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To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.

Electroencephalography (EEG) is a technique for non-invasively measuring neuronal activity in the human brain using electrodes placed on the participant's scalp. With the advancement of digital technologies, EEG analysis has evolved over time from the qualitative analysis of amplitude and frequency modulations to a comprehensive analysis of the complex spatiotemporal characteristics of the recorded signals. EEG is now considered a powerful tool for measuring neural processes in the same time frame in which they happen (i.e. the subsecond range). However, it is commonly argued that EEG suffers from low spatial resolution, which makes it difficult to localize the generators of EEG activity accurately and reliably. Today, the availability of high-density EEG (hdEEG) systems, combined with methods for incorporating information on head anatomy and sophisticated source-localization algorithms, has transformed EEG into an important neuroimaging tool. hdEEG offers researchers and clinicians a rich and varied range of applications. It can be used not only for investigating neural correlates in motor and cognitive neuroscience experiments, but also for clinical diagnosis, particularly in the detection of epilepsy and the characterization of neural impairments in a wide range of neurological disorders. Notably, the integration of hdEEG systems with other physiological recordings, such as kinematic and/or electromyography data, might be especially beneficial to better understand the neuromuscular mechanisms associated with deconditioning in ageing and neuromotor disorders, by mapping the neurokinematic and neuromuscular connectivity patterns directly in the brain., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Abstract The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation‐free reconstruction. Here, the authors describe an integrated serial sectioning polarization‐sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label‐free multi‐contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high‐throughput reconstruction of 4 × 4 × 2cm3 sample blocks and simple registration between PSOCT and 2PM images that enable comprehensive analysis of myelin content, vascular structure, and cellular information. The high‐resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin‐filled cell bodies in the cortex and white matter. It is shown that the imaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future.

Molecular and functional imaging techniques have been used and combined with pharmacological probes to evaluate the role of dopamine in impulsivity. Overall, strong evidence links striatal dopaminergic function with impulsivity, measured by self-reports and laboratory tests of cognitive control and reward-based decision-making. The combination of molecular imaging using positron emission tomography (PET) with functional magnetic resonance imaging (fMRI) specifically implicates striatal D2-type dopamine receptors (i.e., D2 and D3) and corticostriatal connectivity in cognitive control. Low levels of striatal and midbrain D2-type receptor availability correlate with self-reported impulsivity, whereas striatal D2-type receptor availability shows positive correlation with motor response inhibition and cognitive flexibility. Impulsive choice on reward-based decision-making tasks also is related to deficits in striatal D2-type dopamine receptor availability, and there is evidence for an inverted U-shaped function in this relationship, reflecting an optimum of striatal dopaminergic activity. Findings from studies of clinical populations that present striatal dopamine D2-type receptor deficits as well as healthy control research participants identify D2-type receptors as therapeutic targets to improve cognitive control.

Portable, cost-effective PET cameras can radically expand the applicability of PET. We present here a within-participant comparison of fully quantified [ 18 F]FDG dynamic scans in healthy volunteers using the standard Biograph mCT scanner and portable CerePET scanner. Methods: Each of 20 healthy volunteers underwent dynamic [ 18 F]FDG imaging with both scanners (1-154 d apart) and concurrent arterial blood sampling. Tracer SUV, net influx rate (K i ), and the corresponding cerebral metabolic rate of glucose (CMR glu ) were quantified at regional and voxel levels. Results: At the regional level, CerePET outcome measure estimates within participants robustly correlated with Biograph mCT estimates in the neocortex, wherein the average Pearson correlation coefficients across participants ± SD were 0.83 ± 0.07 (SUV) and 0.85 ± 0.08 (K i and CMR glu ). There was also strong agreement between CerePET and Biograph mCT estimates, wherein the average regression slopes across participants were 0.84 ± 0.17 (SUV), 0.83 ± 0.17 (K i ), and 0.85 ± 0.18 (CMR glu ). There was similar bias across participants but higher correlation and less variability in subcortical regions than in cortical regions. Pearson correlation coefficients for subcortical regions equaled 0.97 ± 0.02 (SUV) and 0.97 ± 0.03 (K i and CMR glu ), and average regression slopes equaled 0.79 ± 0.14 (SUV), 0.83 ± 0.11 (K i ), and 0.86 ± 0.11 (CMR glu ). In voxelwise assessment, CerePET and Biograph mCT estimates across outcome measures were significantly different only in a cluster of left frontal white matter. Conclusion: Our results indicate robust correlation and agreement between semi- and fully quantitative brain glucose metabolism measurements from portable CerePET and standard Biograph mCT scanners. The results obtained with a portable PET scanner in this comparison in humans require follow-up but lend confidence to the feasibility of more flexible and portable brain imaging with PET., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Abstract Magnetic resonance imaging (MRI) is a powerful and versatile technique that offers a range of physiological, diagnostic, structural, and functional measurements. One of the most widely used basic contrasts in MRI diagnostics is transverse relaxation time (T2)-weighted imaging, but it provides only qualitative information. Realizing quantitative high-resolution T2 mapping is imperative for the development of personalized medicine, as it can enable the characterization of diseases progression. While ultra-high-field (≥ 7 T) MRI offers the means to gain new insights by increasing the spatial resolution, implementing fast quantitative T2 mapping cannot be achieved without overcoming the increased power deposition and radio frequency (RF) field inhomogeneity at ultra-high-fields. A recent study has demonstrated a new phase-based T2 mapping approach based on fast steady-state acquisitions. We extend this new approach to ultra-high field MRI, achieving quantitative high-resolution 3D T2 mapping at 7 T while addressing RF field inhomogeneity and utilizing low flip angle pulses; overcoming two main ultra-high field challenges. The method is based on controlling the coherent transverse magnetization in a steady-state gradient echo acquisition; achieved by utilizing low flip angles, a specific phase increment for the RF pulses, and short repetition times. This approach simultaneously extracts both T2 and RF field maps from the phase of the signal. Prior to in vivo experiments, the method was assessed using a 3D head-shaped phantom that was designed to model the RF field distribution in the brain. Our approach delivers fast 3D whole brain images with submillimeter resolution without requiring special hardware, such as multi-channel transmit coil, thus promoting high usability of the ultra-high field MRI in clinical practice.

Despite the numerous clearing techniques that emerged in the last decade, processing postmortem human brains remains a challenging task due to its dimensions and complexity, which make imaging with micrometer resolution particularly difficult. This paper presents a protocol to perform the reconstruction of volumetric portions of the human brain by simultaneously processing tens of sections with the SHORT (SWITCH - H2O2 - Antigen Retrieval - 2,2'-thiodiethanol [TDE]) tissue transformation protocol, which enables clearing, labeling, and sequential imaging of the samples with light-sheet fluorescence microscopy (LSFM). SHORT provides rapid tissue clearing and homogeneous multi-labeling of thick slices with several neuronal markers, enabling the identification of different neuronal subpopulations in both white and grey matter. After clearing, the slices are imaged via LSFM with micrometer resolution and in multiple channels simultaneously for a rapid 3D reconstruction. By combining SHORT with LSFM analysis within a routinely high-throughput protocol, it is possible to obtain the 3D cytoarchitecture reconstruction of large volumetric areas at high resolution in a short time, thus enabling comprehensive structural characterization of the human brain.

Despite decades of pursuit, human brain imaging has yet to uncover clear neural correlates of male-female behavioral differences. Given that such behavior does not always align with sex categories, we argue that neuroimaging research may find more success by partitioning subjects along nonbinary gender attributes in addition to sex. We review the handful of studies that have done this, several of which find as good or better association between brain measures and “gender” as they do with “sex.” Recent advances in operationalizing “gender” as a multidimensional variable should facilitate such studies, along with discovery-based approaches that mine brain imaging data for gender-associated attributes, independent of sex.

The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation-free reconstruction. Here, the authors describe an integrated serial sectioning polarization-sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label-free multi-contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high-throughput reconstruction of 4 × 4 × 2cm 3 sample blocks and simple registration between PSOCT and 2PM images that enable comprehensive analysis of myelin content, vascular structure, and cellular information. The high-resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin-filled cell bodies in the cortex and white matter. It is  shown that the imaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Nicotinic acetylcholinergic receptors (nAChR's) have been implicated in several brain disorders, including addiction, Parkinson's disease, Alzheimer's disease and schizophrenia. Here we report in vitro selectivity and functional properties, toxicity in rats, in vivo evaluation in humans, and comparison across species of [18 F]Nifene, a fast acting PET imaging agent for α4β2* nAChRs. Nifene had subnanomolar affinities for hα2β2 (0.34 nM), hα3β2 (0.80 nM) and hα4β2 (0.83 nM) nAChR but weaker (27-219 nM) for hβ4 nAChR subtypes and 169 nM for hα7 nAChR. In functional assays, Nifene (100 μM) exhibited 14% agonist and >50% antagonist characteristics. In 14-day acute toxicity in rats, the maximum tolerated dose (MTD) and the no observed adverse effect level (NOAEL) were estimated to exceed 40 μg/kg/day (278 μg/m2 /day). In human PET studies, [18 F]Nifene (185 MBq; 15% than males. No significant aging effect was observed in [18 F]Nifene binding over 5 decades. In all species (mice, rats, monkeys, and humans) thalamus showed highest [18 F]Nifene binding with reference region ratios >2 compared to extrathalamic regions. Our findings suggest that [18 F]Nifene PET may be used to study α4β2* nAChRs in various CNS disorders and for translational research.

PurposeTo predict signal-to-noise ratio (SNR) trends and absorbed energy in magnetic resonance imaging (MRI) of the brain up to 14T.Materials and methodsA human head in an eight-channel transmit/receive coil was simulated with Maxwell and Bloch equations to determine excitation homogeneity with radiofrequency (RF) shimming, image homogeneity, SNR, and absorbed energy in MRI from 1.5 to 14T considering realistic field distributions and relaxation properties.ResultsRF shimming alone achieved a standard deviation in excitation flip angle less than 10° in mid-brain up to 14T, but produced a small region with low excitation on a lower slice. Current reconstruction methods may produce shading artifacts at 14T. SNR increases with a greater-than-linear rate for gradient recalled echo (GRE) sequences having short (2 msec) echo time (TE) and long relaxation time (TR) (∼2.3-fold increase from 7T to 14T), but a less-than-linear rate if TE is 10 msec (∼1.6-fold increase from 7T to 14T). Depending on the sequence, SNR per square root of imaging time may produce a less-than-linear increase with B0 . Whole-head absorbed energy shows a less-than-quadratic increase with B0 (1.7-fold increase from 7T to 14T).ConclusionNumerical simulations indicate that with proper preparation and precautions, imaging of the human brain at up to 14T could be performed safely, with advantages in SNR.

Acute pain serves as a protective mechanism that alerts us to potential tissue damage and drives a behavioural response that removes us from danger. The neural circuitry critical for mounting this behavioural response is situated within the brainstem and is also crucial for producing analgesic and hyperalgesic responses. In particular, the periaqueductal grey, rostral ventromedial medulla, locus coeruleus and subnucleus reticularis dorsalis are important structures that directly or indirectly modulate nociceptive transmission at the primary nociceptive synapse. Substantial evidence from experimental animal studies suggests that plasticity within this system contributes to the initiation and/or maintenance of chronic neuropathic pain, and may even predispose individuals to developing chronic pain. Indeed, overwhelming evidence indicates that plasticity within this circuitry favours pro-nociception at the primary synapse in neuropathic pain conditions, a process that ultimately contributes to a hyperalgesic state. Although experimental animal investigations have been crucial in our understanding of the anatomy and function of the brainstem pain-modulation circuitry, it is vital to understand this system in acute and chronic pain states in humans so that more effective treatments can be developed. Recent functional MRI studies have identified a key role of this system during various analgesic and hyperalgesic responses including placebo analgesia, offset analgesia, attentional analgesia, conditioned pain modulation, central sensitisation and temporal summation. Moreover, recent MRI investigations have begun to explore brainstem pain-modulation circuitry plasticity in chronic neuropathic pain conditions and have identified altered grey matter volumes and functioning throughout the circuitry. Considering the findings from animal investigations, it is likely that these changes reflect a shift towards pro-nociception that ultimately contributes to the maintenance of neuropathic pain. The purpose of this review is to provide an overview of the human brain imaging investigations that have improved our understanding of the pain-modulation system in acute pain states and in neuropathic conditions. Our interpretation of the findings from these studies is often guided by the existing body of experimental animal literature, in addition to evidence from psychophysical investigations. Overall, understanding the plasticity of this system in human neuropathic pain conditions alongside the existing experimental animal literature will ultimately improve treatment options.

Purpose: Parallel transmit technology for MRI at 7 tesla will significantly benefit from high performance transmit arrays that offer high transmit efficiency and low mutual coupling between the individual array elements. A novel dual-mode transmit array with nested array elements has been developed to support imaging the human brain in both the single-channel (sTx) and parallel-transmit (pTx) excitation modes of a 7 tesla MRI scanner. In this work, the design, implementation, validation, specific absorption rate (SAR) management, and performance of the head coil is presented.Methods: The transmit array consisted of a nested arrangement to improve decoupling between the second-neighboring elements. Two large cut-outs were introduced in the RF shield for an open-face design to reduce claustrophobia and to allow patient monitoring. A hardware interface allows the coil to be used in both the sTx and pTx modes. SAR monitoring is done with virtual observation points (VOP) derived from human body models. The transmit efficiency and coverage is compared with the commercial single-channel and parallel-transmit head coils.Results: Decoupling inductors between the second-neighboring coil elements reduced the coupling to less than −20 dB. Local SAR estimates from the electromagnetic (EM) simulations were always less than the EM-based VOPs, which in turn were always less than scanner predictions and measurements for static and dynamic pTx waveforms. In sTx mode, we demonstrate improved coverage of the brain compared to the commercial sTx coil. The transmit efficiency is within 10% of the commercial pTx coil despite the two large cut-outs in the RF shield. In pTx mode, improved signal homogeneity was shown when the Universal Pulse was used for acquisition in vivo.Conclusion: A novel head coil which includes a nested eight-channel transmit array has been presented. The large cut-outs improve patient monitoring and reduce claustrophobia. For pTx mode, the EM simulation and VOP-based SAR management provided greater flexibility to apply pTx methods without the limitations of SAR constraints. For scanning in vivo, the coil was shown to provide an improved coverage in sTx mode compared to a standard commercial head coil.

Super-resolution three-dimensional (3-D) electromagnetic (EM) inversion for microwave human brain imaging is a typical high contrast EM inverse problem and requires huge computational costs. This work proposes a hybrid neural network electromagnetic inversion scheme (HNNEMIS) which contains shallow and deep neural networks to alleviate the required huge computational costs and solve this high contrast inverse problem. In the proposed scheme, semi-join back propagation neural network (SJ-BPNN) is employed to nonlinearly map the measured scattered electric field to two output channels, namely the permittivity and conductivity of scatterers, respectively. Such a semi-join strategy decreases the computational burden in training and testing processes. Then, a deep learning technique, termed U-Net, is employed to further enhance the imaging quality of the output from SJ-BPNN. To decrease the training cost and make neural networks fast convergent for human brain inversion, a novel training dataset construction strategy which contains the characteristics of human brain is also proposed. Noise-free and noisy numerical examples demonstrate that HNNEMIS has superior super-resolution inversion capabilities for human brain imaging. [ABSTRACT FROM AUTHOR]

In this letter, we evaluate antenna designs for ultra-high frequency and field (UHF) human brain magnetic resonance imaging (MRI) at 10.5 tesla (T). Although MRI at such UHF is expected to provide major signal-to-noise gains, the frequency of interest, 447 MHz, presents us with challenges regarding improved B 1 + and SAR efficiency near the central region of the phantom based on simulation and experiment. However, the performances of the MDH and dipole antenna arrays were overall similar when evaluating a human model in terms of peak B 1 + near the superior region of the brain for human brain imaging.1 + efficiency, 10 g SAR, and SAR efficiency. Finally, the concept of an MDH array showed an advantage in improved decoupling, SAR, and B 1 + near the superior region of the brain for human brain imaging.

Despite decades of pursuit, human brain imaging has yet to uncover clear neural correlates of male-female behavioral differences. Given that such behavior does not always align with sex categories, we argue that neuroimaging research may find more success by partitioning subjects along nonbinary gender attributes in addition to sex. We review the handful of studies that have done this, several of which find as good or better association between brain measures and "gender" as they do with "sex." Recent advances in operationalizing "gender" as a multidimensional variable should facilitate such studies, along with discovery-based approaches that mine brain imaging data for gender-associated attributes, independent of sex., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)