The mesoscopic organization of the human neocortex is of great interest for cognitive neuroscience. However, fMRI in humans typically maps the functional units of cognitive processing on a macroscopic level. With the advent of ultra-high field MRI (≥7T), it has become possible to acquire fMRI data with sub-millimetre resolution, enabling probing the laminar and columnar circuitry in humans. Currently, laminar BOLD responses are not directly observed but inferred via data analysis, due to coarse spatial resolution of fMRI (e.g. 0.7–0.8 mm isotropic) relative to the extent of histological laminae. In this study, we introduce a novel approach for mapping the cortical BOLD response at the spatial scale of cortical layers and columns at 7T (an unprecedented 0.1 mm, either in the laminar or columnar direction). We demonstrate experimentally and using simulations, the superiority of the novel approach compared to standard approaches for human laminar fMRI in terms of effective spatial resolution in either laminar or columnar direction. In addition, we provide evidence that the laminar BOLD signal profile is not homogeneous even over short patches of cortex. In summary, the proposed novel approach affords the ability to directly study the mesoscopic organization of the human cortex, thus, bridging the gap between human cognitive neuroscience and invasive animal studies.

PurposeTo design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla.MethodsA 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic.ResultsThe transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was ∼ 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic.ConclusionThe 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T.

No abstract

Several magnetic resonance imaging (MRI) contrasts are sensitive to myelin content in gray matter in vivo which has ignited ambitions of MRI-based in vivo cortical histology. Ultra-high field (UHF) MRI, at fields of 7 T and beyond, is crucial to provide the resolution and contrast needed to sample contrasts over the depth of the cortex and get closer to layer resolved imaging. Ex vivo MRI of human post mortem samples is an important stepping stone to investigate MRI contrast in the cortex, validate it against histology techniques applied in situ to the same tissue, and investigate the resolutions needed to translate ex vivo findings to in vivo UHF MRI. Here, we investigate key technology to extend such UHF studies to large human brain samples while maintaining high resolution, which allows investigation of the layered architecture of several cortical areas over their entire 3D extent and their complete borders where architecture changes. A 16 channel cylindrical phased array radiofrequency (RF) receive coil was constructed to image a large post mortem occipital lobe sample (~80×80×80 mm3) in a wide-bore 9.4 T human scanner with the aim of achieving high-resolution anatomical and quantitative MR images. Compared with a human head coil at 9.4 T, the maximum Signal-to-Noise ratio (SNR) was increased by a factor of about five in the peripheral cortex. Although the transmit profile with a circularly polarized transmit mode at 9.4 T is relatively inhomogeneous over the large sample, this challenge was successfully resolved with parallel transmit using the kT-points method. Using this setup, we achieved 60μm anatomical images for the entire occipital lobe showing increased spatial definition of cortical details compared to lower resolutions. In addition, we were able to achieve sufficient control over SNR, B0 and B1 homogeneity and multi-contrast sampling to perform quantitative T2* mapping over the same volume at 200 μm. Markov Chain Monte Carlo sampling provided maximum posterior estimates of quantitative T2* and their uncertainty, allowing delineation of the stria of Gennari over the entire length and width of the calcarine sulcus. We discuss how custom RF receive coil arrays built to specific large post mortem sample sizes can provide a platform for UHF cortical layer-specific quantitative MRI over large fields of view.

The ability to image human tissue samples in 3D, with both cellular resolution and a large field of view (FOV), can improve fundamental and clinical investigations. Here, we demonstrate the feasibility of light-sheet imaging of ~5 cm3 sized formalin fixed human brain and up to ~7 cm3 sized formalin fixed paraffin embedded (FFPE) prostate cancer samples, processed with the FFPE-MASH protocol. We present a light-sheet microscopy prototype, the cleared-tissue dual view Selective Plane Illumination Microscope (ct-dSPIM), capable of fast 3D high-resolution acquisitions of cm3 scale cleared tissue. We used mosaic scans for fast 3D overviews of entire tissue samples or higher resolution overviews of large ROIs with various speeds: (a) Mosaic 16 (16.4 µm isotropic resolution, ~1.7 h/cm3), (b) Mosaic 4 (4.1 µm isotropic resolution, ~ 5 h/cm3) and (c) Mosaic 0.5 (0.5 µm near isotropic resolution, ~15.8 h/cm3). We could visualise cortical layers and neurons around the border of human brain areas V1&V2, and could demonstrate suitable imaging quality for Gleason score grading in thick prostate cancer samples. We show that ct-dSPIM imaging is an excellent technique to quantitatively assess entire MASH prepared large-scale human tissue samples in 3D, with considerable future clinical potential.

Motion signals can bias the perceived position of visual stimuli. While the apparent position of a stimulus is biased in the direction of motion, electro-physiological studies have shown that the receptive field (RF) of neurons is shifted in the direction opposite to motion, at least in cats and macaque monkeys. In humans, it remains unclear how motion signals affect population RF (pRF) estimates. We addressed this question using psychophysical measurements and functional magnetic resonance imaging (fMRI) at 7 Tesla. We systematically varied two factors: the motion direction of the carrier pattern (inward, outward and flicker motion) and the contrast of the mapping stimulus (low and high stimulus contrast). We observed that while physical positions were identical across all conditions, presence of low-contrast motion, but not high-contrast motion, shifted perceived stimulus position in the direction of motion. Correspondingly, we found that pRF estimates in early visual cortex were shifted against the direction of motion for low-contrast stimuli but not for high stimulus contrast. We offer an explanation in form of a model for why apertures are perceptually shifted in the direction of motion even though pRFs shift in the opposite direction.Keywords visual neuroscience · position perception · population receptive fields · visual field projections 1 IntroductionAn important task of the visual system is to infer the location of objects in our environment. A wide range of psychophysical studies shows that motion signals lead to systematic localisation biases [1,2,3,4,5,6,7,8,9]. In illusions called motion-induced position shifts (MIPS), a coherent motion signal shifts the apparent location of a stimulus [1]. For example, when drifting Gabor patches are presented within a stationary aperture, the stimulus appears shifted in the direction of motion [2,6,7]. Such illusions raise the question how our visual system encodes location and how, in the case of MIPS, the apparent position shift can be explained. Furthermore, they offer a dissociation between the physical and the perceived position of a stimulus that can clarify which neuronal processes correspond to the apparent position of the stimulus. MOTION DISPLACES POPULATION RECEPTIVE FIELDSThe magnitude of MIPS is known to depend on spatial and temporal properties of the stimulus. MIPS are larger when the stimulus is shown for longer duration (tested up to 453 ms; [6]), presented at higher speed [6,9] or at higher eccentricities [10,6,9]. The magnitude of MIPS furthermore depends on spatial blurring of the presented stimulus. Blurred stimulus edges lead to larger perceptual displacements than sharp edges [4,9] and increasing the size of the Gaussian envelope of a Gabor stimulus yields larger MIPS [4]. Arnold et al. [7] have suggested that MIPS are driven by modulation of apparent contrast of the stimulus. Supporting this suggestion, they reported perceived position shifts when observers were asked to match the extremities of two contrast envelopes (low-contrast region),...

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

No abstract