art EPI-based axon radius mapping protocol. The spiral approach was compared to the EPI approach by comparing the image signal-to-noise ratio (SNR) and performing a test-retest study to assess the respective variability and repeatability of axon radius mapping. Effective axon radius estimates were compared over white matter voxels and along the left corticospinal tract.ResultsIncreased SNR and reduced artifacts in spiral images led to reduced variability in resulting axon radius maps, especially in low-SNR regions. Test-retest variability was reduced by a factor of approximately 1.5 using the spiral approach. Reduced repeatability due to significant bias was found for some subjects in both spiral and EPI approaches, and attributed to scanner instability, pointing to a previously unknown limitation of the state-of-the-art approach.ConclusionCombining spiral readouts with field monitoring improved mapping of the effective axon radius compared to the conventional EPI approach.

Short association fibres (SAF) are the most abundant fibre pathways in the human white matter. Until recently, SAF could not be mapped comprehensively in vivo because diffusion weighted magnetic resonance imaging with sufficiently high spatial resolution needed to map these thin and short pathways was not possible. Recent developments in acquisition hardware and sequences allowed us to create a dedicated in vivo method for mapping the SAF based on sub-millimetre spatial resolution diffusion weighted tractography, which we validated in the human primary (V1) and secondary (V2) visual cortex against the expected SAF retinotopic order. Here, we extended our original study to assess the feasibility of the method to map SAF in higher cortical areas by including SAF up to V3. Our results reproduced the expected retinotopic order of SAF in the V2-V3 and V1-V3 stream, demonstrating greater robustness to the shorter V1-V2 and V2-V3 than the longer V1-V3 connections. The demonstrated ability of the method to map higher-order SAF connectivity patterns in vivo is an important step towards its application across the brain.

The extraordinary number of short association fibres (SAF) connecting neighbouring cortical areas is a prominent feature of the large gyrified human brain. The contribution of SAF to the human connectome is largely unknown because of methodological challenges in mapping them. We present a method to characterise cortico–cortical connectivity mediated by SAF in topologically organised cortical areas. We introduce the ‘structural connective fields’ (sCF) metric which specifically quantifies neuronal signal propagation and integration mediated by SAF. This new metric complements functional connective field metrics integrating across contributions from short- and long-range white matter and intracortical fibres. Applying the method in the human early visual processing stream, we show that SAF preserve cortical functional topology. Retinotopic maps of V2 and V3 could be predicted from retinotopy in V1 and SAF connectivity. The sCF sizes increased along the cortical hierarchy and were smaller than their functional counterparts, in line with the latter being additionally broadened by long-range and intracortical connections. In vivo sCF mapping provides insights into short-range cortico– cortical connectivity in humans comparable to tract tracing studies in animal research and is an essential step towards creating a complete human connectome. Highlights ### Competing Interest Statement The Max Planck Institute for Human Cognitive and Brain Sciences and Wellcome Centre for Human Neuroimaging have institutional research agreements with Siemens Healthcare. NW holds a patent on acquisition of MRI data during spoiler gradients (US 10,401,453 B2). NW was a speaker at an event organised by Siemens Healthcare and was reimbursed for the travel expenses.

Chimpanzee brain maturation provides an invaluable framework for understanding the evolution of the human brain. We performed ultra-high resolution quantitative magnetic resonance imaging (qMRI) with histological validation on post mortem brains from captive and wild chimpanzees with a broad age range. We mapped developmental myelination and age-related iron accumulation across regions and layers of the neocortex. Compared to humans, chimpanzees showed more myelination and iron deposition in motor and premotor cortices, while the auditory cortex was more strongly myelinated in humans. Our model suggests that chimpanzees' cortical myelination was largely completed by the age of nine years, while iron accumulation continued throughout the lifespan. The regions with highest adult levels of myelin and iron took the longest to mature, challenging the widespread assumption that highly myelinated regions complete their development first. The reported maps and developmental curves provide a foundation for comparative neuroscience research and understanding of human brain evolution. ### Competing Interest Statement The Max Planck Institute for Human Cognitive and Brain Sciences has an institutional research agreement with Siemens Healthcare. Nikolaus Weiskopf holds a patent on acquisition of MRI data during spoiler gradients (US 10401453 B2). Nikolaus Weiskopf was a speaker at an event organized by Siemens Healthcare and was reimbursed for the travel expenses.

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (${R_{1}}$), effective transverse relaxation rate (${R_{2}}^{\ast }$), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (${R_{2}}^{\ast }$ at 3T, ${R_{1}}$ at 7T), endothelial cells (${R_{1}}$ and MTsat at 3T), microglia (${R_{1}}$ and MTsat at 3T, ${R_{1}}$ at 7T), and oligodendrocytes and oligodendrocyte precursor cells (${R_{1}}$ at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.

Cortical grey matter (CGM) and superficial white matter (SWM) undergo pathological changes, but standard MRI spatial resolutions make interpreting disease-related effects at their interface challenging. We present findings from a study investigating the grey/white interface in typical amnestic Alzheimer’s disease (tAD), posterior cortical atrophy (PCA) and healthy controls using ultra-high-resolution quantitative MRI measures sensitive to microstructural properties. Eleven participants (Table 1) were scanned at 7T using multi-echo FLASH (0.5mm isotropic resolution with prospective motion correction) and diffusion MRI (dMRI) (1.25mm isotropic resolution). The hMRI toolbox produced multi-parametric mapping (MPM) measures: R1, R2* and Proton Density (PD) (Vaculciakova et al., 2021https://doi.org/10.1002/mrm.29253). dMRI processing included denoising and correcting for Gibbs ringing, eddy currents, susceptibility artifacts and motion. Metrics from dMRI were fractional anisotropy (FA), and mean diffusivity (MD), as well as tissue fraction (TF), neurite density index (NDI) and orientation dispersion index (ODI) from Neurite Orientation Dispersion and Density Imaging (NODDI). A deep learning segmentation approach estimated the grey/white boundary (Billot et al., 2021, arXiv:2107.09559). MPM and dMRI measures were sampled from the CGM into the SWM at 0.5mm increments in regions of interest (Harvard-Oxford cortical atlas). Tissue-weighted (tw) averages were calculated for NDI and ODI. Metrics were visualized across the grey/white interface using boxplots. Figures 1-2 show MPM and dMRI measures in the precuneus (dashed lines indicate group medians). Qualitatively, most tAD and PCA participants had lower R1 and R2* than controls, most prominently 0.5mm into the SWM (Figure 1). PD appeared higher in tAD and PCA patients across the grey/white interface. Qualitatively, most tAD and PCA participants had lower TF and higher MD in the CGM, where twNDI and FA appeared lower than controls across grey/white interface (Figure 2). Most tAD and PCA had qualitatively lower twODI in CGM and a flatter slope across the grey/white interface compared to controls. Macromolecular (R1, R2* and twNDI) and iron content (R2*) MR measures at 7T appear reduced in tAD and PCA across the grey/white interface, whereas neurite organisational complexity (twODI) may become more homogeneous. Ongoing study will assess if these findings are consistent with further participants.

The selection pressures that drove dramatic encephalisation processes through the mammal lineage remain elusive, as does knowledge of brain structure reorganisation through this process. In particular, considerable structural brain changes are present across the primate lineage, culminating in the complex human brain that allows for unique behaviours such as language and sophisticated tool use. To understand this evolution, a diverse sample set of humans' closest relatives with varying socio‐ecologies is needed. However, current brain banks predominantly curate brains from primates that died in zoological gardens. We try to address this gap by establishing a field pipeline mitigating the challenges associated with brain extractions of wild primates in their natural habitat. The success of our approach is demonstrated by our ability to acquire a novel brain sample of deceased primates with highly variable socio‐ecological exposure and a particular focus on wild chimpanzees. Methods in acquiring brain tissue from wild settings are comprehensively explained, highlighting the feasibility of conducting brain extraction procedures under strict biosafety measures by trained veterinarians in field sites. Brains are assessed at a fine‐structural level via high‐resolution MRI and state‐of‐the‐art histology. Analyses confirm that excellent tissue quality of primate brains sourced in the field can be achieved with a comparable tissue quality of brains acquired from zoo‐living primates. Our field methods are noninvasive, here defined as not harming living animals, and may be applied to other mammal systems than primates. In sum, the field protocol and methodological pipeline validated here pose a major advance for assessing the influence of socio‐ecology on medium to large mammal brains, at both macro‐ and microstructural levels as well as aiding with the functional annotation of brain regions and neuronal pathways via specific behaviour assessments.

The characterization of cortical myelination is essential for the study of structure-function relationships in the human brain. However, knowledge about cortical myelination is largely based on post-mortem histology, which generally renders direct comparison to function impossible. The repeating pattern of pale-thin-pale-thick stripes of cytochrome oxidase (CO) activity in the primate secondary visual cortex (V2) is a prominent columnar system, in which histology also indicates different myelination of thin/thick versus pale stripes. We used quantitative magnetic resonance imaging (qMRI) in conjunction with functional magnetic resonance imaging (fMRI) at ultra-high field strength (7 T) to localize and study myelination of stripes in four human participants at sub-millimeter resolution in vivo. Thin and thick stripes were functionally localized by exploiting their sensitivity to color and binocular disparity, respectively. Resulting functional activation maps showed robust stripe patterns in V2 which enabled further comparison of quantitative relaxation parameters between stripe types. Thereby, we found lower longitudinal relaxation rates (R-1) of thin and thick stripes compared to surrounding gray matter in the order of 1-2%, indicating higher myelination of pale stripes. No consistent differences were found for effective transverse relaxation rates (R-2*). The study demonstrates the feasibility to investigate structure-function relationships in living humans within one cortical area at the level of columnar systems using qMRI.

PurposeMagnetization transfer saturation () is a useful marker to probe tissue macromolecular content and myelination in the brain. The increased ‐inhomogeneity at T and significantly larger saturation pulse flip angles which are often used for postmortem studies exceed the limits where previous correction methods are applicable. Here, we develop a calibration‐based correction model and procedure, and validate and evaluate it in postmortem 7T data of whole chimpanzee brains.TheoryThe dependence of was investigated by varying the off‐resonance saturation pulse flip angle. For the range of saturation pulse flip angles applied in typical experiments on postmortem tissue, the dependence was close to linear. A linear model with a single calibration constant is proposed to correct bias in by mapping it to the reference value of the saturation pulse flip angle.Methods was estimated voxel‐wise in five postmortem chimpanzee brains. “Individual‐based global parameters” were obtained by calculating the mean within individual specimen brains and “group‐based global parameters” by calculating the means of the individual‐based global parameters across the five brains.ResultsThe linear calibration model described the data well, though was not entirely independent of the underlying tissue and . Individual‐based correction parameters and a group‐based global correction parameter () led to visible, quantifiable reductions of ‐biases in high‐resolution maps.ConclusionThe presented model and calibration approach effectively corrects for inhomogeneities in postmortem 7T data.

PURPOSE:High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients. METHODS:Camera-based optical prospective motion correction (PMC) and FID navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics. RESULTS:NAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs. 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections. CONCLUSION:Navigator correction and PMC significantly improved the quality of PD, R1, and R2* maps, particularly in less compliant elderly volunteers and dementia patients.

Multi-Parameter Mapping (MPM) is a comprehensive quantitative neuroimaging protocol that enables estimation of four physical parameters (longitudinal and effective transverse relaxation rates R1 and R2*, proton density PD, and magnetization transfer saturation MTsat) that are sensitive to microstructural tissue properties such as iron and myelin content. Their capability to reveal microstructural brain differences, however, is tightly bound to controlling random noise and artefacts (e.g. caused by head motion) in the signal. Here, we introduced a method to estimate the local error of PD, R1, and MTsat maps that captures both noise and artefacts on a routine basis without requiring additional data. To investigate the method's sensitivity to random noise, we calculated the model-based signal-to-noise ratio (mSNR) and showed in measurements and simulations that it correlated linearly with an experimental raw-image-based SNR map. We found that the mSNR varied with MPM protocols, magnetic field strength (3T vs. 7T) and MPM parameters: it halved from PD to R1 and decreased from PD to MTsat by a factor of 3-4. Exploring the artefact-sensitivity of the error maps, we generated robust MPM parameters using two successive acquisitions of each contrast and the acquisition-specific errors to down-weight erroneous regions. The resulting robust MPM parameters showed reduced variability at the group level as compared to their single-repeat or averaged counterparts. The error and mSNR maps may better inform power-calculations by accounting for local data quality variations across measurements. Code to compute the mSNR maps and robustly combined MPM maps is available in the open-source hMRI toolbox.

The noninvasive quantification of axonal morphology is an exciting avenue for gaining understanding of the function and structure of the central nervous system. Accurate non‐invasive mapping of micron‐sized axon radii using commonly applied neuroimaging techniques, that is, diffusion‐weighted MRI, has been bolstered by recent hardware developments, specifically MR gradient design. Here the whole brain characterization of the effective MR axon radius is presented and the inter‐ and intra‐scanner test–retest repeatability and reproducibility are evaluated to promote the further development of the effective MR axon radius as a neuroimaging biomarker. A coefficient‐of‐variability of approximately 10% in the voxelwise estimation of the effective MR radius is observed in the test–retest analysis, but it is shown that the performance can be improved fourfold using a customized along‐tract analysis.

Quantitative magnetic resonance imaging (qMRI) goes beyond conventional MRI, which aims primarily at local image contrast. It provides specific physical parameters related to the nuclear spin of protons in water, such as relaxation times. These parameters carry information about the local microstructural environment of the protons (such as myelin in the brain). Non-invasive in vivo histology using MRI (hMRI) aims to use this information to directly characterize biological tissue microstructure, partially replacing or complementing classical invasive histology. The understanding of MRI tissue contrast provided by hMRI is, in turn, crucial for further improvements of qMRI, and they should be considered closely interlinked. We discuss concepts, models and validation approaches, pointing out challenges and the latest advances in this field. Further, we point out links to physics, including computational and analytical approaches and developments in materials science and photonics, that aid in reference data acquisition and model validation. Quantitative magnetic resonance imaging and in vivo histology go beyond standard magnetic resonance imaging, aiming at characterizing tissue microstructure of the living brain. This Technical Review discusses advances in concepts, instrumentation, biophysical models and validation approaches facilitating this rapidly developing field.