Adaptive functional MRI

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 2000.Some research performed with the Harvard-M.I.T. Division of Health Sciences and Technology.Includes bibliographical references (leaves 132-140).Functional MRI (fMRI) detects the signal associated with neuronal activation, and has been widely used to map brain functions. Locations of neuronal activation are localized and distributed throughout the brain, however, conventional encoding methods based on k-space acquisition have limited spatial selectivity. To improve it, we propose an adaptive fMRI method using non-Fourier, spatially selective RF encoding. This method follows a strategy of zooming into the locations of activation by progressively eliminating the regions that do not show any apparent activation. In this thesis, the conceptual design and implementation of adaptive fMRI are pursued under the hypothesis that the method may provide a more efficient means to localize functional activities with increased spatial or temporal resolution. The difference between functional detection and mapping is defined, and the multi- resolution approach for functional detection is examined using theoretical models simulating variations in both in-plane and through-plane resolution. We justify the multi-resolution approach experimentally using BOLD CNR as a quantitative measure and compare results to those obtained using theoretical models. We conclude that there is an optimal spatial resolution to obtain maximum detection; when the resolution matches the size of the functional activation. We demonstrated on a conventional 1.5-Tesla system that RF encoding provides a simple means for monitoring irregularly distributed slices throughout the brain without encoding the whole volume. We also show the potential for increased signal-to-noise ratio with Hadamard encoding as well as reduction of the in-flow effect with unique design of excitation pulses.(cont.) RF encoding was further applied in the implementation of real-time adaptive fMRI method, where we can zoom into the user-defined regions interactively. In order to do so, real-time pulse prescription and data processing capabilities were combined with RF encoding. Our specific implementation consisted of five scan stages tailored to identify the volume of interest, and to increase temporal resolution (from 7.2 to 3.2 seconds) and spatial resolution (from 10 mm to 2.5-mm slice thickness). We successfully demonstrated the principle of the multi- resolution adaptive fMRI method in volunteers performing simple sensorimotor paradigms for simultaneous activation of primary motor as well as cerebellar areas.by Seung-Schik Yoo.Ph.D

Estimation of the spatial profile of neuromodulation and the temporal latency in motor responses induced by focused ultrasound brain stimulation

This study investigates the spatial profile and the temporal latency of the brain stimulation induced by the transcranial application of pulsed focused ultrasound (FUS). The site of neuromodulation was detected using 2-deoxy-2-[18F]fluoro-d-glucose PET immediately after FUS sonication on the unilateral thalamic area of Sprague–Dawley rats. The latency of the stimulation was estimated by measuring the time taken from the onset of the stimulation of the appropriate brain motor area to the corresponding tail motor response. The brain area showing elevated glucose uptake from the PET image was much smaller (56±10% in diameter, 24±6% in length) than the size of the acoustic focus, which is conventionally defined by the full-width at half-maximum of the acoustic intensity field. The spatial dimension of the FUS-mediated neuromodulatory area was more localized, approximated to be full-width at 90%-maximum of the acoustic intensity field. In addition, the time delay of motor responses elicited by the FUS sonication was 171±63 (SD) ms from the onset of sonication. When compared with latencies of other nonultrasonic neurostimulation techniques, the longer time delay associated with FUS-mediated motor responses is suggestive of the nonelectrical modes of neuromodulation, making it a distinctive brain stimulation method

Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain functionopen43

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity

<p>Abstract</p> <p>Background</p> <p>Epilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ).</p> <p>Results</p> <p>After the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm²) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue.</p> <p>Conclusions</p> <p>These results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.</p

Engineered 3D tissue models for cell-laden microfluidic channels

Abstract Delivery of nutrients and oxygen within threedimensional (3D) tissue constructs is important to maintain cell viability. We built 3D cell-laden hydrogels to validate a new tissue perfusion model that takes into account nutrition consumption. The model system was analyzed by simulating theoretical nutrient diffusion into cell-laden hydrogels. We carried out a parametric study considering different microchannel sizes and inter-channel separation in the hydrogel. We hypothesized that nutrient consumption needs to be taken into account when optimizing the perfusion channel size and separation. We validated the hypothesis by experiments. We fabricated circular microchannels (r= 400 μm) in 3D cell-laden hydrogel constructs (R = 7.5 mm, volume=5 ml). These channels were positioned either individually or in parallel within hydrogels to increase nutrient and oxygen transport as a way to improve cell viability. We quantified the spatial distribution of viable cells within 3D hydrogel scaffolds without channels and with single-and dual-perfusion microfluidic channels. We investigated quantitatively the cell viability as a function of radial distance from the channels using experimental data and mathematical modeling of diffusion profiles. Our simulations show that a large-channel radius as well as a large channel to channel distance diffuse nutrients farther through a 3D hydrogel. This is important since our results reveal that there is a close correlation between nutrient profiles and cell viability across the hydrogel

Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0 +/- 3.0% accuracy, with a time delay of 1.59 +/- 1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.open12

Pulsed application of focused ultrasound to the LI4 elicits deqi sensations: Pilot study

Objectives: Focused ultrasound (FUS) techniques enable the delivery of acoustic pressure waves to a localized, specific region of anatomy, and mechanically stimulate the sonicated region when given in a train of pulses. The present pilot study examines if the pulsed application of acoustic waves focused to an acupuncture point ( LI4, Hegu), i.e. FUS acupuncture, can elicit deqi sensations. Design and setting: The FUS was generated by a single-element ultrasound transducer, and delivered to the LI4 of acupuncture-naive participants (n =10) for a duration of 1s using 2ms tone-burst-duration and 50Hz pulse repetition frequency. The subjective ratings of deqi descriptors were obtained across different conditions, i.e. FUS acupuncture using acoustic intensities of 1 and 3W/cm2 (spatial-peak temporal-averaged intensity, I spta), sham sonication condition, tactile stimulation using a von Frey monofilament, and needle-based real and sham acupuncture. We also measured the presence of sharp pain, unpleasantness, and anxiety level during each condition. Results: The FUS acupuncture given at 3W/cm2 elicited deqi sensation ratings similar to those acquired during the needle-based acupuncture condition across the subjects, with significantly reduced levels of non-deqi related sensations, such as sharp pain, anxiety and unpleasantness. The lower acoustic intensity also generated deqi sensations, but at a lesser degree than the ones acquired using the higher acoustic intensity. Neither the sham conditions nor the tactile stimulation elicited deqi sensations. Conclusions: The present data on acoustic acupuncture, with its exquisite spatial and depth control, along with the ability to electronically adjust its intensity, may suggest its potential utilization as an alternative mode of acupuncture, although further study is needed to probe its clinical efficacy.close0

Cerebrospinal fluid solute transport associated with sensorimotor brain activity in rodents

Abstract Cerebrospinal fluid (CSF) is crucial for maintaining neuronal homeostasis, providing nutrition, and removing metabolic waste from the brain. However, the relationship between neuronal activity and CSF solute transport remains poorly understood. To investigate the effect of regional neuronal activity on CSF solute transport, Sprague–Dawley rats (all male, n = 30) under anesthesia received an intracisternal injection of a fluorescent tracer (Texas Red ovalbumin) and were subjected to unilateral electrical stimulation of a forelimb. Two groups (n = 10 each) underwent two different types of stimulation protocols for 90 min, one including intermittent 7.5-s resting periods and the other without rest. The control group was not stimulated. Compared to the control, the stimulation without resting periods led to increased transport across most of the cortical areas, including the ventricles. The group that received intermittent stimulation showed an elevated level of solute uptake in limited areas, i.e., near/within the ventricles and on the ventral brain surface. Interhemispheric differences in CSF solute transport were also found in the cortical regions that overlap with the forelimb sensorimotor area. These findings suggest that neuronal activity may trigger local and brain-wide increases in CSF solute transport, contributing to waste clearance