Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery of circuit function and for engineered approaches to alleviate various disorders of the nervous system. However, evidence suggests that neural activity generated by artificial stimuli differs dramatically from normal circuit function, in terms of both the local neuronal population activity at the site of activation and the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. Here, we used voltage-sensitive dye imaging of primary somatosensory cortex in the anesthetized rat in response to deflections of the facial vibrissae and electrical or optogenetic stimulation of thalamic neurons that project directly to the somatosensory cortex. Although the different inputs produced responses that were similar in terms of the average cortical activation, the variability of the cortical response was strikingly different for artificial versus sensory inputs. Furthermore, electrical microstimulation resulted in highly unnatural spatial activation of cortex, whereas optical input resulted in spatial cortical activation that was similar to that induced by sensory inputs. A thalamocortical network model suggested that observed differences could be explained by differences in the way in which artificial and natural inputs modulate the magnitude and synchrony of population activity. Finally, the variability structure in the response for each case strongly influenced the optimal inputs for driving the pathway from the perspective of an ideal observer of cortical activation when considered in the context of information transmission.
SIGNIFICANCE STATEMENT Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery and clinical translation. However, neural activity generated by these artificial means differs dramatically from normal circuit function, both locally and in the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. The significance of this work is in quantifying the differences, elucidating likely mechanisms underlying the differences, and determining the implications for information processing.
A novel handheld probe based on a microelectromechanical systems (MEMS) scanning mirror for three-dimensional (3D) fluorescence molecular tomography (FMT) is described. The miniaturized probe consists of a MEMS mirror for delivering an excitation light beam to multiple preselected points at the tissue surface and an optical fiber array for collecting the fluorescent emission light from the tissue. Several phantom experiments based on indocyanine green, an FDA approved near-infrared (NIR) fluorescent dye, were conducted to assess the imaging ability of this device. Tumor-bearing mice with systematically injected tumor-targeted NIR fluorescent probes were scanned to further demonstrate the ability of this MEMS-based FMT for imaging small animals.
One dimensional Doppler Ultrasound (DUS) is a low cost method for fetal auscultation. However, accuracy of any metrics derived from the DUS signals depends on their quality, which relies heavily on operator skills. In low resource settings, where skill levels are sparse, it is important for the device to provide real time signal quality feedback to allow the re-recording of data. Retrospectively, signal quality assessment can help remove low quality recordings when processing large amounts of data. To this end, we proposed a novel template-based method, to assess DUS signal quality. Data used in this study were collected from 17 pregnant women using a low-cost transducer connected to a smart phone. Recordings were split into 1990 segments of 3.75 s duration, and hand labeled for quality by three independent annotators. The proposed template-based method uses Empirical Mode Decomposition (EMD) to allow detection of the fetal heart beats and segmentation into short, time-aligned temporal windows. Templates were derived for each 15 s window of the recordings. The DUS signal quality index (SQI) was calculated by correlating the segments in each window with the corresponding running template using four different pre-processing steps: (i) no additional preprocessing, (ii) linear resampling of each beat, (iii) dynamic time warping (DTW) of each beat and (iv) weighted DTW of each beat. The template-based SQIs were combined with additional features based on sample entropy and power spectral density. To assess the performance of the method, the dataset was split into training and test subsets. The training set was used to obtain the best combination of features for predicting the DUS quality using cross validation, and the test set was used to estimate the classification accuracy using bootstrap resampling. A median out of sample classification accuracy on the test set of 85.8% was found using three features; template-based SQI, sample entropy and the relative power in the 160 to 660 Hz range. The results suggest that the new automated method can reliably assess the DUS quality, thereby helping users to consistently record DUS signals with acceptable quality for fetal monitoring.
Translation of stem cell therapies to treat injuries and diseases of the spinal cord is hindered by lack of real-time monitoring techniques to guide regenerative therapies intra- and postoperatively. Thus, we developed an ultrasound (US), photoacoustic (PA), and magnetic resonance (MR) imaging approach augmented with Prussian blue nanocubes (PBNCs) to guide stem cell injections intraoperatively and monitor stem cell therapies in the spinal cord postoperatively. Per the clinical procedure, a multi-level laminectomy was performed in rats ex vivo, and PBNC-labeled stem cells were injected directly into the spinal cord while US/PA images were acquired. US/PA/MR images were also acquired post-surgery. Several features of the imaging approach were demonstrated including detection of low stem cell concentrations, real-time needle guidance and feedback on stem cell delivery, and good agreement between US/PA/MR images. These benefits span intra- and postoperative environments to support future development of this imaging tool.
This work reports the use of a head-motion monitoring system to record patient head movements while completing in-home exercises for vestibular rehabilitation therapy. Based upon a dual-axis gyroscope (yaw and pitch, ± 500-degrees/sec maximum), angular head rotations were measured and stored via an on-board memory card. The system enabled the clinician to document exercises at home. Several measurements were recorded in one patient with unilateral vestibular hypofunction: The total time of exercise for the week (118 minutes) was documented and compared with expected weekly exercise time (140 minutes). For gaze stabilization exercises, execution time of 60 sec was expected, and observed times ranged from 75-100 sec. An absence of rest periods between each exercise instead of the recommended one minute rest period was observed. Maximum yaw head velocities from approximately 100-350 degrees/sec were detected. A second subject provided feedback concerning the ease of use of the HAMMS device. This pilot study demonstrates, for the first time, the capability to capture the head-motion "signature" of a patient while completing vestibular rehabilitation exercises in the home and to extract exercise regime parameters and monitor patient adherence. This emerging technology has the potential to greatly improve rehabilitation outcomes for individuals completing in-home gaze stabilization exercises.
Ternary chalcopyrite CuInS2 quantum dots (QDs) have been extensively studied in recent years as an alternative to conventional QDs for solar energy conversion applications. However, compared with the well-established photophysics in prototypical CdSe QDs, much less is known about the excited properties of CuInS2 QDs. In this work, using ultrafast spectroscopy, we showed that both conduction band (CB) edge electrons and copper vacancy (VCu) localized holes were susceptible to surface trappings in CuInS2 QDs. These trap states could be effectively passivated by forming quasi-type II CuInS2/CdS core/shell QDs, leading to a single-exciton (with electrons delocalized among CuInS2/CdS CB and holes localized in VCu) half lifetime of as long as 450 ns. Because of reduced electron-hole overlap in quasi-type II QDs, Auger recombination of multiple excitons was also suppressed and the bi-exciton lifetime was prolonged to 42 ps in CuInS2/CdS QDs from 10 ps in CuInS2 QDs. These demonstrated advantages, including passivated trap states, long single and multiple exciton lifetimes, suggest that quasi-type II CuInS2/CdS QDs are promising materials for photovoltaic and photocatalytic applications.
Contrast-enhanced ultrasound imaging utilizing the nonlinear responses of microbubbles is proposed for identifying ventricular shunt malfunction. The developed method suppresses the signal from walls of a shunt catheter and background tissues, and allows accurate measurements of the cerebrospinal fluid flow within the shunt catheter using a relatively small concentration of microbubbles. The flow rates estimated in the linear mode were significantly underestimated (65% at 0.1ml/min and 5.0% microbubble concentration) while estimates using the nonlinear mode were not. Overall, the nonlinear responses of microbubbles improve the estimation of flow rates in a shunt catheter at low concentrations of microbubbles.
Purpose: This study introduces a real-time contrast-enhanced ultrasound imaging method with recently developed laser-activated nanodroplets (LANDs), a new class of phase-change nanometer-scale contrast agents that provides perceptible, sustained high-contrast with ultrasound. Methods: In response to pulsed laser irradiation, the LANDs -, which contain liquid perfluorohexane and optical fuses - blink (vaporize and recondense). That is, they change their state from liquid nanodroplets to gas microbubbles, and then back to liquid nanodroplets. In their gaseous microbubble state, the LANDs provide high-contrast ultrasound, but the microbubbles formed in situ typically recondense in tens of milliseconds. As a result, LAND visualization by standard, real-time ultrasound is limited. However, the periodic optical triggering of LANDs allows us to observe corresponding transient, periodic changes in ultrasound contrast. This study formulates a probability function that measures how ultrasound temporal signals vary in periodicity. Then, the estimated probability is mapped onto a B-scan image to construct a LAND-localized, contrast-enhanced image. We verified our method through phantom and in vivo experiments using an ultrasound system (Vevo 2100, FUJIFILM VisualSonics, Inc., Toronto, ON, Canada) operating with a 40-MHz linear array and interfaced with a 10 Hz Nd:YAG laser (Phocus, Opotek Inc., Carlsbad, CA, USA) operating at the fundamental 1064 nm wavelength. Results: From the phantom study, the results showed improvements in the contrast-to-noise ratio of our approach over conventional ultrasound ranging from 129% to 267%, with corresponding execution times of 0.10 to 0.29 s, meaning that the developed method is computationally efficient while yielding high-contrast ultrasound. Furthermore, in vivo sentinel lymph node (SLN) imaging results demonstrated that our technique could accurately identify the SLN. Conclusions: The results indicate that our approach enables efficient and robust LAND localization in real time with substantially improved contrast, which is essential for the successful translation of this contrast agent platform to clinical settings.
The BOLD signal reflects hemodynamic events within the brain, which in turn are driven by metabolic changes and neural activity. However, the link between BOLD changes and neural activity is indirect and can be influenced by a number of non-neuronal processes. Motion and physiological cycles have long been known to affect the BOLD signal and are present in both humans and animal models. Differences in physiological baseline can also contribute to intra- and inter-subject variability. The use of anesthesia, common in animal studies, alters neural activity, vascular tone, and neurovascular coupling. Most intriguing, perhaps, are the contributions from other processes that do not appear to be neural in origin but which may provide information about other aspects of neurophysiology. This review discusses different types of noise and non-neuronal contributors to the BOLD signal, sources of variability for animal studies, and insights to be gained from animal models.
Background The aim of this study was to noninvasively measure regional contributions of vasculature in the human body using magnetohydrodynamic voltages (V MHD ) obtained from electrocardiogram (ECG) recordings performed inside MRI’s static magnetic field (B 0 ). Integrating the regional V MHD over the S wave -T wave segment of the cardiac cycle (V segment ) provides a noninvasive method for measuring regional blood volumes, which can be rapidly obtained during MRI without incurring additional cost. Methods V MHD was extracted from 12-lead ECG traces acquired during gradual introduction into a 3T MRI. Regional contributions were computed utilizing weights based on B 0 ’s strength at specified distances from isocenter. V segment mapping was performed in six subjects and validated against MR angiograms (MRA). Results Fluctuations in V segment , which presented as positive trace deflections, were found to be associated with aortic-arch flow in the thoracic cavity, the main branches of the abdominal aorta, and the bifurcation of the common iliac artery. The largest fluctuation corresponded to the location where the aortic arch was approximately orthogonal to B 0 . The smallest fluctuations corresponded to areas of vasculature that were parallel to B 0 . Significant correlations (specifically, Spearman’s ranked correlation coefficients of 0.96 and 0.97 for abdominal and thoracic cavities, respectively) were found between the MRA and V segment maps (p < 0.001). Conclusions A novel non-invasive method to extract regional blood volumes from ECGs was developed and shown to be a rapid means to quantify peripheral and abdominal blood volumes.