Biology subjects

Wald, L. L.

Publications and source records attributed to Wald, L. L..

At least 19 recordsLinked to original sources

bioRxiv2026

Peripheral Nerve Stimulation Optimized Pulses for EPI (POPE) allows high-resolution fMRI

PurposeRecent improvements in MRI gradient design and amplifiers, advanced MRI scanners are now routinely utilizing slew rates of several hundred T/m/s. However, full gradient performance cannot be exploited in high-resolution EPI due to peripheral nerve stimulation (PNS) limits. We aim to characterize and mitigate these PNS constraints using a simple sequence modification: PNS-optimized EPI gradient pulse shapes. MethodsPNS-Optimized Pulses for EPI (POPE): we selectively reduce the slew rate of gradient pulses at periods of high predicted PNS spikes, while leaving the rest of the waveform unchanged. PNS sensation was evaluated. ResultsPOPE allows 7%-35% faster imaging of EPI protocols resolutions of 1mm-0.3mm resolutions without exceeding predicted PNS. With such improvements, POPE allows robust 0.3 mm isotropic fMRI protocols that would have exceeded safety limits without it. ConclusionPOPE facilitates locally precise fMRI activation mapping on clinical 7T scanners at spatial resolution that were previously unattainable due to PNS limitations.

neuroscience↗

bioRxiv2026

Neural activity drives directional subarachnoid cerebrospinal fluid flow in the human brain

Neural activity is a potential driver of cerebrospinal fluid (CSF) dynamics and brain waste clearance, yet how neural activity shapes localized CSF flow in the subarachnoid space remains poorly understood in humans. Here we introduce an MRI framework that enables concurrent mapping of ultra-slow subarachnoid CSF flow at velocity scales of tens of micrometers-per-second together with hemodynamic activity measured by simultaneous functional MRI in the human brain. Using this framework, we found that neural activity drives spatiotemporally coherent, directional CSF flow in the subarachnoid space near sites of neural activation in awake humans. These flow responses were highly spatially specific, shaped by local cortical and subarachnoid anatomy, while exhibiting oscillatory temporal dynamics modulated by the stimulus cycle and strongly coupled to hemodynamic responses. These findings establish a link between neural activity, vascular dynamics, and localized subarachnoid CSF flow, and provide a framework for investigating neural-activity-driven CSF transport in humans.

neuroscience↗

bioRxiv2026

Mapping subarachnoid cerebrospinal fluid circulation in the human brain

The subarachnoid space is critical to cerebrospinal fluid (CSF) circulation and waste clearance, yet its flow organization in humans remains poorly characterized due to the lack of methods for direct, quantitative measurement of ultra-slow flow. Here we introduce slow-flow-sensitized phase-contrast imaging (SOPHI), which enables noninvasive quantification of ultra-slow flow velocities (e.g., [~]100 m/s) and directionality at high spatiotemporal resolution, allowing whole-brain mapping of complex CSF circulation in the human subarachnoid space. We found brain-wide, spatiotemporally coherent flow patterns characterized by strong cardiac-driven oscillations. Flow dynamics were closely coupled with vascular anatomy, exhibiting higher velocities and earlier responses in subarachnoid spaces near major arteries and a spatiotemporal propagative pattern to distal spaces. We further identified localized flow pathways associated with potential CSF efflux in ventricles and key subarachnoid regions. Together, SOPHI reveals a previously undercharacterized, highly organized CSF flow system, providing a macroscopic view of human CSF circulation and a framework for investigating brain fluid transport.

bioengineering↗

bioRxiv2025

Quantifying brain-wide cerebrospinal fluid flow dynamics using slow-flow-sensitized phase-contrast MRI

Cerebrospinal fluid (CSF) flow is a key component of the brains waste clearance system. However, our understanding of CSF flow in the human brain, particularly within the brain-wide subarachnoid space (SAS), is limited due to a lack of non-invasive tools for measuring slow flow. Here, we propose a CSF flowmetry technique using phase-contrast MRI combined with a slow-flow-sensitized acquisition. It achieves high sensitivity in measuring slow CSF flow (e.g., 100 m/s), and enables quantitative measurement of the velocity and direction with whole-brain coverage, spanning from ventricles to SAS. Our proof-of-concept results demonstrate repeatable flow measurements and show that cardiac pulsation induces coherent CSF flow changes within the SAS. Our data also suggest that cardiac pulsation has a stronger driving effect on brain-wide CSF flow compared to respiration. This technique provides a valuable tool for investigating CSF dynamics and pathways to advance a holistic understanding of brain-wide CSF flow. TeaserA novel MR technique enables noninvasive, quantitative mapping of slow cerebrospinal fluid flow in the subarachnoid space across the human brain.

bioengineering↗

bioRxiv2024

Romer-EPTI: Rotating-view motion-robust super-resolution EPTI for SNR-efficient distortion-free in-vivo mesoscale dMRI and microstructure imaging

PurposeTo overcome the major challenges in dMRI acquisition, including low SNR, distortion/blurring, and motion vulnerability. MethodsA novel Romer-EPTI technique is developed to provide distortion-free dMRI with significant SNR gain, high motion-robustness, sharp spatial resolution, and simultaneous multi-TE imaging. It introduces a ROtating-view Motion-robust supEr-Resolution technique (Romer) combined with a distortion/blurring-free EPTI encoding. Romer enhances SNR by a simultaneous multi-thick-slice acquisition with rotating-view encoding, while providing high motion-robustness through a motion-aware super-resolution reconstruction, which also incorporates slice-profile and real-value diffusion, to resolve high-isotropic-resolution volumes. The in-plane encoding is performed using distortion/blurring-free EPTI, which further improves effective spatial resolution and motion robustness by preventing not only T2/T2*-blurring but also additional blurring resulting from combining encoded volumes with inconsistent geometries caused by dynamic distortions. Self-navigation was incorporated to enable efficient phase correction. Additional developments include strategies to address slab-boundary artifacts, achieve minimal TE for SNR gain at 7T, and achieve high robustness to strong phase variations at high b-values. ResultsUsing Romer-EPTI, we demonstrate distortion-free whole-brain mesoscale in-vivo dMRI at both 3T (500-m-iso) and 7T (485-m-iso) for the first time, with high SNR efficiency (e.g., [Formula]), and high image quality free from distortion and slab-boundary artifacts with minimal blurring. Motion experiments demonstrate Romer-EPTIs high motion-robustness and ability to recover sharp images in the presence of motion. Romer-EPTI also demonstrates significant SNR gain and robustness in high b-value (b=5000s/mm2) and time-dependent dMRI. ConclusionRomer-EPTI significantly improves SNR, motion-robustness, and image quality, providing a highly efficient acquisition for high-resolution dMRI and microstructure imaging.

bioengineering↗

bioRxiv2024

Single-shot Echo Planar Time-resolved Imaging for multi-echo functional MRI and distortion-free diffusion imaging

PurposeTo develop EPTI, a multi-shot distortion-free multi-echo imaging technique, into a single-shot acquisition to achieve improved robustness to motion and physiological noise, increased temporal resolution, and high SNR efficiency for dynamic imaging applications. MethodsA new spatiotemporal encoding was developed to achieve single-shot EPTI by enhancing spatiotemporal correlation in k-t space. The proposed single-shot encoding improves reconstruction conditioning and sampling efficiency, with additional optimization under various accelerations to achieve optimized performance. To achieve high SNR efficiency, continuous readout with minimized deadtime was employed that begins immediately after excitation and extends for an SNR-optimized length. Moreover, k-t partial Fourier and simultaneous multi-slice acquisition were integrated to further accelerate the acquisition and achieve high spatial and temporal resolution. ResultsWe demonstrated that ss-EPTI achieves higher tSNR efficiency than multi-shot EPTI, and provides distortion-free imaging with densely-sampled multi-echo images at resolutions [~]1.25-3 mm at 3T and 7T-- with high SNR efficiency and with comparable temporal resolutions to ss-EPI. The ability of ss-EPTI to eliminate dynamic distortions common in EPI also further improves temporal stability. For fMRI, ss-EPTI also provides early-TE images (e.g., 2.9ms) to recover signal-intensity and functional-sensitivity dropout in challenging regions. The multi-echo images provide TE-dependent information about functional fluctuations, successfully distinguishing noise-components from BOLD signals and further improving tSNR. For diffusion MRI, ss-EPTI provides high-quality distortion-free diffusion images and multi-echo diffusion metrics. Conclusionss-EPTI provides distortion-free imaging with high image quality, rich multi-echo information, and enhanced efficiency within comparable temporal resolution to ss-EPI, offering a robust and efficient acquisition for dynamic imaging.

bioengineering↗

bioRxiv2023

Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain: replication and extension with 7 Tesla fMRI

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, called allostasis. In support of allostasis, the brain continually models the sensory state of the body, called interoception. We replicated and extended a large-scale system supporting allostasis and interoception in the human brain using ultra-high precision 7 Tesla functional magnetic resonance imaging (fMRI) (N = 90), improving the precision of subgenual and pregenual anterior cingulate topography combined with extensive brainstem nuclei mapping. We observed over 90% of the anatomical connections published in tract-tracing studies in non-human animals. The system also included regions of dense intrinsic connectivity broadly throughout the system, some of which were identified previously as part of the backbone of neural communication across the brain. These results strengthen previous evidence for a whole-brain system supporting the modeling and regulation of the internal milieu of the body.

neuroscience↗

bioRxiv2023

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 coil solutions for ultra-high field imaging; however, very few commercial and research 7 Tesla radiofrequency coils currently exist for the spinal cord, and in particular those with parallel transmit 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 8 dipoles to ensure high homogeneity over this large region of the spinal cord. The Rx portion is made of 20 semi-adaptable 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 being tight fitting to ensure high sensitivity. We demonstrate RF shimming capabilities to optimize B1+ uniformity, power efficiency and/or specific absorption rate (SAR) efficiency. B1+ homogeneity, SNR and g-factor was 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.

bioengineering↗

bioRxiv2022

Distinct spatial patterns of neural and physiology-related activity in the human periaqueductal grey during anticipatory social stress.

Periaqueductal gray (PAG) columns mediate affective experience, physiological regulation, and survival-related behavior; yet, only 7T imaging can resolve these small structures in humans. In a social stress task, participants prepared a speech, and we observed (a) bilateral ventrolateral PAG activity, relative to baseline, and (b) distinct spatial patterns of correlation between PAG activity and physiological response (i.e., cardiac interbeat interval, reparation rate, and tonic electrodermal activity).

neuroscience↗

bioRxiv2022

7-Tesla evidence for columnar and rostral--caudal organization of the human periaqueductal grey response in the absence of threat: a working memory study

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high field 7-Tesla fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function in humans during a working memory task (N = 87). Relative to baseline fixation, both mild and moderate task-elicited cognitive demands elicited bilateral BOLD increases in ventrolateral PAG (vlPAG), a region previously observed to show increased activity during anticipated painful threat in both non-human and human animals. The present task posed only the most minimal (if any) "threat". The mild-demand condition involved a task easier than remembering a phone number, elicited a heart rate decrease relative to baseline, yet nonetheless elicited a bilateral vlPAG response. Across PAG voxels, BOLD signal intensity correlated with changes in physiological reactivity (relative to baseline) and showed some evidence of spatial organization along the rostral-caudal axis. These findings suggest that the PAG may have a broader role in coordinating brain--body communication during a minimally to moderately demanding task, even in the absence of threat.

neuroscience↗

bioRxiv2022

The role of human superior colliculus in affective experiences during visual and somatosensory stimulation

The superior colliculus is often studied for its role in visually guided behaviors, but research in non-human animals indicates it is a midbrain hub for processing sensory information from multiple domains, including interoception (which is associated with affect). We used ultra-high field 7-Tesla fMRI to extend this work to humans, modeling superior colliculus BOLD signal intensity during visual or somatosensory stimulation (N = 40 in each sensory modality), both under aversive and neutral affective intensity. As hypothesized, the superior colliculus showed increased BOLD signal intensity in the dorsal and ventral subregions during visual and somatosensory stimulation, respectively. The entire superior colliculus also showed increased BOLD signal intensity during aversive compared to neural conditions. The superior colliculus BOLD signal intensity also correlated with a preregistered set of brain regions involved in visual, somatosensory, and interoceptive processing.

neuroscience↗

bioRxiv2022

Layer-dependent activity in the human superior colliculus during working memory

We examined the superior colliculus (SC) with ultra-high resolution 7-Tesla fMRI during an N-back working memory task. We observed both increased BOLD signal intensity and functional connectivity that followed a layer-dependent pattern predicted from anatomical connections between SC and other brain structures important for visual processing, motor control, and executive function. Our results highlight a role for the human SC in cognitive functions that usually associated with the cerebral cortex.

neuroscience↗

bioRxiv2021

SNR-efficient distortion-free diffusion relaxometry imaging using ACcelerated Echo-train shifted EPTI (ACE-EPTI)

PurposeTo develop an efficient acquisition technique for distortion-free diffusion MRI and diffusion-relaxometry. MethodsA new ACcelerated Echo-train shifted Echo-Planar Time-resolved Imaging (ACE-EPTI) technique is developed to achieve high-SNR, distortion- and blurring-free diffusion and diffusion-relaxometry imaging. ACE-EPTI employs a newly designed variable density spatiotemporal encoding with self-navigation capability, that allows submillimeter in-plane resolution using only 3-shot. Moreover, an echo-train-shifted acquisition is developed to achieve minimal TE, together with an SNR-optimal readout length, leading to ~30% improvement in SNR efficiency over single-shot EPI. To recover the highly accelerated data with high image quality, a tailored subspace image reconstruction framework is developed, that corrects for odd/even-echo phase difference, shot-to-shot phase variation, and the B0 field changes due to field drift and eddy currents across different dynamics. After the phase-corrected subspace reconstruction, artifacts-free high-SNR diffusion images at multiple TEs are obtained with varying T2* weighting. ResultsSimulation, phantom and in-vivo experiments were performed, which validated the 3-shot spatiotemporal encoding provides accurate reconstruction at submillimeter resolution. The use of echo-train shifting and optimized readout length improves the SNR-efficiency by 27-36% over single-shot EPI. The reconstructed multi-TE diffusion images were demonstrated to be free from distortion (susceptibility and eddy currents) and phase/field variation induced artifacts. These improvements of ACE-EPTI enable improved diffusion tensor imaging and rich multi-TE information for diffusion-relaxometry analysis. ConclusionACE-EPTI was demonstrated to be an efficient and powerful technique for high-resolution diffusion imaging and diffusion-relaxometry, which provides high SNR, distortion- and blurring-free, and time-resolved multi-echo images by a fast 3-shot acquisition.

bioengineering↗

bioRxiv2021

Simultaneous pure T2 and varying T2'-weighted BOLD fMRI using Echo Planar Time-resolved Imaging (EPTI) for mapping laminar fMRI responses

Spin-echo (SE) BOLD fMRI has high microvascular specificity, and thus provides a more reliable means to localize neural activity compared to conventional gradient-echo BOLD fMRI. However, the most common SE BOLD acquisition method, SE-EPI, is known to suffer from T2' contrast contamination with undesirable draining vein bias. To address this, in this study, we extended a recently developed distortion/blurring-free multi-shot EPI technique, Echo-Planar Time-resolved Imaging (EPTI), to cortical-depth dependent SE-fMRI at 7T to test whether it could provide purer SE BOLD contrast with minimal T2' contamination for improved neuronal specificity. From the same acquisition, the time-resolved feature of EPTI also provides a series of asymmetric SE (ASE) images with varying T2' weightings, and enables extraction of data equivalent to conventional SE EPI with different echo train lengths (ETLs). This allows us to systematically examine how T2'-contribution affects different SE acquisition strategies using a single dataset. A low-rank spatiotemporal subspace reconstruction was implemented for the SE-EPTI acquisition, which incorporates corrections for both shot-to-shot phase variations and dynamic B0 drifts. SE-EPTI was used in a visual task fMRI experiment to demonstrate that i) the pure SE image provided by EPTI results in the highest microvascular specificity; ii) the ASE EPTI series, with a graded introduction of T2' weightings at time points farther away from the pure SE, show a gradual sensitivity increase along with increasing draining vein bias; iii) the longer ETL seen in conventional SE EPI acquisitions will induce more draining vein bias. Consistent results were observed across multiple subjects, demonstrating the robustness of the proposed technique for SE-BOLD fMRI with high specificity.

neuroscience↗

bioRxiv2021

Ultrafast high-resolution multi-parametric brain MRI using 3D Echo Planar Time-resolved Imaging

Multi-parametric quantitative MRI has shown great potential to improve the sensitivity and specificity of clinical diagnosis and to enhance our understanding of complex brain processes, but suffers from long scan time especially at high spatial resolution. To address this long-standing challenge, we introduce a novel approach, termed 3D Echo Planar Time-resolved Imaging (3D-EPTI), which significantly increases the acceleration capacity of MRI sampling, and provides high acquisition efficiency for multi-parametric MRI. This is achieved by exploiting the spatiotemporal correlation of MRI data at multiple timescales through new encoding strategies within and between efficient continuous readouts. Specifically, an optimized spatiotemporal CAIPI encoding within the readouts combined with a radial-block sampling strategy across the readouts enables an acceleration rate of 800 folds in the k-t space. A subspace reconstruction was employed to resolve thousands of artifact-free high-quality multi-contrast images spaced at a time interval of ~1 ms. We have demonstrated the ability of 3D-EPTI to provide robust and repeatable whole-brain simultaneous T1, T2, T2*, PD and B1+ mapping at high isotropic resolution within minutes (e.g., 1-mm isotropic resolution in 3 minutes), and to enable submillimeter multi-parametric imaging to study detailed brain structures. HighlightsO_LIUltra-fast acquisition for 3D multi-parametric quantitative MRI. C_LIO_LISimultaneous T1 T2 T2* PD and B1+ mapping. C_LIO_LI3-minute scan at 1-mm isotropic resolution with whole-brain coverage. C_LIO_LIMulti-parametric mapping at 700-m isotropic resolution in 10 minutes. C_LIO_LIRepeatable quantification and cortical-depth analysis. C_LI

bioengineering↗

bioRxiv2021

A 48-Channel Receive Array Coil for Mesoscopic Diffusion-Weighted MRI of Human ex vivo Brain Imaging on the 3T Connectome Scanner

In vivo diffusion-weighted magnetic resonance imaging is limited in signal-to-noise-ratio (SNR) and acquisition time, which constrains spatial resolution to the macroscale regime. Ex vivo imaging, which allows for arbitrarily long scan times, is critical for exploring human brain structure in the mesoscale regime without loss of SNR. Standard head array coils designed for patients are sub-optimal for imaging ex vivo whole brain specimens. The goal of this work was to design and construct a 48-channel ex vivo whole brain array coil for high-resolution and high b-value diffusion-weighted imaging on a 3T Connectome scanner. The coil was validated with bench measurements and characterized by imaging metrics on an agar brain phantom and an ex vivo human brain sample. The two-segment coil former was constructed for a close fit to a whole human brain, with small receive elements distributed over the entire brain. Imaging tests including SNR and G-factor maps were compared to a 64-channel head coil designed for in vivo use. There was a 2.9-fold increase in SNR in the peripheral cortex and a 1.3-fold gain in the center when compared to the 64-ch head coil. The 48-channel ex vivo whole brain coil also decreases noise amplification in highly parallel imaging, allowing acceleration factors of approximately one unit higher for a given noise amplification level. The acquired diffusion-weighted images in a whole ex vivo brain specimen demonstrate the applicability of the developed coil for high-resolution and high b-value diffusion-weighted ex vivo brain MRI studies.

bioengineering↗

bioRxiv2020

In vivo human whole-brain Connectom diffusion MRI dataset at 760 μm isotropic resolution

We present a whole-brain in vivo diffusion MRI (dMRI) dataset acquired at 760 m isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy subject. The creation of this benchmark dataset is possible through the synergistic use of advanced acquisition hardware and software including the high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition method, and parallel imaging reconstruction with advanced ghost reduction algorithm. With its unprecedented resolution, SNR and image quality, we envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance the understanding of human brain structures and connectivity. This comprehensive dataset can also be used as a test bed for new modeling, sub-sampling strategies, denoising and processing algorithms, potentially providing a common testing platform for further development of in vivo high resolution dMRI techniques. Whole brain anatomical T1-weighted and T2-weighted images at submillimeter scale along with field maps are also made available.

neuroscience↗

bioRxiv2019

7 Tesla MRI of the ex vivo human brain at 100 micron resolution

We present an ultra-high resolution MRI dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 m isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of scan time (25 hours per flip angle), allowing derivation of a T1 parameter map and synthesized FLASH volumes. This dataset provides an unprecedented view of the three-dimensional neuroanatomy of the human brain. To optimize the utility of this resource, we warped the dataset into standard stereotactic space. We now distribute the dataset in both native space and stereotactic space to the academic community via multiple platforms. We envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance understanding of human brain anatomy in health and disease.\n\n\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@17d0265org.highwire.dtl.DTLVardef@285366org.highwire.dtl.DTLVardef@17b53c6org.highwire.dtl.DTLVardef@1b90277org.highwire.dtl.DTLVardef@150ea14_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗