Analysis of the robustness and dynamics of spin-locking preparations for the detection of oscillatory magnetic fields.

Extracting quantitative information of neuronal signals by non-invasive imaging is an outstanding challenge for understanding brain function and pathology. However, state-of-the-art techniques offer low sensitivity to deep electrical sources. Stimulus induced rotary saturation is a recently proposed magnetic resonance imaging sequence that detects oscillatory magnetic fields using a spin-lock preparation. Phantom experiments and simulations proved its efficiency and sensitivity, but the susceptibility of the method to field inhomogeneities is still not well understood. In this study, we simulated and analyzed the dynamic of three spin-lock preparations and their response to field inhomogeneities in the presence of a resonant oscillating field. We show that the composite spin-lock preparation is more robust against field variations within the double resonance effect. In addition, we tested the capability of the chosen composite spin-lock preparation to recover information about the spectral components of a composite signal. This study sets the bases to move one step further towards the clinical application of MR-based neuronal current imaging

Detecting diverse types of cardiovascular brain pulses in Alzheimer’s disease simultaneously with fNIRS and MREG

Abstract. One of the risk factors for Alzheimer’s disease is hypertension. Hypertension alters the brain’s blood vessel structure due to increased arterial pressure. Structural changes in the blood vessels are seen in the cardiovascular pulse, which is formed by blood velocity, blood flow rate, blood pressure, and infrequently blood flow. By simultaneously applying magnetic resonance encephalography (MREG) and functional near-infrared spectroscopy (fNIRS), this study discovered cardiovascular brain pulses from the blood flow within patients with Alzheimer’s disease and healthy controls. This study detects specific parameters within diverse types of cardiovascular brain pulses. The results detected changes in parameters for diverse types of cardiovascular brain pulses in patients with Alzheimer’s disease within MREG and fNIRS. In addition, the results present an alternative method for finding cardiovascular brain pulse from the blood flow, which might reflect the structural changes of a blood vessel in patients with Alzheimer’s disease. In conclusion, diverse types of cardiovascular brain pulses represent an approximation of arterial, venous, and tissue pulses, which is beneficial for distinguishing the effect of venous and arterial hypertension in Alzheimer’s disease. Furthermore, altered blood flow may potentially be associated with the impaired glymphatic system in Alzheimer’s disease

Silicon photomultiplier based continuous-wave functional near-infrared spectroscopy module with multi-distance measurements

In recent years, there has been growing interest in developing fiberless and wireless functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT) instruments. However, developing such instruments poses multiple challenges, interms of cost, safety, system complexity and achievable signal quality. One crucial factor in developing wireless and fiberless instruments is the appropriate choice of detectors. Currently, the majority of existing wireless and/or fiberless systems use photodiodes due to their low cost and low power requirements. However, under low-light conditions, the SNR of photodiodes diminishes significantly, making them less effective for measurements with long source–detector separations. The silicon photomultiplier (SiPM) is a relatively new type of detector that contains high internal amplification; this makes SiPMs suitable for low-light applications. Although SiPMs can increase signal quality at long source–detector distances, they cost more and have higher power requirements than photodiodes. This thesis presents the design of a multi-distance, multichannel DOT prototype that uses a hybrid detector arrangement. This arrangement uses photodiodes for short-distance measurements (i.e., 1 cm) and silicon photomultipliers for long-distance measurements (i.e., 3 cm and 4.5 cm). The developed system consists of two printed circuit boards (PCBs): a DOT sensor PCB, a data acquisition and control PCB as well as a graphical user interface. The performance of the developed DOT system prototype was validated using a dynamic optical phantom. The results show that the prototype works as intended

Methods for functional brain imaging

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2011.Cataloged from PDF version of thesis.Includes bibliographical references.Magnetic resonance imaging (MRI) has demonstrated the potential for non-invasive mapping of structure and function (fMRI) in the human brain. In this thesis, we propose a series of methodological developments towards improved fMRI of auditory processes. First, the inefficiency of standard fMRI that acquires brain volumes one slice at a time is addressed. The proposed single-shot method is capable, for the first time, of imaging the entire brain in a single-acquisition while still maintaining adequate spatial resolution for fMRI. This method dramatically increases the temporal resolution of fMRI (20 fold) and improves sampling efficiency as well as the ability to discriminate against detrimental physiological noise. To accomplish this it exploits highly accelerated parallel imaging techniques and MRI signal detection with a large number of coil elements. We then address a major problem in the application of fMVIRI to auditory studies. In standard fMRI, loud acoustic noise is generated by the rapid switching of the gradient magnetic fields required for image encoding, which interferes with auditory stimuli and enforces inefficient and slow sampling strategies. We demonstrate a fMRI method that uses parallel imaging and redesigned gradient waveforms to both minimize and slow down the gradient switching to substantially reduce acoustic noise while still enabling rapid acquisitions for fMRI. Conventional fMRI is based on a hemodynamic response that is secondary to the underlying neuronal activation. In the final contribution of this thesis, a novel image contrast is introduced that is aimed at the direct observation of neuronal magnetic fields associated with functional activation. Early feasibility studies indicate that the imaging is sensitive to oscillating magnetic fields at amplitudes similar to those observed by magnetoencephalography.by Thomas Witzel.Ph.D

Expanding the role of functional mri in rehabilitation research

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) contrast has become a universal methodology in functional neuroimaging. However, the BOLD signal consists of a mix of physiological parameters and has relatively poor reproducibility. As fMRI becomes a prominent research tool for rehabilitation studies involving repeated measures of the human brain, more quantitative and stable fMRI contrasts are needed. This dissertation enhances quantitative measures to complement BOLD fMRI. These additional markers, cerebral blood flow (CBF) and cerebral blood volume (CBV) (and hence cerebral metabolic rate of oxygen (CMRO₂) modeling) are more specific imaging markers of neuronal activity than BOLD. The first aim of this dissertation assesses feasibility of complementing BOLD with quantitative fMRI measures in subjects with central visual impairment. Second, image acquisition and analysis are developed to enhance quantitative fMRI by quantifying CBV while simultaneously acquiring CBF and BOLD images. This aim seeks to relax assumptions related to existing methods that are not suitable for patient populations. Finally, CBF acquisition using a low-cost local labeling coil, which improves image quality, is combined with simultaneous acquisition of two types of traditional BOLD contrast. The demonstrated enhancement of CBF, CBV and CMRO₂measures can lead to better characterization of pathophysiology and treatment effects.Ph.D.Committee Chair: Hu, Xiaoping; Committee Member: Benkeser, Paul; Committee Member: Keilholz, Shella; Committee Member: Sathian, Krish; Committee Member: Schuchard, Ronal

Connectivity of the Primate Superior Colliculus Mapped by Concurrent Microstimulation and Event-Related fMRI

Background: Neuroanatomical studies investigating the connectivity of brain areas have heretofore employed procedures in which chemical or viral tracers are injected into an area of interest, and connected areas are subsequently identified using histological techniques. Such experiments require the sacrifice of the animals and do not allow for subsequent electrophysiological studies in the same subjects, rendering a direct investigation of the functional properties of anatomically identified areas impossible. Methodology/Principal Findings: Here, we used a combination of microstimulation and fMRI in an anesthetized monkey preparation to study the connectivity of the superior colliculus (SC). Microstimulation of the SC resulted in changes in the blood oxygenation level-dependent (BOLD) signals in the SC and in several cortical and subcortical areas consistent with the known connectivity of the SC in primates. Conclusions/Significance: These findings demonstrates that the concurrent use of microstimulation and fMRI can be used to identify brain networks for further electrophysiological or fMRI investigation

Streamlining the Design and Use of Array Coils for In Vivo Magnetic Resonance Imaging of Small Animals

Small-animal models such as rodents and non-human primates play an important pre-clinical role in the study of human disease, with particular application to cancer, cardiovascular, and neuroscience models. To study these animal models, magnetic resonance imaging (MRI) is advantageous as a non-invasive technique due to its versatile contrast mechanisms, large and flexible field of view, and straightforward comparison/translation to human applications. However, signal-to-noise ratio (SNR) limits the practicality of achieving the high-resolution necessary to image the smaller features of animals in an amount of time suitable for in vivo animal MRI. In human MRI, it is standard to achieve an increase in SNR through the use of array coils; however, the design, construction, and use of array coils for animal imaging remains challenging due to copper-loss related issues from small array elements and design complexities of incorporating multiple elements and associated array hardware in a limited space. In this work, a streamlined strategy for animal coil array design, construction, and use is presented and the use for multiple animal models is demonstrated. New matching network circuits, materials, assembly techniques, body-restraining systems and integrated mechanical designs are demonstrated for streamlining high-resolution MRI of both anesthetized and awake animals. The increased SNR achieved with the arrays is shown to enable high-resolution in vivo imaging of mice and common marmosets with a reduced time for experimental setup

Cortical Layer-Dependent Hemodynamic Regulation Investigated by Functional Magnetic Resonance Imaging

Functional magnetic resonance imaging (fMRI) is currently one of the most widely used non-invasive neuroimaging modalities for mapping brain activation. Techniques such as blood oxygenation level dependent (BOLD) fMRI or cerebral blood volume (CBV)-weighted fMRI are based on the assumption that hemodynamic responses are tightly regulated by neural activity. However, the relationship between fMRI responses and neural activity is still unclear. To investigate this relationship, the unique properties of temporal frequency tuning of primary visual cortex neurons was used as a model since it can be used to separate the neural input and output activities of this area. During moving grating stimuli of 1, 2, 10 and 20 Hz temporal frequencies, two fMRI studies, areal and laminar studies, were conducted with different spatial resolution in a 9.4-T Varian spectrometer. In areal studies, BOLD fMRI was able to detect the difference in tuning properties between area 17 (A17), area 18 (A18) and lateral geniculate nucleus. In A17, the BOLD tuning curve seemed to reflect the local field potential (LFP) low frequency band (<12 Hz) rather than spiking activity and LFP gamma band (25-90 Hz). In laminar studies, a high spatial resolution protocol was adopted to resolve the different cortical layers in A17. In addition to BOLD fMRI, CBV-weighted fMRI was performed to eliminate the contamination from the superficial draining veins. These results showed that BOLD and CBV tuning curves do not reflect the underlying spiking activity or the LFP activity at infragranular layers (the bottom layer of three cortical layers). This implies that the hemodynamic response may not be regulated on a laminar level. Therefore, caution should be taken when interpreting BOLD responses as the sole indicator of different aspects of neural activity in areal and laminar scales