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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 -1 s -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., (© 2023. The Author(s).)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (T 2 )-weighted imaging, but it provides only qualitative information. Realizing quantitative high-resolution T 2 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 T 2 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 T 2 mapping approach based on fast steady-state acquisitions. We extend this new approach to ultra-high field MRI, achieving quantitative high-resolution 3D T 2 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 T 2 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., (© 2022. The Author(s).)

Purpose: We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate)., Methods: Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm 2 . Comparisons were made against standard pulsed gradient spin echo (PGSE) diffusion in vivo and in an isotropic diffusion phantom., Results: Simulations show that to achieve high frequency and b-value simultaneously for OGSE, high gradient amplitude, high slew rates, and high peripheral nerve stimulation limits are required. A strong linear trend for increased diffusivity (mean: 8-19%, radial: 9-27%, parallel: 8-15%) was observed in normal white matter with OGSE (20 Hz to 100 Hz) as compared to PGSE. Linear fitting to frequency provided excellent correlation, and using a short-range disorder model provided radial long-term diffusivities of D ∞,MD = 911 ± 72 µm 2 /s, D ∞,PD = 1519 ± 164 µm 2 /s, and D ∞,RD = 640 ± 111 µm 2 /s and correlation lengths of l c ,MD = 0.802 ± 0.156 µm, l c ,PD = 0.837 ± 0.172 µm, and l c ,RD = 0.780 ± 0.174 µm. Diffusivity changes with OGSE frequency were negligible in the phantom, as expected., Conclusion: The high gradient amplitude, high slew rate, and high peripheral nerve stimulation thresholds of the MAGNUS head-gradient enables OGSE acquisition for in vivo human brain imaging., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: Linking human genetics and brain imaging data is extremely challenging, among other reasons because both fields suffer from multiple comparison problems., New Method: ProcessGeneLists (PGL) links genetics and human brain imaging by using genes associated with a disease and calculating a normalized mRNA expression average of those genes in each brain region. Brain regions in which those genes are most co-expressed become regions of interest (ROIs) to perform brain imaging in participants with and without the disease, decreasing multiple comparisons. Once a region is identified as "imaging-relevant", the genes most responsible for that ROI being highlighted can be genotyped in the imaged sample. This allows to re-analyze imaging data under the light of likely relevant genetics, to study possible brain imaging/gene variant interactions., Results: As proof-of-concept, we created two lists of genes expressed in the habenula and the striatum, to verified that PGL would highlight those regions. Next, we used a list of genes likely important in alcohol abuse from the literature, which identified several brain regions previously associated with alcohol abuse such as the striatum, habenula, and hippocampus., Comparison With Existing Methods: To our knowledge there is no current method to obtain brain regions of interest from genetics data., Conclusions: Genetics typically asks "which genes are associated with a disease?" while human brain imaging typically asks "which brain regions are associated with a disease?" PGL asks "which genes, via modulation within specific brain regions, are found to be associated with a disease?"., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Optimal gradient performance is arguably a pre-requisite to realize the full potential of ultrahigh field magnetic resonance imaging (MRI). The values of using tailored gradient coils for brain imaging have been well acknowledged. Unfortunately, conventional head-only gradient coils have two major technical limitations, i.e. limited shoulder clearance and limited cooling capacity. A design, coined "flared-end" gradient coil, combined with a cooling method, named "outer-wall direct cooling", is proposed to address these problems. The "flared-end" design permits brain access to the center of gradient coil. The "flared end" structure is 3D-printed. It has electrical winding patterns (grooves) on one side and evenly spaced cooling channels on the opposite side. Electrical conductor (copper wire) is fixed into the grooves; coolant is in direct contact with the outer surface of the electrical conductor above each cooling channel, eliminating interfacial thermal resistance between coolant and copper wires. Heat transfer area is thus determined by the size and the number of cooling channels. This approach allows high electric current density for high gradient field strength while maintaining high cooling efficiency. Additionally, the symmetric coil geometry guarantees intrinsic torque balance. As a proof of concept, we have made a gradient coil prototype without active shielding. This coil has an inner diameter of 0.3 m, and is capable of generating 0.337, 0.225 and 0.485 mT/m/A along X, Y and Z, respectively. Active shielding was designed theoretically, but not pursued in the construction of this coil prototype. The new coil geometry and cooling method offer a novel avenue for new gradient coils tailored for human brain imaging at ultrahigh field., (Published by Elsevier Inc.)

The tropomyosin receptor kinase TrkA/B/C family is responsible for human neuronal growth, survival, and differentiation from early nervous system development stages onward. Downregulation of TrkA/B/C receptors characterizes numerous neurological disorders including Alzheimer's disease (AD). Abnormally expressed Trk receptors or chimeric Trk fusion proteins are also well-characterized oncogenic drivers in a variety of neurogenic and non-neurogenic human neoplasms and are currently the focus of intensive clinical research. Previously, we have described the clinical translation of a highly selective and potent carbon-11-labeled pan-Trk radioligand and the preclinical characterization of the optimized fluorine-18-labeled analogue, [ 18 F]TRACK, for in vivo Trk positron emission tomography (PET) imaging. We describe herein central nervous system selectivity assessment and first-in-human study of [ 18 F]TRACK.

A robust fully automated algorithm for identifying an arbitrary number of landmark points in the human brain is described and validated. The proposed method combines statistical shape models with trained brain morphometric measures to estimate midbrain landmark positions reliably and accurately. Gross morphometric constraints provided by automatically identified eye centers and the center of the head mass are shown to provide robust initialization in the presence of large rotations in the initial head orientation. Detection of primary midbrain landmarks are used as the foundation from which extended detection of an arbitrary set of secondary landmarks in different brain regions by applying a linear model estimation and principle component analysis. This estimation model sequentially uses the knowledge of each additional detected landmark as an improved foundation for improved prediction of the next landmark location. The accuracy and robustness of the presented method was evaluated by comparing the automatically generated results to two manual raters on 30 identified landmark points extracted from each of 30 T1-weighted magnetic resonance images. For the landmarks with unambiguous anatomical definitions, the average discrepancy between the algorithm results and each human observer differed by less than 1 mm from the average inter-observer variability when the algorithm was evaluated on imaging data collected from the same site as the model building data. Similar results were obtained when the same model was applied to a set of heterogeneous image volumes from seven different collection sites representing 3 scanner manufacturers. This method is reliable for general application in large-scale multi-site studies that consist of a variety of imaging data with different orientations, spacings, origins, and field strengths., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To improve the decoupling of a transceiver human head phased array at ultra-high fields (UHF, ≥ 7T) and to optimize its transmit (Tx) and receive (Rx) performance, a single-row eight-element (1 × 8) tight-fit transceiver overlapped loop array was developed and constructed. Overlapping the loops increases the RF field penetration depth but can compromise decoupling by generating substantial mutual resistance., Methods: Based on analytical modeling, we optimized the loop geometry and relative positioning to simultaneously minimize the resistive and inductive coupling and constructed a 9.4T eight-loop transceiver head phased array decoupled entirely by overlapping loops., Results: We demonstrated that both the magnetic and electric coupling between adjacent loops is compensated at the same time by overlapping and nearly perfect decoupling (below -30 dB) can be obtained without additional decoupling strategies. Tx-efficiency and SNR of the overlapped array outperformed that of a common UHF gapped array of similar dimensions. Parallel Rx-performance was also not compromised due to overlapping the loops., Conclusion: As a proof of concept we developed and constructed a 9.4T (400 MHz) overlapped transceiver head array based on results of the analytical modeling. We demonstrated that at UHF overlapping loops not only provides excellent decoupling but also improves both Tx- and Rx-performance. Magn Reson Med 79:1200-1211, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

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/m 2 /day). In human PET studies, [ 18 F]Nifene (185 MBq; <0.10 μg) was well tolerated with no adverse effects. Distribution volume ratios (DVR) of [ 18 F]Nifene in white matter thalamic radiations were ∼1.6 (anterior) and ∼1.5 (superior longitudinal fasciculus). Habenula known to contain α3β2 nAChR exhibited low levels of [ 18 F]Nifene binding while the red nucleus with α2β2 nAChR had DVR ∼1.6-1.7. Females had higher [ 18 F]Nifene binding in all brain regions, with thalamus showing >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., (© 2017 Wiley Periodicals, Inc.)

Encoding higher spatial resolution in simultaneous multi-slice (SMS) EPI is highly dependent on gradient performance, high density receiver coil arrays and pulse sequence optimization. We simulate gradient amplitude and slew rate determination of EPI imaging performance in terms of minimum TE, echo spacing (ES) and spatial resolution. We discuss the effects of image zooming in pulse sequences that have been used for sub-millimeter resolutions and the trade-offs in using partial Fourier and parallel imaging to reduce TE, PSF and ES. Using optimizations for SMS EPI pulse sequences with available gradient and receiver hardware, experimental results in ultra-high resolution (UHR) (0.45-0.5mm isotropic) SMS-EPI fMRI and mapping ocular dominance columns (ODC) in human brain at 0.5 mm isotropic resolution are demonstrated. We discuss promising future directions of UHR fMRI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points toward the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

The goal of this study is to optimize a 32-channel head coil array for accelerated 3T human brain proton MRI using either a Cartesian or a radial k-space trajectory. Coils had curved trapezoidal shapes and were arranged in a circular symmetry (CS) geometry. Coils were optimally overlapped to reduce mutual inductance. Low-noise pre-amplifiers were used to further decouple between coils. The SNR and noise amplification in accelerated imaging were compared to results from a head coil array with a soccer-ball (SB) geometry. The maximal SNR in the CS array was about 120% (1070 vs. 892) and 62% (303 vs. 488) of the SB array at the periphery and the center of the FOV on a transverse plane, respectively. In one-dimensional 4-fold acceleration, the CS array has higher averaged SNR than the SB array across the whole FOV. Compared to the SB array, the CS array has a smaller g-factor at head periphery in all accelerated acquisitions. Reconstructed images using a radial k-space trajectory show that the CS array has a smaller error than the SB array in 2- to 5-fold accelerations.

Purpose: To predict signal-to-noise ratio (SNR) trends and absorbed energy in magnetic resonance imaging (MRI) of the brain up to 14T., Materials and Methods: A 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., Results: RF 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)., Conclusion: Numerical 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., (© 2014 Wiley Periodicals, Inc.)

Background: Mobile computed tomography (CT) with a cone-beam source is increasingly used in the clinical field. Mobile cone-beam CT (CBCT) has great merits; however, its clinical utility for brain imaging has been limited due to problems including scan time and image quality., Objective: The aim of this study was to develop a dedicated mobile volumetric CBCT for obtaining brain images, and to optimize the imaging protocol using a brain phantom., Methods: The mobile volumetric CBCT system was evaluated with regards to scan time and image quality, measured as signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR), spatial resolution (10% MTF), and effective dose. Brain images were obtained using a CT phantom., Results: The CT scan took 5.14 s at 360 projection views. SNR and CNR were 5.67 and 14.5 at 120 kV/10 mA. SNR and CNR values showed slight improvement as the x-ray voltage and current increased (p < 0.001). Effective dose and 10% MTF were 0.92 mSv and 360 μ m at 120 kV/10 mA. Various intracranial structures were clearly visible in the brain phantom images., Conclusions: Using this CBCT under optimal imaging acquisition conditions, it is possible to obtain human brain images with low radiation dose, reproducible image quality, and fast scan time.

Purpose: Using the α7-nAChR radiotracer, [(18)F]ASEM, we present the first successful human positron emission tomography (PET) studies. Rodent occupancy with three clinically employed α7-nAChR drugs confirms the specificity of the radiotracer., Procedures: Five healthy male subjects were imaged for 90 min following IV [(18)F]ASEM. Two subjects were scanned for the second time (test/retest; TRV). Mouse biodistribution of [(18)F]ASEM was carried out in CD1 mice injected with using human equivalent doses of DMXB-A, EVP-6124, and varenicline to block specific binding., Results: [(18)F]ASEM readily entered the brain and peaked at 15 min post-injection with reversible kinetics and a peak %SUV of about 400 %. The regional human brain distribution of [(18)F]ASEM matched previous in vitro data and baboon PET results. The precuneus, parietal, occipital, cingulate cortexes, putamen, and thalamus showed high values of distribution volume (>20 ml/ml) and binding potentials >1 with TRV averaged 10.8 ± 5.1 %. In mouse distribution studies, there was significant dose-dependent blockade in the mouse brain with DMXB-A as well as the other two α7-nAChR drugs., Conclusions: The characteristics of [(18)F]ASEM are consistent with the ability to quantify α7-nAChR in the human brain. [(18)F]ASEM is suitable for imaging neuropsychiatric disorders and target engagement (receptor occupancy) of potential α7-nAChR drugs.

Purpose: Arranging transmit array elements in multiple rows provides an additional degree of freedom to correct B1 (+) field inhomogeneities and to achieve whole-brain excitation at ultrahigh field strengths. Receive arrays shaped to the contours of the anatomy increase the signal-to-noise ratio of the image. In this work, the advantages offered by the transmit and receive array techniques are combined for human brain imaging at 9.4 T., Methods: A 16-element dual-row transmit array and a 31-element receive array were developed. Based on an accurate numerical model of the transmit array, the deposited power was calculated for different head sizes and positions. The influence of the receive array on the transmit field was characterized. Parallel imaging performance and signal-to-noise ratio of the receive array were evaluated., Results: On average, a two fold increase in signal-to-noise ratio was observed in the whole-brain volume when compared with a 16-channel elliptic microstrip transceiver array. The benefits of combining the two arrays, B1 (+) shimming in three directions and high receive sensitivity, are demonstrated with high-resolution in vivo images., Conclusion: The dual-row transmit array provides whole-brain coverage at 9.4 T, which, in combination with the helmet-shaped receive array, is a valuable radio frequency configuration for ultra-high field magnetic resonance imaging of the human brain., (Copyright © 2013 Wiley Periodicals, Inc.)

We recently developed a novel cannabinoid subtype-1 (CB1) receptor radioligand (11)C-SD5024 for brain imaging. This study aimed to evaluate (11)C-SD5024 both in vitro and in vivo and compare it with the other CB1 receptor ligands previously used in humans, i.e., (11)C-MePPEP, (11)C-OMAR, (18)F-MK-9470, and (18)F-FMPEP-d2. In vitro experiments were performed to measure dissociation constant (Ki) in the human brain and to measure the lipophilicity of the five CB1 receptor ligands listed above. In vivo specific binding in monkeys was measured by comparing total distribution volume (VT) at baseline and after full receptor blockade. The kinetics of (11)C-SD5024 in humans were evaluated in seven healthy subjects with compartmental modeling. SD5024 showed Ki=0.47nM, which was at an intermediate level among the five CB1 receptor ligands. Lipophilicity (LogD7.4) was 3.79, which is appropriate for brain imaging. Monkey scans showed high proportion of specific binding: ~80% of VT. In humans, (11)C-SD5024 showed peak brain uptake of 1.5-3 standardized uptake value, which was slightly higher than that of (11)C-OMAR and (18)F-MK-9470. One-compartment model showed good fitting, consistent with the vast majority of brain uptake being specific binding found in the monkey. Regional VT values were consistent with known distribution of CB1 receptors. VT calculated from 80 and 120min of scan data was strongly correlated (R(2)=0.97), indicating that 80min provided adequate information for quantitation and that the influence of radiometabolites was low. Intersubject variability for VT of (11)C-SD5024 was 22%, which was low among the five radioligands and indicated precise measurement. In conclusion, (11)C-SD5024 has appropriate affinity and lipophilicity, high specific binding, moderate brain uptake, and provides good precision to measure the binding. The results suggest that (11)C-SD5024 is slightly better than or equivalent to (11)C-OMAR and that both are suitable for clinical studies, especially those that involve two scans in one day., (© 2013.)

For human brain imaging at ultrahigh fields, the traveling wave concept can provide a more uniform B1+ field over a larger field of view with improved patient comfort compared to conventional volume coils. It suffers, however, from limited transmit efficiency and receive sensitivity and is not readily applicable in systems where the radiofrequency shield is too narrow to allow for unattenuated wave propagation. Here, the near field of a capacitively adjustable patch antenna for excitation is combined with a receive-only array at 9.4 T. The antenna is designed in compact size and placed in close proximity to the subject to improve the transmit efficiency in narrow bores. Experimental and numerical comparisons to conventional microstrip arrays reveal improved B1+ homogeneity and longitudinal coverage, but at the cost of elevated local specific absorption rate. High-resolution functional and anatomical images demonstrate the use of this setup for in vivo human brain imaging at 9.4 T., (Copyright © 2012 Wiley Periodicals, Inc.)

The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT(1A), 5-HT(1B), 5-HT(2A), and 5-HT(4) receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging., (© 2011 Wiley Periodicals, Inc.)

Purpose: The aim of this work is to evaluate a new eight-channel transceiver (TxRx) coaxial dipole array for imaging of the human head at 9.4T developed to improve specific absorption rate (SAR) performance, and provide for a more compact and robust alternative to the state-of-the art dipole arrays., Methods: First, the geometry of a single coaxial element was optimized to minimize peak SAR and sensitivity to the load variation. Next, a multi-tissue voxel model was used to numerically simulate a TxRx array coil that consisted of eight coaxial dipoles with the optimal configuration. Finally, we compared the developed array to other human head dipole arrays. Results of numerical simulations were verified on a bench and in the scanner including in vivo measurements on a healthy volunteer., Results: The developed eight-element coaxial dipole TxRx array coil showed up to 1.1times higher SAR-efficiency than a similar in geometry folded-end and fractionated dipole array while maintaining whole brain coverage and low sensitivity of the resonance frequency to variation in the head size., Conclusion: As a proof of concept, we developed and constructed a prototype of a 9.4T (400 MHz) human head array consisting of eight TxRx coaxial dipoles. The developed array improved SAR-efficiency and provided for a more compact and robust alternative to the folded-end dipole design. To the best of our knowledge, this is the first example of using coaxial dipoles for human head MRI at ultra-high field., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

A new method of non-uniform image correction is proposed. Image non-uniformity is originated from the spatial distribution of RF transmission and reception fields, represented as B(1)(+) and B(1)(-), respectively. In our method, B(1)(+) mapping was performed invivo by a phase method. In B(1)(-) mapping, images with multiple TEs were acquired with a multi-echo adiabatic spin echo (MASE) sequence which enables homogeneous excitation. By T(2) fitting of these images an M(0) map (M(0)(MASE)) was obtained, in which signal intensity was expressed as the product of B(1)(-) and M₀(1-e⁻(TR/T¹)) . The ratio of this M(0)(MASE) map to the B(1)(+) map showed a similar spatial pattern in different human brains. These ratios of M(0)(MASE) to B(1)(+) in 24 subjects were averaged and then fitted with a spatially polynomial function to obtain a ratio map of B(1)(-)/B(1)(+)(α). Uniform image was achieved in spin echo (SE), MASE and inversion recovery turboFLASH (IRTF) images using measured B(1)(+) and calculated B(1)(-) by αB(1)(+). Water fractions in gray and white matters obtained from the M(0) images corrected by this method were in good agreement with previously reported values. From these experimental results, the proposed method of non-uniformity correction is validated at 4.7 T imaging., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: P-glycoprotein (P-gp) is a membrane-bound efflux pump that limits the distribution of drugs to several organs of the body. At the blood-brain barrier, P-gp blocks the entry of both loperamide and its metabolite, N-desmethyl-loperamide (N-dLop), and thereby prevents central opiate effects. Animal studies have shown that (11)C-dLop, compared with (11)C-loperamide, is an especially promising radiotracer because it generates negligible radiometabolites that enter the brain. The purposes of this study were to determine whether (11)C-dLop is a substrate for P-gp at the blood-brain barrier in humans and to measure the distribution of radioactivity in the entire body to estimate radiation exposure., Methods: Brain PET scans were acquired in 4 healthy subjects for 90 min and included concurrent measurements of the plasma concentration of unchanged radiotracer. Time-activity data from the whole brain were quantified using a 1-tissue-compartment model to estimate the rate of entry (K(1)) of radiotracer into the brain. Whole-body PET scans were acquired in 8 healthy subjects for 120 min., Results: For brain imaging, after the injection of (11)C-dLop the concentration of radioactivity in the brain was low (standardized uptake value, approximately 15%) and stable after approximately 20 min. In contrast, uptake of radioactivity in the pituitary was about 50-fold higher than that in the brain. The plasma concentration of (11)C-dLop declined rapidly, but the percentage composition of plasma was unusually stable, with the parent radiotracer constituting 85% of total radioactivity after approximately 5 min. The rate of brain entry was low (K(1) = 0.009 +/- 0.002 mL.cm(-3).min(-1); n = 4). For whole-body imaging, as a measure of radiation exposure to the entire body the effective dose of (11)C-dLop was 7.8 +/- 0.6 muSv/MBq (n = 8)., Conclusion: The low brain uptake of radioactivity is consistent with (11)C-dLop being a substrate for P-gp in humans and confirms that this radiotracer generates negligible quantities of brain-penetrant radiometabolites. In addition, the low rate of K(1) is consistent with P-gp rapidly effluxing substrates while they transit through the lipid bilayer. The radiation exposure of (11)C-dLop is similar to that of many other (11)C-radiotracers. Thus, (11)C-dLop is a promising radiotracer to study the function of P-gp at the blood-brain barrier, at which impaired function would allow increased uptake into the brain.

Objective: To evaluate a transverse electromagnetic (TEM), a circularly polarized (CP) (birdcage), and a 12-channel phased array head coil at the clinical field strength of B0 = 3T in terms of signal-to-noise ratio (SNR), signal homogeneity, and maps of the effective flip angle alpha., Materials and Methods: SNR measurements were performed on low flip angle gradient echo images. In addition, flip angle maps were generated for alpha(nominal) = 30 degrees using the double angle method. These evaluation steps were performed on phantom and human brain data acquired with each coil. Moreover, the signal intensity variation was computed for phantom data using five different regions of interest., Results: In terms of SNR, the TEM coil performs slightly better than the CP coil, but is second to the smaller 12-channel coil for human data. As expected, both the TEM and the CP coils show superior image intensity homogeneity than the 12-channel coil, and achieve larger mean effective flip angles than the combination of body and 12-channel coil with reduced radio frequency power deposition., Conclusion: At 3T the benefits of TEM coil design over conventional lumped element(s) coil design start to emerge, though the phased array coil retains an advantage with respect to SNR performance.

This review synthesizes our current knowledge on the neurobiology of psychosis from an array of in vivo brain-imaging studies. The evidence base consists of hundreds of studies of patients with schizophrenia and fewer on bipolar disorder but rarely providing direct comparisons between the disorders or integration across methods. Replicated findings in schizophrenia include reduced whole-brain and hippocampal volume as potential vulnerability markers, with further progression at onset; reduced N-acetyl aspartate concentrations in hippocampus and prefrontal cortex; striatal dopamine D(2) receptors upregulation; and alteration in the relation between frontal and temporal activation. These findings are not attributable to medication effects but are of unclear specificity and may apply across the psychosis spectrum. There are consistently replicated associations of psychotic symptoms and cognitive impairment in both structural and functional imaging in schizophrenia but not, as yet, in bipolar disorder. Therefore, it would be premature to dispense with current diagnostic categories because direct comparisons among them are rare, insufficient studies have examined longitudinal changes, and long-term imaging outcome studies in first-episode psychosis have not yet been done. To address these issues and make neuroimaging "clinically relevant," investigators will need to standardize their approaches to data acquisition and analysis, and construct the necessary range of "human brain maps," to implement studies that are sufficiently powered to provide reliable data pertinent to deconstructing psychosis.

Fear extinction is the decrease in conditioned fear responses that normally occurs when a conditioned stimulus (CS) is repeatedly presented in the absence of the aversive unconditioned stimulus (US). Extinction does not erase the initial CS-US association, but is thought to form a new memory. After extinction training, extinction memory competes with conditioning memory for control of fear expression. Deficits in fear extinction are thought to contribute to post-traumatic stress disorder (PTSD). Herein, we review studies performed in rats showing that the medial prefrontal cortex plays a critical role in the retention and expression of extinction memory. We also review human studies indicating that prefrontal areas homologous to those critical for extinction in rats are structurally and functionally deficient in patients with PTSD. We then discuss how findings from rat studies may allow us to: (1) develop new fear extinction paradigms in humans, (2) make specific predictions as to the location of extinction-related areas in humans, and (3) improve current extinction-based behavioral therapies for anxiety disorders.

Over the past decade, functional neuroimaging has contributed greatly to our knowledge about the neuropharmacology of substance misuse in man. Techniques such as functional magnetic resonance imaging, positron emission tomography (PET) or single photon emission tomography (SPET) can measure changes in regional cerebral activity, whereas changes in neuropharmacological parameters (e.g. receptor number and neurotransmitter levels) can be directly measured only with PET and SPET. Recently, a series of studies have shown common effects of substances of misuse on the brain, such as an acute increase in dopamine release (followed by hypofunction after chronic use) and cue exposure-induced activation of the frontal cortex, as well as specific effects, such as ecstasy-induced decreases in serotonergic transporters and occupancy of opiate receptors by substitute drugs (e.g. methadone and buprenorphine) in opiate addicts.

There are numerous methods designed to monitor brain neuropathologies resulting from a wide arsenal of insults. Regardless of the cause of neuronal death, reactive glial cells always appear at and around the site of degeneration. These cells are distinguished by the exceptional abundance of peripheral benzodiazepine receptors, particularly compared with surrounding neurons. Measuring the binding of specific ligands to these peripheral benzodiazepine receptors offers a unique indirect marker for reliable damage assessment in the CNS and a faithful indicator for the accompanying cognitive deficits.

Sharing scientific data containing complex information requires new concepts and new technology. NEUROGENERATOR is a database generator for the neuroimaging community. A database generator is a database that generates new databases. The scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes the data in a uniform way to create databases of homogeneous data suitable for data sharing, met-analysis and modelling the human brain at the systems level. These databases are then distributed to the scientists.

Human neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging have made possible the study of large-scale distributed networks in the behaving human brain. Although many imaging studies support and extend knowledge gained from other experimental modalities such as animal single-cell recordings, there have also been a substantial number of experiments that appear to contradict the animal studies. Part of the reason for this is that neuroimaging is an indirect measure of neuronal firing activity, and thus interpretation is difficult. Computational modeling can help to bridge the gap by providing a substrate for making explicit the assumptions and constraints provided from other sources such as anatomy, physiology and behavior. We describe a large-scale model of working memory that we have used to examine a number of issues relating to the interpretation of imaging data. The gating mechanism that regulates engagement and retention of short-term memory is revised to better reflect hypothesized underlying neuromodulatory mechanisms. It is shown that in addition to imparting better performance for the memory circuit, this mechanism also provides a better match to imaging data from working memory studies.

The selective nature of human perception and action implies a modulatory interaction between sensorimotor processes and attentional processes. This paper explores the use of functional imaging in humans to explore the mechanisms of perceptual selection and the fate of irrelevant stimuli that are not selected. Experiments with positron emission tomography show that two qualitatively different patterns of modulation of cerebral blood flow can be observed in experiments where non-spatial visual attention and auditory attention are manipulated. These patterns of modulation of cerebral blood flow modulation can be described as gain control and bias signal mechanisms. In visual and auditory cortex, the dominant change in cerebral blood flow associated with attention to either modality is related to a bias signal. The relation of these patterns of modulation to attentional effects that have been observed in single neurons is discussed. The existence of mechanisms for selective perception raises the more general question of whether irrelevant ignored stimuli are nevertheless perceived. Lavie's theory of attention proposes that the degree to which ignored stimuli are processed varies depending on the perceptual load of the current task. Evidence from behavioural and functional magnetic resonance imaging studies of ignored visual motion processing is presented in support of this proposal.

We propose a model that draws together experimental evidence from anatomical, electrophysiological and imaging experiments in order to understand better the neural substrate of human imaging studies using positron electron tomography (PET) and functional magnetic resonance imaging (fMRI). First, we define a simple local circuit that reflects the major role that local connectivity plays in producing PET and fMRI data, which are thought to mainly reflect synaptic activity. Second, in order to account for the role of varying behaviors during the course of a typical imaging experiment, we propose a local circuit that can perform a delayed match-to-sample task. The elements of this circuit behave very much like neurons that have been found in the prefrontal cortex during similar tasks in monkeys. One subpopulation responds selectively only when stimuli are present. Two different populations show the two types of delay-period activity that have been identified, one with high activity both during the cue and the delay period, the other with a rise during the delay period only. Last, a subpopulation shows a brief response only if the second stimulus matches the first, thus mediating the decision about whether the stimuli match. We show that in addition to performing the task, the integrated summed synaptic activities of the model are similar to experimental PET data.

Decades of psychosis research highlight the prevalence and the clinical significance of negative emotions, such as fear and anxiety. Translational evidence demonstrates the pivotal role of the amygdala in fear and anxiety. However, most of these approaches have used hypothesis-driven analyses with predefined regions of interest. A data-driven analysis may provide a complimentary, unbiased approach to identifying brain correlates of fear and anxiety. The aim of the current study was to identify the brain basis of fear and anxiety in early psychosis and controls using a data-driven approach. We analyzed data from the Human Connectome Project for Early Psychosis, a multi-site study of 125 people with psychosis and 58 controls with resting-state fMRI and clinical characterization. Multivariate pattern analysis of whole-connectome data was used to identify shared and psychosis-specific brain correlates of fear and anxiety using the NIH Toolbox Fear-Affect and Fear-Somatic Arousal scales. We then examined clinical correlations of Fear-Affect scores and connectivity patterns. Individuals with psychosis had higher levels of Fear-Affect scores than controls (p < 0.05). The data-driven analysis identified a cluster encompassing the amygdala and hippocampus where connectivity was correlated with Fear-Affect score (p < 0.005) in the entire sample. The strongest correlate of Fear-Affect was between this cluster and the anterior insula and stronger connectivity was associated with higher Fear-Affect scores (r = 0.31, p = 0.0003). The multivariate pattern analysis also identified a psychosis-specific correlate of Fear-Affect score between the amygdala/hippocampus cluster and a cluster in the ventromedial prefrontal cortex (VMPFC). Higher Fear-Affect scores were correlated with stronger amygdala/hippocampal-VMPFC connectivity in the early psychosis group (r = 0.33, p = 0.002), but not in controls (r = -0.15, p = 0.28). The current study provides evidence for the transdiagnostic role of the amygdala, hippocampus, and anterior insula in the neural basis of fear and anxiety and suggests a psychosis-specific relationship between fear and anxiety symptoms and amygdala/hippocampal-VMPFC connectivity. Our novel data-driven approach identifies novel, psychosis-specific treatment targets for fear and anxiety symptoms and provides complimentary evidence to decades of hypothesis-driven approaches examining the brain basis of threat processing., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Compared with lower field strengths, DWI at 7 T faces the combined challenges of increased distortion and blurring due to B 0 inhomogeneity, and increased signal dropouts due to B 1 + limitations using slice-specific static parallel transmission (pTx) in a multi-shot, readout-segmented EPI diffusion imaging sequence.1 + limitations using slice-specific static parallel transmission (pTx) in a multi-shot, readout-segmented EPI diffusion imaging sequence., Methods: DWI was performed in 7 healthy subjects using MRI at 7 T and readout-segmented EPI. Data were acquired with non-pTx circular-polarized (CP) pulses (CP-DWI) and static pTx pulses (pTx-DWI) using slice-specific B 1 + shim coefficients. Each volunteer underwent two scan sessions on the same day, with two runs of each sequence in the first session and one run in the second. The sequences were evaluated by assessing image quality, flip-angle homogeneity, and intrasession and intersession repeatability in ADC estimates., Results: pTx-DWI significantly reduced signal voids compared with CP-DWI, particularly in inferior brain regions. The use of pTx also improved RF uniformity and symmetry across the brain. These effects translated into improved intrasession and intersession repeatability for pTx-DWI. Additionally, re-optimizing the pTx pulse between repeat scans did not have a negative effect on ADC repeatability., Conclusion: The study demonstrates that pTx provides a reproducible image-quality increase in multishot DWI at 7 T. The benefits of pTx also extend to quantitative ADC estimation with regard to the improvement in intrasession and intersession repeatability. Overall, the combination of multishot imaging and pTx can support the development of reliable, high-resolution DWI for clinical studies at 7 T., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: To demonstrate magnetization transfer (MT) effects with low specific absorption rate (SAR) on ultra-low-field (ULF) MRI., Methods: MT imaging was implemented by using sinc-modulated RF pulse train (SPT) modules to provide bilateral off-resonance irradiation. They were incorporated into 3D gradient echo (GRE) and fast spin echo (FSE) protocols on a shielding-free 0.055T head scanner. MT effects were first verified using phantoms. Brain MT imaging was conducted in both healthy subjects and patients., Results: MT effects were clearly observed in phantoms using six SPT modules with total flip angle 3600° at central primary saturation bands of approximate offset ±786 Hz, even in the presence of large relative B 0 inhomogeneity. For brain, strong MT effects were observed in gray matter, white matter, and muscle in 3D GRE and FSE imaging using six and sixteen SPT modules with total flip angle 3600° and 9600°, respectively. Fat, cerebrospinal fluid, and blood exhibited relatively weak MT effects. MT preparation enhanced tissue contrasts in T2-weighted and FLAIR-like images, and improved brain lesion delineation. The estimated MT SAR was 0.0024 and 0.0008 W/kg for two protocols, respectively, which is far below the US Food and Drug Administration (FDA) limit of 3.0 W/kg., Conclusion: Robust MT effects can be readily obtained at ULF with extremely low SAR, despite poor relative B 0 homogeneity in ppm. This unique advantage enables flexible MT pulse design and implementation on low-cost ULF MRI platforms to achieve strong MT effects in brain and beyond, potentially augmenting their clinical utility in the future., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Currently, brain iron content represents a new neuromarker for understanding the physiopathological mechanisms leading to Parkinson's disease (PD). In vivo quantification of biological iron is possible by reconstructing magnetic susceptibility maps obtained using quantitative susceptibility mapping (QSM). Applying QSM is challenging, as up to now, no standardization of acquisition protocols and phase image processing has emerged from referenced studies. Our objectives were to compare the accuracy and the sensitivity of 10 QSM pipelines built from algorithms from the literature, applied on phantoms data and on brain data. Two phantoms, with known magnetic susceptibility ranges, were created from several solutions of gadolinium chelate. Twenty healthy volunteers from two age groups were included. Phantoms and brain data were acquired at 1.5 and 3 T, respectively. Susceptibility-weighted images were obtained using a 3D multigradient-recalled-echo sequence. For brain data, 3D anatomical T1- and T2-weighted images were also acquired to segment the deep gray nuclei of interest. Concerning in vitro data, the linear dependence of magnetic susceptibility versus gadolinium concentration and deviations from the theoretically expected values were calculated. For brain data, the accuracy and sensitivity of the QSM pipelines were evaluated in comparison with results from the literature and regarding the expected magnetic susceptibility increase with age, respectively. A nonparametric Mann-Whitney U-test was used to compare the magnetic susceptibility quantification in deep gray nuclei between the two age groups. Our methodology enabled quantifying magnetic susceptibility in human brain and the results were consistent with those from the literature. Statistically significant differences were obtained between the two age groups in all cerebral regions of interest. Our results show the importance of optimizing QSM pipelines according to the application and the targeted magnetic susceptibility range, to achieve accurate quantification. We were able to define the optimal QSM pipeline for future applications on patients with PD., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: This work aims to improve the speed of balanced SSFP (bSSFP) acquisition with segmented 3D stack-of-spirals for functional brain studies at ultrahigh field., Methods: Functional experiments were performed with an accelerated 3D stack-of-spirals sequence with water excitation for fat suppression. The resulting data were reconstructed using an iterative algorithm with corrections for system imperfections such as trajectory deviations and B 0 inhomogeneity. In the first set of experiments, we evaluated the signal change and stability with respect to echo and TR for a full-field checkerboard stimulus. To demonstrate the high spatio-temporal resolution of the developed method, the results of three optimized protocols at submillimeter resolution (0.6-mm isotropic and 0.8-mm isotropic) and at 1.2 mm isotropic resolution for whole-brain coverage were shown., Results: Water excitation and the model-based iterative reconstruction improved image quality. The BOLD-related signal changes increased with longer TE and longer TR. We observed an increase in thermal noise performance at lower TE and higher TR. However, signal stability deteriorates at higher TE and TR. Therefore, optimized protocols used shorter TE and moderately long TR to maximize the sensitivity and speed. Reproducible activations were detected along the gray-matter gyri in the submillimeter protocols with a median signal change of approximately 4% across subjects., Conclusions: Three-dimensional stack-of-spirals enables passband balanced SSFP functional imaging at a much higher spatial and temporal scale, compared with conventional spoiled gradient-echo train sequences., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Quantitative multi-parameter mapping (MPM) provides maps of physical quantities representing physiologically meaningful tissue characteristics, which allows to investigate microstructure-function relationships reflecting normal or pathologic processes in the brain. However, the achievable spatial resolution and stability of MPM for basic research or clinical applications is severely constrained by SNR limits of the MR acquisition process, resulting in relatively long acquisition times. To increase SNR, we denoise MPM acquisitions using principal component analysis along tensors exploiting the Marchenko-Pastur law (tMPPCA)., Methods: tMPPCA denoising was applied to three sets of MPM raw data before the quantification of maps of proton density, magnetization transfer saturation, R 1 , and R 2 *. The regional SNR gain for high-resolution MPM was investigated as well as reproducibility gains for clinically optimized protocols with moderate and high acceleration factors at different image resolutions., Results: Substantial noise reduction in raw data was achieved, resulting in reduced noise for quantitative mapping up to sixfold without introducing bias of mean values (below 1%). Scan-rescan fluctuations were reduced up to threefold. Denoising allowed to decrease the voxel volume fourfold at the same scan time or reduce the scan time twofold at same voxel volume without loss of sensitivity., Conclusions: tMPPCA denoising can (a) improve of fine spatial and temporal patterns, (b) considerably reduce scan time for clinical applications, or (c) increase resolution to potentially push cutting-edge MPM protocols from the upper to the lower limit of the mesoscopic scale., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT 4 ) in a cohort of healthy individuals (N = 254) and, for 5-HT 4, in a cohort of unmedicated patients with depression (N = 90). To do so, we quantified SLC6A4/TPH2 methylation using bisulfite pyrosequencing and estimated brain 5-HT 4 and 5-HTT levels using positron emission tomography. In addition, we explored the association between SLC6A4 and TPH2 methylation and measures of early life and recent stress, depressive and anxiety symptoms on 297 healthy individuals., Results: We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity., Conclusions: We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms., (© 2024. The Author(s).)

Objective: We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set., Research Fields: The 14 Tesla system can be considered a 'mesocope': a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes., Conclusions: The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR., (© 2023. The Author(s).)

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non-invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [ 15 O]H 2 O and [ 18 F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D 2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine-enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine-enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non-monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P 2 X 7 receptor, type 1 cannabinoid receptor (CB 1 ), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed., (© 2022 International Society for Neurochemistry.)

Purpose: To develop a method for unwrapping temporally undersampled and nonlinear gradient recalled echo (GRE) phase., Theory and Methods: Temporal unwrapping is performed as a sequential one step prediction of the echo phase, followed by a correction to the nearest integer wrap-count. A spatio-temporal extension of the 1D predictor corrector unwrapping (PCU) algorithm improves the prediction accuracy, and thereby maintains spatial continuity. The proposed method is evaluated using numerical phantom, physical phantom, and in vivo brain data at both 3 T and 9.4 T. The unwrapping performance is compared with the state-of-the-art temporal and spatial unwrapping algorithms, and the spatio-temporal iterative virtual-echo based Nyquist sampled (iVENyS) algorithm., Results: Simulation results showed significant reduction in unwrapping errors at higher echoes compared with the state-of-the-art algorithms. Similar to the iVENyS algorithm, the PCU algorithm was able to generate spatially smooth phase images for in vivo data acquired at 3 T and 9.4 T, bypassing the use of additional spatial unwrapping step. A key advantage over iVENyS algorithm is the superior performance of PCU algorithm at higher echoes., Conclusion: PCU algorithm serves as a robust phase unwrapping method for temporally undersampled and nonlinear GRE phase, particularly in the presence of high field gradients., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: Ultra-high field (UHF) provides improved SNR which greatly benefits SNR starved imaging techniques such as perfusion imaging. However, transmit field (B 1 + ) inhomogeneities commonly observed at UHF hinders the excitation uniformity. Here we show how replacing standard excitation pulses with parallel transmit pulses can improve efficiency of velocity selective labeling., Methods: The standard tip-down and tip-up excitation pulses found in a velocity selective preparation module were replaced with tailored non-selective k T -points pulse solutions. Bloch simulations and experimental validation on a custom-built flow phantom and in vivo was performed to evaluate different pulse configurations in circularly polarized mode (CP-mode) and parallel transmit (pTx) mode., Results: Tailored pTx pulses significantly improved velocity selective labeling fidelity and signal uniformity. The transverse magnetization normalized RMS error was reduced from 0.489 to 0.047 when compared to standard rectangular pulses played in CP-mode. Simulations showed that manipulation of time symmetry in the tailored pTx pulses is vital in minimizing residual magnetization. In addition, in vivo experiments achieved a 44% lower RF power output and a shorter pulse duration when compared to using adiabatic pulses in CP-mode., Conclusion: Using tailored pTx pulses for excitation within a velocity selective labeling preparation mitigated transmit field artifacts and improved SNR and contrast fidelity. The improvement in labeling efficiency highlights the potential of using pTx to improve robustness and accessibility of flow-based sequences such as velocity selective spin labeling at ultra-high field., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)