JCBFM, 2025
Torben D Pearson, Sarah Bricault, Chi-Hyeon Yoo, Hsiao-Ying Wey
Preclinical PET studies offer the opportunity to elucidate molecular mechanisms underlying early neurodevelopment with minimal invasiveness. We demonstrated the feasibility of fetal brain PET in four pregnant rats (n = 42 fetuses). [18F]FDG uptake in rat fetuses was readily visualized by PET imaging. Additionally, in vivo fetal brain [18F]FDG concentration (standardized uptake value (SUV)) was significantly correlated with ex vivo SUV from matched post-mortem brains (R2 = 0.90, p < 0.001). We further investigated the effect of the dopamine receptor antagonist haloperidol on cerebral glucose metabolism (CMRglu) and [11C]raclopride binding in maternal and fetal brains. Dopamine D2 receptor blockade by haloperidol resulted in significant decreases (p < 0.001, n = 33 vs 9 fetuses) in in vivo CMRglu and ex vivo [18F]FDG SUV. Consistently, haloperidol pretreatment significantly decreased [11C]raclopride SUV ratio (SUVR) by 17% (p < 0.001, n = 6 vs 6 fetuses) in the fetal whole-brain, using the maternal cerebellum as the reference region. In all, our results show that PET/CT imaging of the fetal rat brain can reliably quantify specific molecular targets in vivo, and future translational studies of neurodevelopment are feasible in this model.
Preclinical PET imaging of the developing fetus during pregnancy: Current state and future potential
JCBFM, 2025
Torben D Pearson*, Sarah Bricault*, Yu-Shiuan Lin, Katelyn E Barusso, Samhitha Bodangi, Hsiao-Ying Wey
During pregnancy, the fetus is subject to complex interactions of biological and environmental factors that can influence developmental trajectories even into adulthood. Although several factors, such as maternal malnutrition and substance abuse, have been associated with offspring development, the mechanisms through which short- and long-term effects manifest in the fetus are not well understood. To this end, positron emission tomography (PET) imaging using preclinical models has been a promising and underutilized technique for investigating fetal exposure and physiology in utero with minimal invasiveness. Herein, we review the application of PET imaging to fetal medicine and survey the limitations and opportunities for future longitudinal studies of development. Over the past two decades, several studies have utilized preclinical PET in quantitative studies of maternal-fetal exchange dynamics of pharmaceuticals, environmental toxins, or drugs of abuse. Another application has shown [18F]FDG PET to be a potential biomarker for fetal glucose transport, hypoxia, and brain function in utero. In contrast, only a few studies have employed reversibly binding radioligands to quantify protein markers of dopaminergic signaling and synaptic density in the fetal brain. As PET technology continues to improve, our review highlights a future role for PET in longitudinal studies of fetal health and development.
Nature Communications, 2024
Sarah Bricault, Miranda Dawson, Jiyoung Lee, Mitul Desai, Miriam Schwalm, Kevin Sunho Chung, Elizabeth DeTienne, Erinn Fagan, Nan Li, Andrew Becker, Sureshkumar Muthupalani, Jan-Philipp Fränken, Dimitris A. Pinotsis & Alan Jasanoff
The correlational structure of brain activity dynamics in the absence of stimuli or behavior is often taken to reveal intrinsic properties of neural function. To test the limits of this assumption, we analyzed peripheral contributions to resting state activity measured by fMRI in unanesthetized, chemically immobilized male rats that emulate human neuroimaging conditions. We find that perturbation of somatosensory input channels modifies correlation strengths that relate somatosensory areas both to one another and to higher-order brain regions, despite the absence of ostensible stimuli or movements. Resting state effects are mediated by the same peripheral and thalamic structures that relay responses to overt sensory stimuli. The impact of basal peripheral input is reduced in a rat model of autism, which displays both lower somatosensory functional connectivity and insensitivity to vibrissa inactivation. These results demonstrate the influence of extrinsic influences on resting state brain phenotypes in health and disease.
Proceedings of Bridges 2024: Mathematics, Art, Music, Architecture, Culture
Sarah Bricault
The Dragon Curve is a fractal that can be created by iteratively folding a single line according to a set algorithm. Every line segment is replaced in the subsequent iteration by two line segments that intersect at right angles with the end points unchanged. The following novel implementation results in a class of fractals referred to here as Folding Curves. One can fold the initial line according to a repeating pattern of fold commands, called here the fold command list. When one reaches the end of the fold command list, one returns to the beginning. For example, a fold command list of [0 1 1 0] produces an interesting semi-self-similar fractal. Additional complexity and beauty can be added by starting with a shape that is not a single line or implementing the fractals in a physical medium.
ACS Central Science, 2024
Michael S. Placzek, Daniel K. Wilton, Michel Weiwer, Mariah A. Manter, Sarah E. Reid, Christopher J. Meyer, Arthur J. Campbell, Besnik Bajrami, Antoine Bigot, Sarah Bricault, Agathe Fayet, Arnaud Frouin, Frederick Gergits, Mehak Gupta, Wei Jiang, Michelle Melanson, Chiara D. Romano, Misha M. Riley, Jessica M. Wang, Hsiao-Ying Wey, Florence F. Wagner, Beth Stevens, and Jacob M. Hooker
Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In the central nervous system (CNS), COX-2 is implicated in neurodegenerative and psychiatric disorders as a potential therapeutic target and biomarker. However, clinical studies with COX-2 have yielded inconsistent results, partly due to limited mechanistic understanding of how COX-2 activity relates to CNS pathology. Therefore, developing COX-2 positron emission tomography (PET) radiotracers for human neuroimaging is of interest. This study introduces [11C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer. [11C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, and free fraction in the brain. Evaluated through in vivo PET neuroimaging in rodent models with human COX-2 overexpression, [11C]BRD1158 demonstrated high brain uptake, fast target-engagement, functional reversibility, and excellent specific binding, which is advantageous for human imaging applications. Lastly, post-mortem samples from Huntington’s disease (HD) patients and preclinical HD mouse models showed that COX-2 levels were elevated specifically in disease-affected brain regions, primarily from increased expression in microglia. These findings indicate that COX-2 holds promise as a novel clinical marker of HD onset and progression, one of many potential applications of [11C]BRD1158 human PET.
Nature Communications, 2020
Sarah Bricault, Ali Barandov, Peter Harvey, Elizabeth DeTienne, Aviad Hai & Alan Jasanoff
Targeted manipulations of neural activity are essential approaches in neuroscience and neurology, but monitoring such procedures in the living brain remains a significant challenge. Here we introduce a paramagnetic analog of the drug muscimol that enables targeted neural inactivation to be performed with feedback from magnetic resonance imaging. We validate pharmacological properties of the compound in vitro, and show that its distribution in vivo reliably predicts perturbations to brain activity.
Nature Communications, 2018
Felix Sigmund, Christoph Massner, Philipp Erdmann, Anja Stelzl, Hannes Rolbieski, Mitul Desai, Sarah Bricault, Tobias P. Wörner, Joost Snijder, Arie Geerlof, Helmut Fuchs, Martin Hrabĕ de Angelis, Albert J. R. Heck, Alan Jasanoff, Vasilis Ntziachristos, Jürgen Plitzko & Gil G. Westmeyer
We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB,C) results in efficient iron sequestration producing substantial contrast by magnetic resonance imaging (MRI) and allowing for magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells are also excellent genetically encoded reporters for electron microscopy (EM). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.
NeuroImage, 2017
Ana M.Fiallos, Sarah J.Bricault, Lili X.Cai, Hermoon A.Worku, Matthew T.Colonnese, Gil G.Westmeyer, AlanJasanoff
Evaluation of the magnitudes of intrinsically rewarding stimuli is essential for assigning value and guiding behavior. By combining parametric manipulation of a primary reward, medial forebrain bundle (MFB) microstimulation, with functional magnetic imaging (fMRI) in rodents, we delineated a broad network of structures activated by behaviorally characterized levels of rewarding stimulation. Correlation of psychometric behavioral measurements with fMRI response magnitudes revealed regions whose activity corresponded closely to the subjective magnitude of rewards. The largest and most reliable focus of reward magnitude tracking was observed in the shell region of the nucleus accumbens (NAc). Although the nonlinear nature of neurovascular coupling complicates interpretation of fMRI findings in precise neurophysiological terms, reward magnitude tracking was not observed in vascular compartments and could not be explained by saturation of region-specific hemodynamic responses. In addition, local pharmacological inactivation of NAc changed the profile of animals’ responses to rewards of different magnitudes without altering mean reward response rates, further supporting a hypothesis that neural population activity in this region contributes to assessment of reward magnitudes.
Journal of Neurophysiology, 2013
Judith McLean, Sarah Bricault, and Marc F. Schmidt
Much is known about the neuronal cell types and circuitry of the mammalian respiratory brainstem and its role in normal, quiet breathing. Our understanding of the role of respiration in the context of vocal production, however, is very limited. Songbirds contain a well-defined neural circuit, known as the song system, which is necessary for song production and is strongly coupled to the respiratory system. A major target of this system is nucleus parambigualis (PAm) in the ventrolateral medulla, a structure that controls inspiration by way of its bulbospinal projections but is also an integral part of the song-pattern generation circuit by way of its “thalamocortical” projections to song-control nuclei in the telencephalon. We have mapped out PAm to characterize the cell types and its functional organization. Extracellular single units were obtained in anesthetized adult male zebra finches while measuring air sac pressure to monitor respiration. Single units were characterized by their discharge patterns and the phase of the activity in the respiratory cycle. Several classes of neurons were identified and were analogous to those reported for mammalian medullary respiratory neurons. The majority of the neurons in PAm was classified as inspiratory augmenting or preinspiratory, although other basic discharge patterns were observed as well. The well-characterized connectivity of PAm within the vocal motor circuit and the similarity of its neural firing patterns to the rostral ventral respiratory group and pre-Bötzinger complex of mammals make it an ideal system for investigating the integration of breathing and vocalization.