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The study of 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 of the human brain. The development of a multi-scale and volumetric human brain imaging technique that can measure intact brain structure would be a major technical advance. Here, we describe the development of integrated serial sectioning Polarization Sensitive Optical Coherence Tomography (PSOCT) and Two Photon Microscopy (2PM) to provide label-free multi-contrast imaging, including scattering, birefringence and autofluorescence of human brain tissue. We demonstrate that high-throughput reconstruction of 4×4×2cm3sample blocks and simple registration of PSOCT and 2PM images enable comprehensive analysis of myelin content, vascular structure, and cellular information. We show that 2μmin-plane resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical property maps on the same sample, revealing the sophisticated capillary networks and lipofuscin filled cell bodies across the cortical layers. Our method is applicable to the study of a variety of pathological processes, including demyelination, cell loss, and microvascular changes in neurodegenerative diseases such as Alzheimer’s disease (AD) and Chronic Traumatic Encephalopathy (CTE).

PURPOSE: To combine multi-slice chemical exchange saturation transfer (CEST) imaging with quasi-steady-state (QUASS) processing and demonstrate the feasibility of fast QUASS CEST MRI at 3 T. METHODS: Fast multi-slice EPI CEST imaging was developed with concatenated slice acquisition after single radio-frequency irradiation. The multi-slice CEST signal evolution was described by the spin-lock relaxation during saturation duration [Formula: see text] and longitudinal relaxation during the relaxation delay time [Formula: see text] and post-label delay (PLD), from which the QUASS CEST was generalized to fast multi-slice acquisition. In addition, numerical simulations, phantom, and normal human subjects scans were performed to compare the conventional apparent and QUASS CEST measurements with different [Formula: see text] , and PLD. RESULTS: The numerical simulation showed that the apparent CEST effect strongly depends on [Formula: see text] , and PLD, while the QUASS CEST algorithm minimizes such dependences. In the L-carnosine gel phantom, the proposed QUASS CEST effects (2.68±0.12% [mean ± SD]) were higher than the apparent CEST effects [Formula: see text]. In the human brain imaging, Bland-Altman analysis bias of the proposed QUASS CEST effects was much smaller than the PLD-corrected apparent CEST effects (0.03% vs. −0.54%), indicating the proposed fast multi-slice CEST imaging is robust and accurate. CONCLUSIONS: The QUASS processing enables fast multi-slice CEST imaging with minimal loss in the measurement of the CEST effect.

PurposeTo demonstrate the advantages of spatiotemporal magnetic field monitoring to correct eddy current-induced artifacts (ghosting and geometric distortions) in high gradient strength diffusion MRI (dMRI).MethodsA dynamic field camera with 16 NMR field probes was used to characterize eddy current fields induced from diffusion gradients for different gradients strengths (up to 300 mT/m), diffusion directions, and shots in a 3D multi-shot EPI sequence on a 3T Connectom scanner. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-resolution whole brain ex vivo dMRI. A 3D multi-shot image reconstruction framework was informed with the actual nonlinear phase evolution measured with the dynamic field camera, thereby accounting for high-order eddy currents fields on top of the image encoding gradients in the image formation model.ResultsEddy current fields from diffusion gradients at high gradient strength in a 3T Connectom scanner are highly nonlinear in space and time, inducing high-order spatial phase modulations between odd/even echoes and shots that are not static during the readout. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting approaches such as navigator- and structured low-rank-based methods or MUSE, followed by image-based distortion correction with eddy. Improved dMRI analysis is demonstrated with diffusion tensor imaging and high-angular resolution diffusion imaging.ConclusionStrong eddy current artifacts characteristic of high gradient strength dMRI can be well corrected with dynamic field monitoring-based image reconstruction, unlike the two-step approach consisting of ghosting correction followed by geometric distortion reduction with eddy.

Metadata are what makes databases searchable. Without them, researchers would have difficulty finding data with features they are interested in. Brain imaging genetics is at the intersection of two disciplines, each with dedicated dictionaries and ontologies facilitating data search and analysis. Here, we present the genetics Brain Imaging Data Structure extension, consisting of metadata files for human brain imaging data to which they are linked, and describe succinctly the genomic and transcriptomic data associated with them, which may be in different databases. This extension will facilitate identifying micro-scale molecular features that are linked to macro-scale imaging repositories, facilitating data aggregation across studies.

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 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.

Purposes We present the first in-human brain PET imaging data of the new α4β2 nicotinic acetylcholine receptor (nAChR)–targeting radioligand (+)-[18F]Flubatine. Aims were to develop a kinetic modeling-based approach to quantify (+)-[18F]Flubatine and compare the data of healthy controls (HCs) and patients with Alzheimer’s disease (AD); to investigate the partial volume effect (PVE) on regional (+)-[18F]Flubatine binding; and whether (+)-[18F]Flubatine binding and cognitive test data respective β-amyloid radiotracer accumulation were correlated. Methods We examined 11 HCs and 9 mild AD patients. All subjects underwent neuropsychological testing and [11C]PiB PET/MRI examination. (+)-[18F]Flubatine PET data were evaluated using full kinetic modeling and regional as well as voxel-based analyses. Results With 270-min p.i., the unchanged parent compound amounted to 97 ± 2%. Adequate fits of the time-activity curves were obtained with the 1 tissue compartment model (1TCM). (+)-[18F]Flubatine distribution volume (binding) was significantly reduced in bilateral mesial temporal cortex in AD patients compared with HCs (right 10.6 ± 1.1 vs 11.6 ± 1.4, p = 0.049; left 11.0 ± 1.1 vs 12.2 ± 1.8, p = 0.046; one-sided t tests each). PVE correction increased not only (+)-[18F]Flubatine binding of approximately 15% but also standard deviation of 0.4–70%. Cognitive test data and (+)-[18F]Flubatine binding were significantly correlated in the left anterior cingulate, right posterior cingulate, and right parietal cortex (r > 0.5, p 18F]Flubatine binding and [11C]PiB standardized uptake value ratios were negatively correlated in several regions; whereas in HCs, a positive correlation between cortical (+)-[18F]Flubatine binding and [11C]PiB accumulation in the white matter was found. No adverse event related to (+)-[18F]Flubatine occurred. Conclusion (+)-[18F]Flubatine is a safe and stable PET ligand. Full kinetic modeling can be realized by 1TCM without metabolite correction. (+)-[18F]Flubatine binding affinity was high enough to detect group differences. Of interest, correlation between white matter β-amyloid PET uptake and (+)-[18F]Flubatine binding indicated an association between white matter integrity and availability of α4β2 nAChRs. Overall, (+)-[18F]Flubatine showed favorable characteristics and has therefore the potential to serve as α4β2 nAChR–targeting PET ligand in further clinical trials.

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.

The successes of magnetic resonance imaging and modern optical imaging of human brain function have stimulated the development of complementary modalities that offer molecular specificity, fine spatiotemporal resolution, and sufficient penetration simultaneously. By virtue of its rich optical contrast, acoustic resolution, and imaging depth far beyond the optical transport mean free path (∼1 mm in biological tissues), photoacoustic computed tomography (PACT) offers a promising complementary modality. In this article, PACT for functional human brain imaging is reviewed in its hardware, reconstruction algorithms, in vivo demonstration, and potential roadmap.

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 offers a novel avenue for new gradient coils tailored for human brain imaging at ultrahigh field.

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 towards 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.

Third harmonic generation microscopy (THG) was used for high-resolution label-free human brain imaging. The THG images of human brain tissues show neuronal soma, dendrites, and lipofuscin in gray matter while myelinated axons in white matter.

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.

Modern neuroimaging techniques offer disctinct views on brain structure and function. Data acquired using these techniques can be analyzed in terms of its network structure to identify organizing principles at the systems level. Graph representations are flexible frameworks where nodes are related to brain regions and edges to structural or functional links. Most research to date has focused on analyzing these graphs reflecting structure or function. Graph signal processing (GSP) is an emerging area of research where signals at the nodes are studied atop the underlying graph structure. Here, we review GSP tools for brain imaging data and discuss their potential to integrate brain structure with function. We discuss how brain activity can be meaningfully filtered. We also derive surrogate data as a null model to test significance for graph signals. We review that individuals with less concentration on graph high frequency could switch attention faster.

Over the last two decades, developments of human brain stroke imaging have raised several questions about the place of new MRI biomarkers in the acute management of stroke and the prediction of poststroke outcome. Recent studies have demonstrated the main role of perfusion-weighted imaging in the identification of the best cerebral perfusion profile for a better response after reperfusion therapies in acute ischemic stroke. A major issue remains the early prediction of stroke outcome. While voxel-based lesion-symptom mapping emphasized the influence of stroke location, the analysis of the brain parenchyma underpinning the stroke lesion showed the relevance of prestroke cerebral status, including cortical atrophy, white matter integrity, or presence of chronic cortical cerebral microinfarcts. Moreover, besides the evaluation of the visually abnormal brain tissue, the analysis of normal-appearing brain parenchyma using diffusion tensor imaging and magnetization transfer imaging or spectroscopy offered new biomarkers to improve the prediction of the prognosis and new targets to follow in therapeutic trials. The aim of this review was to depict the main new radiological biomarkers reported in the last two decades that will provide a more thorough prediction of functional, motor, and neuropsychological outcome following the stroke. These new developments in neuroimaging might be a cornerstone in the emerging personalized medicine for stroke patients.

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, [18F]TRACK, for in vivo Trk positron emission tomography (PET) imaging. We describe herein central nervous system selectivity assessment and first-in-human study of [18F]TRACK.

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 µm 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.

The cerebral cholinergic system is involved in several cognitive processes and neuropsychiatric 2 diseases. For research purposes and later on in routine clinical settings new PET radioligands with more favorable characteristics than the established 3-pyridylether derivatives with their slow kinetics are necessary. Here we present the first in-human brain PET imaging data of the new α4β2 nicotinic acetylcholine receptor (nAChR)-targeting radioligand (+)-[18F]Flubatine. Primary aim of this study was to develop a kinetic modeling-based approach to quantify the α4β2 nAChR availability in the human brain and to compare respective data of healthy controls (HCs) with those of patients with Alzheimer’s disease (AD). Secondary aims were to investigate whether (+)-[18F]Flubatine binding was correlated to cognitive test data or β-amyloid radiotracer accumulation. Furthermore, the partial volume effect (PVE) on regional (+)-[18F]Flubatine binding was investigated. We examined 11 non-smoking HCs and 9 non-smoking patients with mild AD without anti-dementive drugs. Prior to (+)-[18F]Flubatine PET, all subjects underwent an extensive neuropsychological testing and a β-amyloid [11C]PiB PET/MRI examination. To evaluate the (+)-[18F]Flubatine PET data, we used full kinetic modeling (one and two tissue compartment 16 modeling (1TCM and 2TCM)) and regional as well as voxel-based analyses. 270 min p.i., the unchanged parent compound in arterial blood amounted to 97±2%. As revealed by regional analysis, (+)-[18F]Flubatine distribution volume (binding) was significantly reduced in the bilateral mesial temporal cortex in AD patients compared to HCs (right: AD: 10.6±1.1 vs HC: 11.6±1.4, p=0.049; left: AD: 11.0±1.1 vs HCs:12.2±1.8, p=0.046). Voxel-based analysis detected further clusters of reduced (+)-[18F]Flubatine in left precuneus/posterior cingulate cortex, right superior temporal and left middle temporal cortex (k>30, p0.5, p

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A framework for efficient formulation of the inverse model in diffuse optical tomography, incorporating parallel computing is proposed. Based on 24 subjects, a tenfold speed increase and a hundredfold memory efficiency is reported, whilst maintaining reconstruction quality.

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.

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.

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.

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.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.[(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 potentials1 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.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: Recently a new MR endogenous contrast mechanism was reported. It allows specifically imaging the magnetization transfer (MT) effect arising from inhomogeneously broadened components of the NMR spectrum, and was hence dubbed ihMT. Such unique NMR lineshape properties are presumably occurring in myelin because of its specifically ordered, multilayered sheath structure. Here, optimization of a pulsed ihMT preparation module is presented to provide guidance for future studies and improve the understanding of underlying contrast mechanisms. METHODS: This study was performed at 1.5 Tesla on healthy volunteers. A pulsed ihMT preparation was implemented in combination with a HASTE readout module. The pulse width, interpulse repetition time, total saturation duration and RF saturation power were considered for optimization of the ihMT sensitivity and contrast. RESULTS: An optimal configuration of the preparation module was derived, leading to 10% ihMT signal in internal capsule (relative to unsaturated data) and around 200% signal increase relative to gray matter, i.e., approximately 10-fold superior contrast compared with conventional MT ratios, measured under similar experimental conditions. CONCLUSION: Overall the ihMT sequence was robust, sensitive and very specific for white matter. These findings suggest great potential for assessing brain myelination and for better characterization of myelin related disorders. Magn Reson Med 73:2111-2121, 2015. © 2014 Wiley Periodicals, Inc.

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.

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?”.

This paper proposes YURAGI synthesis for brain imaging under the skull. The advantage of the proposed method over conventional methods is that, using YURAGI synthesis, it is possible to obtain the effective results without image registration. Image registration is generally needed when more than two images are to be synthesized into one image. YURAGI synthesis does not need image registration; thus, its method is simpler than other methods that need image synthesis. The effectiveness of the proposed method was confirmed by comparing its error rate and accuracy with those of other methods. YURAGI leads the simple and energy-saving system with performing autoregulation. Autoregulation is utilized in many biological systems. In this study, YURAGI was applied to an ultrasound-based diagnostic medical imaging technique. The experimental results using YURAGI were superior to those using othermethods. Thus, YURAGI is useful for visualizing the human brain.11. This paper has been reviewed and accepted as a regular paper. The paper was invited and incorporated into the Special Issue on Advances in Fuzzy Inference and its Related Techniques.

The introduction of hybrid positron emission/magnetic resonance tomography (PET/MR) in diagnostic clinical imaging was a major step in the evolution of ever-more sophisticated imaging systems combining two strategies formerly regarded as technically incompatible in a single device. The advent of PET/MR opened up many new avenues in clinical and research environments, mainly by providing multi-modality images obtained during a single examination. Ideally, simultaneous data acquisition with hybrid PET/MR should warrant exact image co-registration of all multi-modality image volumes provided by both systems. This assumes that there is negligible mutual electronic, technical and logistical interference on the respective simultaneous measurements. Recently, such hybrid dedicated head and whole-body systems were successfully applied in an increasing number of cases. When employed for brain imaging, PET/MR has the potential to provide high-resolution multi-modality datasets. However, it also demands careful consideration of the multitude of features offered, as well as the limitations. There are open issues that have to be considered, such as the handling of patient motion during extended periods of data acquisition, optimized sampling of derived images to ease the visual interpretation and quantitative evaluation of co-registered images. This paper will briefly summarize the current status of PET/MR within the framework of developments for image co-registration and discuss current limitations and future perspectives.

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.

Purpose Relaxation times, transmit homogeneity, signal-to-noise ratio (SNR) and parallel imaging g-factor were determined in the human brain at 3T, 7T, and 9.4T, using standard, tight-fitting coil arrays. Methods The same human subjects were scanned at all three field strengths, using identical sequence parameters and similar 31- or 32-channel receive coil arrays. The SNR of three-dimensional (3D) gradient echo images was determined using a multiple replica approach and corrected with measured flip angle and T2* distributions and the T1 of white matter to obtain the intrinsic SNR. The g-factor maps were derived from 3D gradient echo images with several GRAPPA accelerations. Results As expected, T1 values increased, T2* decreased and the B1-homogeneity deteriorated with increasing field. The SNR showed a distinctly supralinear increase with field strength by a factor of 3.10 ± 0.20 from 3T to 7T, and 1.76 ± 0.13 from 7T to 9.4T over the entire cerebrum. The g-factors did not show the expected decrease, indicating a dominating role of coil design. Conclusion In standard experimental conditions, SNR increased supralinearly with field strength (SNR ∼ B01.65). To take full advantage of this gain, the deteriorating B1-homogeneity and the decreasing T2* have to be overcome. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

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, 2017. © 2017 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 in vivo 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 T2 fitting of these images an M0 map ( M 0 MASE ) was obtained, in which signal intensity was expressed as the product of B 1 - and M 0 ( 1 - e - TR / T 1 ) . 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 α B 1 + . Water fractions in gray and white matters obtained from the M0 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.

Magnetic susceptibility varies among brain structures and provides insights into the chemical and molecular composition of brain tissues. However, the determination of an arbitrary susceptibility distribution from the measured MR signal phase is a challenging, ill-conditioned inverse problem. Although a previous method named calculation of susceptibility through multiple orientation sampling (COSMOS) has solved this inverse problem both theoretically and experimentally using multiple angle acquisitions, it is often impractical to carry out on human subjects. Recently, the feasibility of calculating the brain susceptibility distribution from a single-angle acquisition was demonstrated using morphology enabled dipole inversion (MEDI). In this study, we further improved the original MEDI method by sparsifying the edges in the quantitative susceptibility map that do not have a corresponding edge in the magnitude image. Quantitative susceptibility maps generated by the improved MEDI were compared qualitatively and quantitatively with those generated by calculation of susceptibility through multiple orientation sampling. The results show a high degree of agreement between MEDI and calculation of susceptibility through multiple orientation sampling, and the practicality of MEDI allows many potential clinical applications. Magn Reson Med, 2011. © 2011 Wiley-Liss, 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, [

Although transcranial photoacoustic imaging has been previously investigated by several groups, there are many unknowns about the distorting effects of the skull due to the impedance mismatch between the skull and underlying layers. The current computational methods based on finite-element modeling are slow, especially in the cases where fine grids are defined for a large 3-D volume. We develop a very fast modeling/simulation framework based on deterministic ray-tracing. The framework considers a multilayer model of the medium, taking into account the frequency-dependent attenuation and dispersion effects that occur in wave reflection, refraction, and mode conversion at the skull surface. The speed of the proposed framework is evaluated. We validate the accuracy of the framework using numerical phantoms and compare its results to k-Wave simulation results. Analytical validation is also performed based on the longitudinal and shear wave transmission coefficients. We then simulated, using our method, the major skull-distorting effects including amplitude attenuation, time-domain signal broadening, and time shift, and confirmed the findings by comparing them to several ex vivo experimental results. It is expected that the proposed method speeds up modeling and quantification of skull tissue and allows the development of transcranial photoacoustic brain imaging.

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