RF shimming in the cervical spinal cord at 7 T.

PURPOSE: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. METHODS: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. RESULTS: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1 + efficiency, and the vendor-based "patient" and "volume" modes showed the lowest B1 + efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior-inferior axis. CONCLUSION: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.

A correction algorithm for improved magnetic field monitoring with distal field probes.

PURPOSE: A significant source of artifacts in MRI are field fluctuations. Field monitoring is a new technology that allows measurement of field dynamics during a scan via "field probes," which can be used to improve image reconstruction. Ideally, probes are located within the volume where gradients produce nominally linear field patterns. However, in some situations probes must be located far from isocenter where rapid field variation can arise, leading to erroneous field-monitoring characterizations and images. This work aimed to develop an algorithm that improves the robustness of field dynamics in these situations. METHODS: The algorithm is split into three components. Component 1 calculates field dynamics one spatial order at a time, whereas the second implements a weighted least squares solution based on probe distance. Component 3 then calculates phase residuals and removes the residual phase for distant probes before recalculation. Two volunteers and a phantom were scanned on a 7T MRI using diffusion-weighted sequences, and field monitoring was performed. Image reconstructions were informed with field dynamics calculated conventionally, and with the correction algorithm, after which in vivo images were compared qualitatively and phantom image error was quantitatively assessed. RESULTS: The algorithm was able to correct corrupted field dynamics, resulting in image-quality improvements. Significant artifact reduction was observed when correcting higher-order fits. Stepwise fitting provided the most correction benefit, which was marginally improved when adding the other correction strategies. CONCLUSION: The proposed algorithm can mitigate effects of phase errors in field monitoring, providing improved characterization of field dynamics.

Single-shot spiral diffusion-weighted imaging at 7T using expanded encoding with compressed sensing.

PURPOSE: The expanded encoding model incorporates spatially- and time-varying field perturbations for correction during reconstruction. To date, these reconstructions have used the conjugate gradient method with early stopping used as implicit regularization. However, this approach is likely suboptimal for low-SNR cases like diffusion or high-resolution MRI. Here, we investigate the extent that ℓ 1 $$ {\ell}_1 $$ -wavelet regularization, or equivalently compressed sensing (CS), combined with expanded encoding improves trade-offs between spatial resolution, readout time and SNR for single-shot spiral DWI at 7T. The reconstructions were performed using our open-source graphics processing unit-enabled reconstruction toolbox, "MatMRI," that allows inclusion of the different components of the expanded encoding model, with or without CS. METHODS: In vivo accelerated single-shot spirals were acquired with five acceleration factors (R) (2×-6×) and three in-plane spatial resolutions (1.5, 1.3, and 1.1 mm). From the in vivo reconstructions, we estimated diffusion tensors and computed fractional anisotropy maps. Then, simulations were used to quantitatively investigate and validate the impact of CS-based regularization on image quality when compared to a known ground truth. RESULTS: In vivo reconstructions revealed improved image quality with retainment of small features when CS was used. Simulations showed that the joint use of the expanded encoding model and CS improves accuracy of image reconstructions (reduced mean-squared error) over the range of R investigated. CONCLUSION: The expanded encoding model and CS regularization are complementary tools for single-shot spiral diffusion MRI, which enables both higher spatial resolutions and higher R.

Shimming toolbox: An open-source software toolbox for B0 and B1 shimming in MRI.

PURPOSE: Introduce Shimming Toolbox ( https://shimming-toolbox.org), an open-source software package for prototyping new methods and performing static, dynamic, and real-time B0 shimming as well as B1 shimming experiments. METHODS: Shimming Toolbox features various field mapping techniques, manual and automatic masking for the brain and spinal cord, B0 and B1 shimming capabilities accessible through a user-friendly graphical user interface. Validation of Shimming Toolbox was demonstrated in three scenarios: (i) B0 dynamic shimming in the brain at 7T using custom AC/DC coils, (ii) B0 real-time shimming in the spinal cord at 3T, and (iii) B1 static shimming in the spinal cord at 7T. RESULTS: The B0 dynamic shimming of the brain at 7T took about 10 min to perform. It showed a 47% reduction in the standard deviation of the B0 field, associated with noticeable improvements in geometric distortions in EPI images. Real-time dynamic xyz-shimming in the spinal cord took about 5 min and showed a 30% reduction in the standard deviation of the signal distribution. B1 static shimming experiments in the spinal cord took about 10 min to perform and showed a 40% reduction in the coefficient of variation of the B1 field. CONCLUSION: Shimming Toolbox provides an open-source platform where researchers can collaborate, prototype and conveniently test B0 and B1 shimming experiments. Future versions will include additional field map preprocessing techniques, optimization algorithms, and compatibility across multiple MRI manufacturers.

A radiofrequency coil for infants and toddlers.

Infants and toddlers are a challenging population upon which to perform magnetic resonance imaging (MRI) of the brain, both in research and clinical settings. Because of the large range in head size during the early years of development, paediatric neuro-MRI requires a radiofrequency (RF) coil, or set of coils, that is tailored to head size to provide the highest image quality. Mitigating techniques must also be employed to reduce and correct for subject motion. This manuscript describes an RF coil with a tailored mechanical-electrical design that can adapt to the head size of 3-month-old infants to 3-year-old toddlers. The RF coil was designed with tight-fitting coil elements to improve the signal-to-noise ratio (SNR) in comparison with commercially available adult head coils, while simultaneously aiding in immobilization. The coil was designed without visual obstruction to facilitate an unimpeded view of the child's face and the potential application of camera or motion-tracking systems. Despite the lack of elements over the face, the paediatric coil produced higher SNR over most of the brain compared with adult coils, including more than twofold in the periphery. Acceleration rates of fourfold in each Cartesian direction could be achieved. High SNR allowed for short acquisition times through accelerated imaging protocols and reduced the probability of motion during a scan. Modification of the acquisition protocol, with immobilization of the head through the adjustable coil geometry, and subsequently being combined with a motion-tracking system, provides a compelling platform for scanning paediatric populations without sedation and with improved image quality.

An 8-channel Tx dipole and 20-channel Rx loop coil array for MRI of the cervical spinal cord at 7 Tesla.

The quality of cervical spinal cord images can be improved by the use of tailored radiofrequency (RF) coil solutions for ultrahigh field imaging; however, very few commercial and research 7-T RF coils currently exist for the spinal cord, and in particular, those with parallel transmission (pTx) capabilities. This work presents the design, testing, and validation of a pTx/Rx coil for the human neck and cervical/upper thoracic spinal cord. The pTx portion is composed of eight dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made up of twenty semiadaptable overlapping loops to produce high signal-to-noise ratio (SNR) across the patient population. The coil housing is designed to facilitate patient positioning and comfort, while also being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1 + uniformity, power efficiency, and/or specific absorption rate efficiency. B1 + homogeneity, SNR, and g-factor were evaluated in adult volunteers and demonstrated excellent performance from the occipital lobe down to the T4-T5 level. We compared the proposed coil with two state-of-the-art head and head/neck coils, confirming its superiority in the cervical and upper thoracic regions of the spinal cord. This coil solution therefore provides a convincing platform for producing the high image quality necessary for clinical and research scanning of the upper spinal cord.

Divergence of rodent and primate medial frontal cortex functional connectivity.

With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity "fingerprints" of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFC whole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC.

An open access resource for functional brain connectivity from fully awake marmosets.

The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To accelerate such progress, we present the Marmoset Functional Brain Connectivity Resource (marmosetbrainconnectome.org), currently consisting of over 70 h of resting-state fMRI (RS-fMRI) data acquired at 500 µm isotropic resolution from 31 fully awake marmosets in a common stereotactic space. Three-dimensional functional connectivity (FC) maps for every cortical and subcortical gray matter voxel are stored online. Users can instantaneously view, manipulate, and download any whole-brain functional connectivity (FC) topology (at the subject- or group-level) along with the raw datasets and preprocessing code. Importantly, researchers can use this resource to test hypotheses about FC directly - with no additional analyses required - yielding whole-brain correlations for any gray matter voxel on demand. We demonstrate the resource's utility for presurgical planning and comparison with tracer-based neuronal connectivity as proof of concept. Complementing existing structural connectivity resources for the marmoset brain, the Marmoset Functional Brain Connectivity Resource affords users the distinct advantage of exploring the connectivity of any voxel in the marmoset brain, not limited to injection sites nor constrained by regional atlases. With the entire raw database (RS-fMRI and structural images) and preprocessing code openly available for download and use, we expect this resource to be broadly valuable to test novel hypotheses about the functional organization of the marmoset brain.

Integration of an RF coil and commercial field camera for ultrahigh-field MRI.

PURPOSE: To develop an RF coil with an integrated commercial field camera for ultrahigh field (7T) neuroimaging. The RF coil would operate within a head-only gradient coil and be subject to the corresponding design constraints. The RF coil can thereafter be used for subject-specific correction of k-space trajectories-notably in gradient-sensitive sequences such as single-shot spiral imaging. METHODS: The transmit and receive performance was evaluated before and after the integration of field probes, whereas field probes were evaluated when in an optimal configuration external to the coil and after their integration. Diffusion-weighted EPI and single-shot spiral acquisitions were employed to evaluate the efficacy of correcting higher order field perturbations and the consequent effect on image quality. RESULTS: Field probes had a negligible effect on RF-coil performance, including the transmit efficiency, transmit uniformity, and mean SNR over the brain. Modest reductions in field-probe signal lifetimes were observed, caused primarily by nonidealities in the gradient and shim fields of the head-only gradient coil at the probe positions. The field-monitoring system could correct up to second-order field perturbations in single-shot spiral imaging. CONCLUSION: The integrated RF coil and field camera was capable of concurrent-field monitoring within a 7T head-only scanner and facilitated the subsequent correction of k-space trajectories during spiral imaging.

Radiofrequency coil for routine ultra-high-field imaging with an unobstructed visual field.

Many neuroscience applications have adopted functional MRI as a tool to investigate the healthy and diseased brain during the completion of a task. While ultra-high-field MRI has allowed for improved contrast and signal-to-noise ratios during functional MRI studies, it remains a challenge to create local radiofrequency coils that can accommodate an unobstructed visual field and be suitable for routine use, while at the same time not compromise performance. Performance (both during transmission and reception) can be improved by using close-fitting coils; however, maintaining sensitivity over the whole brain often requires the introduction of coil elements proximal to the eyes, thereby partially occluding the subject's visual field. This study presents a 7 T head coil, with eight transmit dipoles and 32 receive loops, that is designed to remove visual obstructions from the subject's line of sight, allowing for an unencumbered view of visual stimuli, the reduction of anxiety induced from small enclosures, and the potential for eye-tracking measurements. The coil provides a practical solution for routine imaging, including a split design (anterior and posterior halves) that facilitates subject positioning, including those with impaired mobility, and the placement of devices required for patient comfort and motion reduction. The transmit and receive coils displayed no degradation of performance due to adaptions to the design topology (both mechanical and electrical) required to create an unobstructed visual field. All computer-aided design files, electromagnetic simulation models, transmit field maps and local specific absorption rate matrices are provided to promote reproduction.

Altered Resting-State Functional Connectivity Between Awake and Isoflurane Anesthetized Marmosets.

The common marmoset (Callithrix jacchus) is a New World primate that is becoming increasingly popular as a preclinical model. To assess functional connectivity (FC) across the marmoset brain, resting-state functional MRI (RS-fMRI) is often performed under isoflurane anesthesia to avoid the effects of motion, physiological stress, and training requirements. In marmosets, however, it remains unclear how isoflurane anesthesia affects patterns of FC. Here, we investigated the effects of isoflurane on FC when delivered with either medical air or 100% pure oxygen, two canonical methods of inhalant isoflurane anesthesia delivery. The results demonstrated that when delivered with either medical air or 100% oxygen, isoflurane globally decreased FC across resting-state networks that were identified in awake marmosets. Generally, although isoflurane globally decreased FC in resting-state networks, the spatial structure of the networks was preserved. Outside of the context of RS networks, we indexed pair-wise functional connectivity between regions across the brain and found that isoflurane substantially altered interhemispheric and thalamic FC. Taken together, these findings indicate that RS-fMRI under isoflurane anesthesia is useful to evaluate the global structure of functional networks, but may obfuscate important nodes of some network components when compared to data acquired in fully awake marmosets.

Intrinsic Functional Boundaries of Lateral Frontal Cortex in the Common Marmoset Monkey.

The common marmoset (Callithrix jacchus) is a small New World primate species that has been recently targeted as a potentially powerful preclinical model of human prefrontal cortex dysfunction. Although the structural boundaries of frontal cortex were described in marmosets at the start of the 20th century (Brodmann, 1909) and refined more recently (Paxinos et al., 2012), the broad functional boundaries of marmoset frontal cortex have yet to be established. In this study, we sought to functionally derive boundaries of the marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting-state functional magnetic resonance imaging (RS-fMRI). We collected RS-fMRI data in seven (four females, three males) lightly anesthetized marmosets and used a data-driven hierarchical clustering approach to derive subdivisions of the LFC based on intrinsic functional connectivity. We then conducted seed-based analyses to assess the functional connectivity between these clusters and the rest of the brain. The results demonstrated seven distinct functional clusters within the LFC. The functional connectivity patterns of these clusters with the rest of the brain were also found to be distinct and organized along a rostrocaudal gradient, consonant with those found in humans and macaques. Overall, these results support the view that marmosets are a promising preclinical modeling species for studying LFC dysfunction related to neuropsychiatric or neurodegenerative human brain diseases.SIGNIFICANCE STATEMENT The common marmoset is a New World primate that has garnered recent attention as a powerful complement to canonical Old World primate (e.g., macaques) and rodent models (e.g., rats, mice) for preclinical modeling of the human brain in healthy and diseased states. A critical step in the development of marmosets for such models is to characterize functional network topologies of frontal cortex in healthy, normally functioning marmosets, that is, how these circuitries are functionally divided and how those topologies compare to human circuitry. To our knowledge, this is the first study to demonstrate functional boundaries of the lateral frontal cortex and the corresponding network topologies in marmoset monkeys.

Comparison of resting-state functional connectivity in marmosets with tracer-based cellular connectivity.

Resting-state functional MRI (RS-fMRI) is widely used to assess how strongly different brain areas are connected. However, this connection obtained by RS-fMRI, which is called functional connectivity (FC), simply refers to the correlation of blood oxygen level-dependent (BOLD) signals across time it has yet to be quantified how accurately FC reflects cellular connectivity (CC). In this study, we elucidated this relationship using RS-fMRI and quantitative tracer data in marmosets. In addition, we also elucidated the effects of distance between two brain regions on the relationship between FC and CC across seed region. To calculate FC, we used full correlation approach that is considered to reflect not only direct (monosynaptic connections) but also indirect pathways (polysynaptic connections). Our main findings are that: (1) overall FC obtained by RS-fMRI was highly correlated with tracer-based CC, but correlation coefficients varied remarkably across seed regions; (2) the strength of FC decreased with increase in the distance between two regions; (3) correlation coefficients between FC and CC after regressing out the effects of the distance between two regions still varied across seed regions, but some regions have strong correlations. These findings suggest that although FC reflects the strength of monosynaptic pathways, it is strongly affected by the distance between regions.

Looming and receding visual networks in awake marmosets investigated with fMRI.

An object that is looming toward a subject or receding away contains important information for determining if this object is dangerous, beneficial or harmless. This information (motion, direction, identity, time-to-collision, size, velocity) is analyzed by the brain in order to execute the appropriate behavioral responses depending on the context: fleeing, freezing, grasping, eating, exploring. In the current study, we performed ultra-high-field functional MRI (fMRI) at 9.4T in awake marmosets to explore the patterns of brain activation elicited by visual stimuli looming toward or receding away from the monkey. We found that looming and receding visual stimuli activated a large cortical network in frontal, parietal, temporal and occipital cortex in areas involved in the analysis of motion, shape, identity and features of the objects. Looming stimuli strongly activated a network composed of portions of the pulvinar, superior colliculus, putamen, parietal, prefrontal and temporal cortical areas. These activations suggest the existence of a network that processes visual stimuli looming toward peripersonal space to predict the consequence of these stimuli. Together with previous studies in macaque monkeys, these findings indicate that this network is preserved across Old and New World primates.

Elimination of low-inversion-efficiency induced artifacts in whole-brain MP2RAGE using multiple RF-shim configurations at 7 T.

The magnetization-prepared two-rapid-gradient-echo (MP2RAGE) sequence is used for structural T1 -weighted imaging and T1 mapping of the human brain. In this sequence, adiabatic inversion RF pulses are commonly used, which require the B1+ magnitude to be above a certain threshold. Achieving this threshold in the whole brain may not be possible at ultra-high fields because of the short RF wavelength. This results in low-inversion regions especially in the inferior brain (eg cerebellum and temporal lobes), which is reflected as regions of bright signal in MP2RAGE images. This study aims at eliminating the low-inversion-efficiency induced artifacts in MP2RAGE images at 7 T. The proposed technique takes advantage of parallel RF transmission systems by splitting the brain into two overlapping slabs and calculating the complex weights of transmit channels (ie RF shims) on these slabs for excitation and inversion independently. RF shims were calculated using fast methods implemented in the standard workflow. The excitation RF pulse was designed to obtain slabs with flat plateaus and sharp edges. These slabs were joined into a single volume during the online image reconstruction. The two-slab strategy naturally results in a signal-to-noise ratio loss; however, it allowed the use of independent shims to make the B1+ field exceed the adiabatic threshold in the inferior brain, eliminating regions of low inversion efficiency. Accordingly, the normalized root-mean-square errors in the inversion were reduced to below 2%. The two-slab strategy was found to outperform subject-specific kT -point inversion RF pulses in terms of inversion error. The proposed strategy is a simple yet effective method to eliminate low-inversion-efficiency artifacts; consequently, MP2RAGE-based, artifact-free T1 -weighted structural images were obtained in the whole brain at 7 T.

Intrinsic functional clustering of anterior cingulate cortex in the common marmoset.

The common marmoset (Callithrix jacchus) has garnered recent attention as a potentially powerful preclinical model and complement to other canonical mammalian models of human brain diseases (e.g., rodents and Old World non-human primates). With a granular frontal cortex and the advent of transgenic modifications, marmosets are well positioned to serve as neuropsychiatric models of prefrontal cortex dysfunction. A critical step in the development of marmosets for such models is to characterize functional network topologies of frontal cortex in healthy, normally functioning marmosets. Here, we sought to characterize the intrinsic functional connectivity of anterior cingulate cortex (ACC) in marmosets using resting state functional magnetic resonance imaging (RS-fMRI). Seven lightly anesthetized marmosets were imaged at ultra-high field (9.4 T) and hierarchical clustering was employed to extract functional clusters of ACC from the RS-fMRI data. The data demonstrated three functionally discrete clusters within ACC. The functional connectivity between these clusters with the rest of the brain was also found to be distinct, supporting the hypothesis that ACC subregions serve different circuits and their concomitant functions. In a separate seed-based analysis, we also sought to delineate finer-grained patterns of ACC connectivity between marmoset primary motor area 4ab and putative eye movement areas (8aD and 8aV). This analysis demonstrated distinct patterns of ACC functional connectivity between motor and eye movement regions that overlapped well with what has been shown in humans and macaques. Overall, these results demonstrate that marmosets have a network topology of ACC that resembles that of Old World primates, giving further credence to the use of marmosets for preclinical studies of intractable human brain diseases.

Integrated radiofrequency array and animal holder design for minimizing head motion during awake marmoset functional magnetic resonance imaging.

Marmosets are small New World primates that are posited to become an important preclinical animal model for studying intractable human brain diseases. A critical step in the development of marmosets as a viable model for human brain dysfunction is to characterize brain networks that are homologous with human network topologies. In this regard, the use of functional magnetic resonance imaging (fMRI) holds tremendous potential for functional brain mapping in marmosets. Although possible, implementation of hardware for fMRI in awake marmosets (free of the confounding effects of anesthesia) is not trivial due to the technical challenges associated with developing specialized imaging hardware. Here, we describe the design and implementation of a marmoset holder and head-fixation system with an integrated receive coil for awake marmoset fMRI. This design minimized head motion, with less than 100  µm of translation and 0.5 degrees of rotation over 15 consecutive resting state fMRI runs (at 15 min each) across 3 different marmosets. The fMRI data was of sufficient quality to reliably extract 8 resting state networks from each animal with only 60-90 min of resting state fMRI acquisition per animal. The restraint system proved to be an efficient and practical solution for securing an awake marmoset and positioning a receive array within minutes, limiting stress to the animal. This design is also amenable for multimodal imaging, allowing for electrode or lens placement above the skull via the open chamber design. All computer-aided-design (CAD) files and engineering drawings are provided as an open resource, with the majority of the parts designed to be 3D printed.

Task-based fMRI of a free-viewing visuo-saccadic network in the marmoset monkey.

Saccadic tasks are often used to index aberrations of cognitive function in patient populations, with several neuropsychiatric and neurologic disorders characterized by saccadic dysfunction. The common marmoset (Callithrix jacchus) has received recent attention as an additional primate model for studying the neural basis of these dysfunctions - marmosets are amenable to a host of genetic manipulation techniques and have a lissencephalic cortex, which is well suited for a variety of recording techniques (e.g., calcium imaging, laminar electrophysiology). Because the marmoset cortex is mostly lissencephalic, however, the locations of frontal saccade-related regions (e.g., frontal eye fields (FEF)) are less readily identified than in Old World macaque monkeys. Further, although high quality histology-based atlases do exist for marmosets, identifying these regions based on histology alone is not always accurate, with the cytoarchitectonic boundaries often inconsonant with functional boundaries. As such, there is a need to map the functional location of these regions directly. Task-based functional magnetic resonance imaging (fMRI) is of utility in this regard, allowing for detection of whole-brain signal changes in response to moving stimuli. Here, we conducted task-based fMRI in marmosets at ultra-high field (9.4 T) during a free-viewing visuo-saccadic task. We also conducted the same task in humans at ultra-high field (7 T) to validate that our simple task was indeed evoking the visuo-saccadic circuitry we expected (as defined by a meta-analysis of fMRI saccade studies). In the marmosets, we found that the task evoked a robust visuo-saccadic topology, with visual cortex (V1, V2, V3, V4) activation extending ventrally to MT, MST, FST and dorsally into V6, 19M, 23V. This topology also included putative cingulate eye field (area 32 and 24d), posterior parietal cortex (with strongest activation in lateral intraparietal area (LIP)), and a frontolateral peak in area 8 aV in marmosets, extending into 45, 46, 8aD, 6DR, 8c, 6 aV, 6DC. Overall, these results support the view that marmosets are a promising preclinical modelling species for studying saccadic dysfunction related to neuropsychiatric or neurodegenerative human brain diseases.

In vivo manganese tract tracing of frontal eye fields in rhesus macaques with ultra-high field MRI: Comparison with DWI tractography.

The saccadic eye movement system has emerged as a valuable model for studying neural circuitry related to flexible control of behavior. Although connections of the saccadic circuitry are well documented via histochemical tracers, these methods require fixed tissue and thus cannot provide longitudinal assessments of connectivity. To circumvent this, diffusion weighted imaging (DWI) is often used as a proxy for connectivity in vivo, allowing for the tracing of connections longitudinally and noninvasively. DWI, however, has certain limitations in its ability to estimate the paths of fiber tracts. Here, we demonstrate the use of manganese, in an animal model, as an MRI-based in vivo labeling technique for saccadic circuitry that allows for direct tract tracing without the need to sacrifice the animal. Manganese is a strong paramagnetic contrast agent used for T1-relaxation enhancement in MRI. Here, we locally injected MnCl2 into the frontal eye fields (FEF), a key saccadic node, of two male rhesus macaques and collected ultra-high field MRI data at 7 T (T1, DWI). The results demonstrate that MnCl2-traced FEF connections parallel those established by histochemical tracing (albeit at a lower spatial resolution) and suggest that DWI underestimates FEF connectivity, likely due to crossing fibers and small tract size. These results highlight the lack of DWI sensitivity for tracing subcortical FEF fibers, but also suggest MnCl2-based tracing as a powerful alternative for assessing these connections in vivo.

Concentric radiofrequency arrays to increase the statistical power of resting-state maps in monkeys.

The close homology of monkeys and humans has increased the prevalence of non-human-primate models in functional MRI studies of brain connectivity. To improve upon the attainable resolution in functional MRI studies, a commensurate increase in the sensitivity of the radiofrequency receiver coil is required to avoid a reduction in the statistical power of the analysis. Most receive coils are comprised of multiple loops distributed equidistantly over a surface to produce spatially independent sensitivity profiles. A larger number of smaller elements will in turn provide a higher signal-to-noise ratio (SNR) over the same field of view. As the loops become physically smaller, noise originating from the sample is reduced relative to noise originating from the coil. In this coil-noise-dominated regime, coil elements can have overlapping sensitivity profiles, yet still possess only mildly correlated noise. In this manuscript, we demonstrate that inductively decoupled, concentric coil arrays can improve temporal SNR when operating in the coil-noise-dominated regime-in contrast to what is expected for the more ubiquitous sample-noise-dominated array. A small, thin, 7-channel flexible coil is developed and operated in conjunction with an existing whole-head monkey coil. The mean and maximum noise correlation between the two arrays was 5% and 23%, respectively. When the flex coil was placed over the sensorimotor cortex, the temporal SNR improved by up to 2.3-fold in the peripheral cortex and up to 1.3-fold at a 2- to 3-cm depth within the brain. When the flex coil was placed over the frontal eye fields, resting-state maps showed substantially elevated sensitivity to correlations in the prefrontal cortex (54%), supplementary eye fields (39%), and anterior cingulate cortex (41%). The concentric-coil topology provided a pragmatic and robust means to significantly improve local temporal SNR and the statistical power of functional connectivity maps.