Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging.Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers.Therefore, contrast agents are often used to improve MRI diagnostic sensitivity.However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity.The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo.Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed.The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe -/ -) by MRI.Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s -1 mM -1 , r2 = 1555 s -1 mM -1 under a 1.5-T magnetic field; and r1 = 428 s -1 mM -1 and r2 = 1286 s -1 mM -1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s -1 mM -1 ) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field.Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch.Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.
Humans are sensitive to others' gaze direction. Evidence from a behavior study using continuous flash suppression (CFS) suggests that faces with direct and averted gaze are processed differently before they reach conscious awareness (Stein et al. 2011). An ERP study showed that invisible faces with direct gaze elicited significantly larger negative deflections at 200, 250, and 300 ms over the parietofrontal electrodes (Yokoyama et al. 2013). These results suggest that faces with direct gaze are preferentially processed in the brain unconsciously. In the current fMRI study we investigated whether brain regions involved in face and gaze processing were sensitive to gaze information rendered invisible through CFS. With a slow event-related design, four types of stimuli were presented to observers: visible and invisible faces with direct and averted gaze. The four conditions were shown in random order in each scan session, and observers were instructed to press a button to indicate when they saw a face. To minimize the physical difference between the two visibility conditions and to mimic the perception when faces leak from CFS in the invisible conditions, the same kind of noises were blended in the same eye with faces in the visible trials. Data from observers who saw any face during invisible trials were excluded from analysis. Results show that although signals from invisible faces were significantly reduced relative to visible faces, a number of brain regions, including the OFA, FFA, and the amygdala, responded differentially to invisible faces with direct vs. averted gazes. STS also responded moderately, but more variably, to invisible faces. There was a tendency for the invisible faces with the direct gaze to elicit stronger responses than invisible faces with an averted gaze; a tendency not observed for visible faces. Our results provide the neural correlates for the unconscious processing of gaze information. Meeting abstract presented at VSS 2014
Behaviors from blindsight patients as well as studies using interocular suppression suggest that the human subcortical pathway might be capable of processing object category information. Using functional MRI, we investigated subcortical response properties as well as functional connectivity patterns during object perception. During the experiment, subjects viewed objects from four different categories (tools, faces, phase-scrambled tools, phase-scrambled faces). Luminance and RMS contrast were matched for different stimuli. fMRI activity in the SC and LGN showed stronger responses to intact objects than to scrambled objects. We also performed granger causality analyses to investigate the functional connectivity of these subcortical regions with cortical regions underlying visual object processing. Preliminary results suggested a number of interesting connection patterns for different subcortical nuclei. For example, the left and right SC might have different connection patterns during object perception: although left SC showed more robust object sensitivity in terms of response amplitude, its signal was not related to responses in cortical areas; whereas right SC showed more correlation with responses in cortical areas, including both the parietal and fusiform areas. Thus we found object sensitivity in some subcortical structures, such as the SC and LGN. Preliminary results showed that subcortical nuclei might have differential patterns of communication with cortical regions during object information processing. Meeting abstract presented at VSS 2013
Abstract Quality sleep is vital for physical and mental health. No matter whether sleep problems are a consequence of or contributory factor to mental disorders, people with psychosis often suffer from severe sleep disturbances. Previous research has shown that acute sleep deprivation (SD) can cause transient brain dysfunction and lead to various cognitive impairments in healthy individuals. However, the relationship between sleep disturbance and bistable perception remains unclear. Here, we investigated whether the bistable perception could be affected by SD and elucidated the functional brain changes accompanying SD effects on bistable perception using functional magnetic resonance imaging. We found that the 28-h SD resulted in slower perceptual transitions in healthy individuals. The reduced perceptual transition was accompanied by the decreased activations in rivalry-related frontoparietal areas, including the right superior parietal lobule, right frontal eye field, and right temporoparietal junction. We speculated that SD might disrupt the normal function of these regions crucial for bistable perception, which mediated the slower rivalry-related perceptual transitions in behavior. Our findings revealed the neural changes underlying the abnormal bistable perception following the SD. It also suggested that SD might offer a new window to understand the neural mechanisms underlying the bistable perception.
Magnetic resonance current density imaging (MRCDI) can measure the magnetic fields created in the human brain from currents injected via surface electrodes. Previous methods have demonstrated high sensitivity sufficient for low current strengths (~1 mA). However, they have also proven susceptible to physiological noise. Here we increase the temporal resolution of the method and thereby the robustness to physiological noise by using echo-planar imaging (EPI) for the acquisition. We show that the method produces reliable magnetic field measurements with an average sensitivity of 52 pT for a 2 minutes scan with 3 mm isotropic resolution.
Abstract Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such as Rtn4r and Rgs7, and genes involved in membrane transport, such as Na + /K + ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of the vivo -seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.
The left inferior frontal gyrus (IFG) including Broca's area is involved in the processing of many language subdomains, and thus, research on the evolutional and human developmental characteristics of the left IFG will shed light on how language emerges and maturates. In this study, we used diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (fMRI) to investigate the evolutional and developmental patterns of the left IFG in humans (age 6–8, age 11–13, and age 16–18 years) and macaques. Tractography-based parcellation was used to define the subcomponents of left IFG and consistently identified four subregions in both humans and macaques. This parcellation scheme for left IFG in human was supported by specific coactivation patterns and functional characterization for each subregion. During evolution and development, we found increased functional balance, amplitude of low frequency fluctuations, functional integration, and functional couplings. We also observed higher fractional anisotropy values, i.e. better myelination of dorsal and ventral white matter language pathways during evolution and development. We assume that the resting-state functional connectivity and task-related coactivation mapping are associated with hierarchical language processing. Our findings have shown the evolutional and human developmental patterns of left IFG, and will contribute to the understanding of how the human language evolves and how atypical language developmental disorders may occur.
We examined the effects of number magnitude (within vs. outside the subitizable range) and notation (symbolic vs. nonsymbolic number) on neural responses to visual displays in the human brain using fMRI at 7T. We found that the right temporoparietal junction (rTPJ) responded more strongly to small than to larger numbers (2, 4 > 6, 8), while there was greater activity bilaterally within and around the intraparietal sulcus (IPS) as number magnitude increased (6, 8 > 2, 4). The effects of number magnitude were greatest for nonsymbolic stimuli. In addition, there was striking overlap between rTPJ regions responding to small numbers and those most strongly activated by symbolic stimuli, and between IPS regions responding to large numbers and those most activated by nonsymbolic stimuli. The results are consistent with distinct neural processes recruited for the processing of small- and large-number magnitudes. Contributions due to differences in representing exact number (small nonsymbolic arrays and all symbolic numbers, in rTPJ) and overall magnitude (particularly with large nonsymbolic arrays, in IPS), and the associated theoretical implications of the findings, are discussed.
Motivations of arterial spin labeling (ASL) at ultrahigh magnetic fields include prolonged blood T1 and greater signal-to-noise ratio (SNR). However, increased B0 and B1 inhomogeneities and increased specific absorption ratio (SAR) challenge practical ASL implementations. In this study, Turbo-FLASH (Fast Low Angle Shot) based pulsed and pseudo-continuous ASL sequences were performed at 7T, by taking advantage of the relatively low SAR and short TE of Turbo-FLASH that minimizes susceptibility artifacts. Consistent with theoretical predictions, the experimental data showed that Turbo-FLASH based ASL yielded approximately 4 times SNR gain at 7T compared to 3T. High quality perfusion images were obtained with an in-plane spatial resolution of 0.85×1.7 mm(2). A further functional MRI study of motor cortex activation precisely located the primary motor cortex to the precentral gyrus, with the same high spatial resolution. Finally, functional connectivity between left and right motor cortices as well as supplemental motor area were demonstrated using resting state perfusion images. Turbo-FLASH based ASL is a promising approach for perfusion imaging at 7T, which could provide novel approaches to high spatiotemporal resolution fMRI and to investigate the functional connectivity of brain networks at ultrahigh field.
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