[ { "id": "authors:drbq7-emv23", "collection": "authors", "collection_id": "drbq7-emv23", "cite_using_url": "https://authors.library.caltech.edu/records/drbq7-emv23", "type": "monograph", "title": "VARS-fUSI: Variable Sampling for Fast and Efficient Functional Ultrasound Imaging using Neural Operators", "author": [ { "family_name": "Tolooshams", "given_name": "Bahareh", "orcid": "0000-0002-5955-6535", "clpid": "Tolooshams-Bahareh" }, { "family_name": "Lin", "given_name": "Lydia", "orcid": "0009-0002-8394-7621", "clpid": "Lin-Lydia" }, { "family_name": "Callier", "given_name": "Thierri", "orcid": "0000-0001-8645-2005", "clpid": "Callier-Thierri" }, { "family_name": "Wang", "given_name": "Jiayun", "orcid": "0000-0002-8356-2775", "clpid": "Wang-Jiayun" }, { "family_name": "Pal", "given_name": "Sanvi", "orcid": "0009-0007-0530-642X", "clpid": "Pal-Sanvi" }, { "family_name": "Chandrashekar", "given_name": "Aditi", "orcid": "0009-0003-3244-9048", "clpid": "Chandrashekar-Aditi-J" }, { "family_name": "Rabut", "given_name": "Claire", "orcid": "0000-0002-4571-1215", "clpid": "Rabut-Claire-M" }, { "family_name": "Li", "given_name": "Zongyi", "orcid": "0000-0003-2081-9665", "clpid": "Li-Zongyi" }, { "family_name": "Blagden", "given_name": "Chase", "orcid": "0009-0002-3077-2223", "clpid": "Blagden-Chase" }, { "family_name": "Norman", "given_name": "Sumner L.", "orcid": "0000-0001-9945-697X", "clpid": "Norman-Sumner-L" }, { "family_name": "Azizzadenesheli", "given_name": "Kamyar", "orcid": "0000-0001-8507-1868" }, { "family_name": "Liu", "given_name": "Charles", "orcid": "0000-0001-6423-8577", "clpid": "Liu-Charles-Y" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Andersen", "given_name": "Richard A.", "orcid": "0000-0002-7947-0472", "clpid": "Andersen-R-A" }, { "family_name": "Anandkumar", "given_name": "Anima", "orcid": "0000-0002-6974-6797", "clpid": "Anandkumar-A" } ], "abstract": "

Functional ultrasound imaging (fUSI) is a promising neuroimaging method that infers neural activity by detecting cerebral blood volume changes. It offers high sensitivity and spatial resolution relative to fMRI and is an epidural alternative to electrophysiology for medical and neuroscience applications, including brain-computer interfaces. However, current fUSI methods require hundreds of compounded images and ultrasound pulse emissions, leading to high computational costs, memory demands, and potential probe heating. We propose VARiable Sampling fUSI (VARS-fUSI), the first deep learning fUSI method to allow for different sampling durations and rates during training and inference by using neural operators. VARS-fUSI reconstructs high-quality fUSI images using 10 − 15% of the time or sampling rate needed per image while preserving decodable behavior-correlated signals. Additionally, VARS-fUSI offers efficient finetuning for generalization to new animals and humans. Demonstrated across mouse, monkey, and human data, VARS-fUSI achieves state-of-the-art performance, enhancing imaging efficiency by significantly reducing storage and processing needs.

", "doi": "10.1101/2025.04.16.649237", "publisher": "arXiv", "publication_date": "2025-04-23" }, { "id": "authors:qnxrm-ncs15", "collection": "authors", "collection_id": "qnxrm-ncs15", "cite_using_url": "https://authors.library.caltech.edu/records/qnxrm-ncs15", "type": "monograph", "title": "Ultrasonic reporters of calcium for deep tissue imaging of cellular signals", "author": [ { "family_name": "Jin", "given_name": "Zhiyang", "orcid": "0000-0002-4411-6991", "clpid": "Jin-Zhiyang" }, { "family_name": "Lakshmanan", "given_name": "Anupama", "orcid": "0000-0002-6702-837X", "clpid": "Lakshmanan-Anupama" }, { "family_name": "Zhang", "given_name": "Ruby", "orcid": "0009-0001-4410-945X", "clpid": "Zhang-Ruby" }, { "family_name": "Tran", "given_name": "Teresa A.", "clpid": "Tran-Teresa-A" }, { "family_name": "Rabut", "given_name": "Claire", "orcid": "0000-0002-4571-1215", "clpid": "Rabut-Claire" }, { "family_name": "Dutka", "given_name": "Przemys\u0142aw", "orcid": "0000-0003-3819-1618", "clpid": "Dutka-Przemys\u0142aw" }, { "family_name": "Duan", "given_name": "Mengtong", "orcid": "0000-0002-1601-8876", "clpid": "Duan-Mengtong" }, { "family_name": "Hurt", "given_name": "Robert C.", "orcid": "0000-0002-4347-6901", "clpid": "Hurt-Robert-C" }, { "family_name": "Malounda", "given_name": "Dina", "orcid": "0000-0001-7086-9877", "clpid": "Malounda-Dina" }, { "family_name": "Yao", "given_name": "Yuxing", "orcid": "0000-0003-0337-6372", "clpid": "Yao-Yuxing" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "abstract": "
\n

Calcium imaging has enabled major biological discoveries. However, the scattering of light by tissue limits the use of standard fluorescent calcium indicators in living animals. To address this limitation, we introduce the first genetically encoded ultrasonic reporter of calcium (URoC). Based on a unique class of air-filled protein nanostructures called gas vesicles, we engineered URoC to produce elevated nonlinear ultrasound signal upon binding to calcium ions. With URoC expressed in mammalian cells, we demonstrate noninvasive ultrasound imaging of calcium signaling in vivo during drug-induced receptor activation. URoC brings the depth and resolution advantages of ultrasound to the in vivo imaging of dynamic cellular function and paves the way for acoustic biosensing of a broader variety of biological signals.

\n
", "doi": "10.1101/2023.11.09.566364", "pmcid": "PMC10659314", "publication_date": "2023-11-12" }, { "id": "authors:gsq04-jx080", "collection": "authors", "collection_id": "gsq04-jx080", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-181929000.6", "type": "monograph", "title": "Self-regulating living material with temperature-dependent light absorption", "author": [ { "family_name": "Xiong", "given_name": "Lealia L.", "orcid": "0000-0001-7636-5936", "clpid": "Xiong-Lealia-L" }, { "family_name": "Garrett", "given_name": "Michael A.", "clpid": "Garrett-Michael-A" }, { "family_name": "Kornfield", "given_name": "Julia A.", "orcid": "0000-0001-6746-8634", "clpid": "Kornfield-J-A" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "abstract": "Engineered living materials (ELMs) exhibit desirable characteristics of the living component, including growth and repair, and responsiveness to external stimuli. Escherichia coli are a promising constituent of ELMs because they are very tractable to genetic engineering, produce heterologous proteins readily, and grow exponentially. However, seasonal variation in ambient temperature presents a challenge in deploying ELMs outside of a laboratory environment, because E. coli growth rate is impaired both below and above 37\u00b0C. Here, we develop a genetically-encoded mechanism for autonomous temperature homeostasis in ELMs containing E. coli by engineering circuits that control the expression of a light-absorptive chromophore in response to changes in temperature. We demonstrate that below 36\u00b0C, our engineered E. coli increase in pigmentation, causing an increase in sample temperature and growth rate above non-pigmented counterparts in a model planar ELM. On the other hand, above 36\u00b0C, they decrease in pigmentation, protecting their growth compared to bacteria with temperature-independent high pigmentation. Integrating our temperature homeostasis circuit into an ELM has the potential to improve living material performance by optimizing growth and protein production in the face of seasonal temperature changes.", "doi": "10.1101/2023.03.11.532239", "publication_date": "2023-03-13" }, { "id": "authors:9xjx3-smy39", "collection": "authors", "collection_id": "9xjx3-smy39", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182888000.72", "type": "monograph", "title": "Decoding Motor Plans Using a Closed-Loop Ultrasonic Brain-Machine Interface", "author": [ { "family_name": "Griggs", "given_name": "Whitney S.", "orcid": "0000-0003-2941-6803", "clpid": "Griggs-Whitney-S" }, { "family_name": "Norman", "given_name": "Sumner L.", "orcid": "0000-0001-9945-697X", "clpid": "Norman-Sumner-Lee" }, { "family_name": "Deffieux", "given_name": "Thomas", "orcid": "0000-0001-9114-2028", "clpid": "Deffieux-Thomas" }, { "family_name": "Segura", "given_name": "Florian", "clpid": "Segura-Florian" }, { "family_name": "Osmanski", "given_name": "Bruno-F\u00e9lix", "orcid": "0000-0003-1198-5303", "clpid": "Osmanski-Bruno-F\u00e9lix" }, { "family_name": "Chau", "given_name": "Geeling", "orcid": "0000-0002-7634-8586", "clpid": "Chau-Geeling" }, { "family_name": "Christopoulos", "given_name": "Vasileios", "orcid": "0000-0002-0541-8700", "clpid": "Christopoulos-Vasileios-N" }, { "family_name": "Liu", "given_name": "Charles", "orcid": "0000-0001-6423-8577", "clpid": "Liu-Charles-Y" }, { "family_name": "Tanter", "given_name": "Micka\u00ebl", "orcid": "0000-0001-7739-8051", "clpid": "Tanter-Micka\u00ebl" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Andersen", "given_name": "Richard A.", "orcid": "0000-0002-7947-0472", "clpid": "Andersen-R-A" } ], "abstract": "Brain-machine interfaces (BMIs) can be transformative for people living with chronic paralysis. BMIs translate brain signals into computer commands, bypassing neurological impairments and enabling people with neurological injury or disease to control computers, robots, and more with nothing but thought. State-of-the-art BMIs have already made this future a reality in limited clinical trials. However, high performance BMIs currently require highly invasive electrodes in the brain. Device degradation limits longevity to about 5 years. Their field of view is small, restricting the number, and type, of applications possible. The next generation of BMI technology should include being longer lasting, less invasive, and scalable to sense activity from large regions of the brain. Functional ultrasound neuroimaging is a recently developed technique that meets these criteria. In this present study, we demonstrate the first online, closed-loop ultrasonic brain-machine interface. We used 2 Hz real-time functional ultrasound to measure the neurovascular activity of the posterior parietal cortex in two nonhuman primates (NHPs) as they performed memory-guided movements. We streamed neural signals into a classifier to predict the intended movement direction. These predictions controlled a behavioral task in real-time while the NHP did not produce overt movements. Both NHPs quickly succeeded in controlling up to eight independent directions using the BMI. Furthermore, we present a simple method to \"pretrain\" the BMI using data from previous sessions. This enables the BMI to work immediately from the start of a session without acquiring extensive additional training data. This work establishes, for the first time, the feasibility of an ultrasonic BMI and prepares for future work on a next generation of minimally invasive BMIs that can restore function to patients with neurological, physical, or even psychiatric impairments.", "doi": "10.1101/2022.11.10.515371", "publication_date": "2022-11-14" }, { "id": "authors:se8kp-9jq86", "collection": "authors", "collection_id": "se8kp-9jq86", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220706-965638000", "type": "monograph", "title": "Geometric effects in gas vesicle buckling under ultrasound", "author": [ { "family_name": "Salahshoor", "given_name": "Hossein", "orcid": "0000-0002-7264-7650", "clpid": "Salahshoor-Hossein" }, { "family_name": "Yao", "given_name": "Yuxing", "orcid": "0000-0003-0337-6372", "clpid": "Yao-Yuxing" }, { "family_name": "Dutka", "given_name": "Przemys\u0142aw", "orcid": "0000-0003-3819-1618", "clpid": "Dutka-Przemys\u0142aw" }, { "family_name": "Nystr\u00f6m", "given_name": "Nivin N.", "orcid": "0000-0001-6288-6060", "clpid": "Nystr\u00f6m-Nivin-N" }, { "family_name": "Jin", "given_name": "Zhiyang", "orcid": "0000-0002-4411-6991", "clpid": "Jin-Zhiyang" }, { "family_name": "Min", "given_name": "Ellen", "clpid": "Min-Ellen" }, { "family_name": "Malounda", "given_name": "Dina", "orcid": "0000-0001-7086-9877", "clpid": "Malounda-Dina" }, { "family_name": "Jensen", "given_name": "Grant J.", "orcid": "0000-0003-1556-4864", "clpid": "Jensen-G-J" }, { "family_name": "Ortiz", "given_name": "Michael", "orcid": "0000-0001-5877-4824", "clpid": "Ortiz-M" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "abstract": "Acoustic reporter genes based on gas vesicles (GVs) have enabled the use of ultrasound to noninvasively visualize cellular function in vivo. The specific detection of GV signals relative to background acoustic scattering in tissues is facilitated by nonlinear ultrasound imaging techniques taking advantage of the sonomechanical buckling of GVs. However, the effect of geometry on the buckling behavior of GVs under exposure to ultrasound has not been studied. To understand such geometric effects, we developed computational models of GVs of various lengths and diameters and used finite element simulations to predict their threshold buckling pressures and post-buckling deformations. We demonstrated that the GV diameter has an inverse cubic relation to the threshold buckling pressure, whereas length has no substantial effect. To complement these simulations, we experimentally probed the effect of geometry on the mechanical properties of GVs and the corresponding nonlinear ultrasound signals. The results of these experiments corroborate our computational predictions. This study provides fundamental insights into how geometry affects the sonomechanical properties of GVs, which, in turn, can inform further engineering of these nanostructures for high-contrast, nonlinear ultrasound imaging.STATEMENT OF SIGNIFICANCEGas vesicles (GVs) are an emerging class of genetically encodable and engineerable imaging agents for ultrasound whose sonomechanical buckling generates nonlinear contrast to enable sensitive and specific imaging in highly scattering biological systems. Though the effect of protein composition on GV buckling has been studied, the effect of geometry has not previously been addressed. This study reveals that geometry, especially GV diameter, significantly alters the threshold acoustic pressures required to induce GV buckling. Our computational predictions and experimental results provide fundamental understanding of the relationship between GV geometry and buckling properties and underscore the utility of GVs for nonlinear ultrasound imaging. Additionally, our results provide suggestions to further engineer GVs to enable in vivo ultrasound imaging with greater sensitivity and higher contrast.", "doi": "10.1101/2022.06.27.497663", "publication_date": "2022-06-29" }, { "id": "authors:yvx4e-r7d09", "collection": "authors", "collection_id": "yvx4e-r7d09", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220706-965078000", "type": "monograph", "title": "Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET", "author": [ { "family_name": "Dutka", "given_name": "Przemys\u0142aw", "orcid": "0000-0003-3819-1618", "clpid": "Dutka-Przemys\u0142aw" }, { "family_name": "Metskas", "given_name": "Lauren Ann", "orcid": "0000-0002-8073-6960", "clpid": "Metskas-Lauren-Ann" }, { "family_name": "Hurt", "given_name": "Robert C.", "orcid": "0000-0002-4347-6901", "clpid": "Hurt-Robert-C" }, { "family_name": "Salahshoor", "given_name": "Hossein", "orcid": "0000-0002-7264-7650", "clpid": "Salahshoor-Hossein" }, { "family_name": "Wang", "given_name": "Ting-Yu", "clpid": "Wang-Ting-Yu" }, { "family_name": "Malounda", "given_name": "Dina", "orcid": "0000-0001-7086-9877", "clpid": "Malounda-Dina" }, { "family_name": "Lu", "given_name": "George", "orcid": "0000-0002-4689-9686", "clpid": "Lu-George-Jiaozhi" }, { "family_name": "Chou", "given_name": "Tsui-Fen", "orcid": "0000-0003-2410-2186", "clpid": "Chou-Tsui-Fen" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Jensen", "given_name": "Grant J.", "orcid": "0000-0003-1556-4864", "clpid": "Jensen-G-J" } ], "abstract": "Gas vesicles (GVs) are gas-filled protein nanostructures employed by several species of bacteria and archaea as flotation devices to enable access to optimal light and nutrients. The unique physical properties of GVs have led to their use as genetically-encodable contrast agents for ultrasound and MRI. Currently, however, the structure and assembly mechanism of GVs remain unknown. Here we employ cryo-electron tomography to reveal how the GV shell is formed by a helical filament of highly conserved GvpA subunits. This filament changes polarity at the center of the GV cylinder\u2014a site that may act as an elongation center. High-resolution subtomogram averaging reveals a corrugated pattern of the shell arising from polymerization of GvpA into a \u03b2-sheet. The accessory protein GvpC forms a helical cage around the GvpA shell, providing structural reinforcement. Together, our results help explain the remarkable mechanical properties of GVs and their ability to adopt different diameters and shapes.", "doi": "10.1101/2022.06.21.496981", "publication_date": "2022-06-22" }, { "id": "authors:xtznt-jpb64", "collection": "authors", "collection_id": "xtznt-jpb64", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220601-257870000", "type": "monograph", "title": "Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo", "author": [ { "family_name": "Kim", "given_name": "Whee-Soo", "clpid": "Kim-Whee-Soo" }, { "family_name": "Min", "given_name": "Sungjin", "clpid": "Min-Sungjin" }, { "family_name": "Kim", "given_name": "Su Kyeom", "clpid": "Kim-Su-Kyeom" }, { "family_name": "Kang", "given_name": "Sunghwi", "clpid": "Kang-Sunghwi" }, { "family_name": "Davis", "given_name": "Hunter", "orcid": "0000-0003-1655-692X", "clpid": "Davis-Hunter-C" }, { "family_name": "Bar-Zion", "given_name": "Avinoam", "orcid": "0000-0002-7564-9467", "clpid": "Bar-Zion-Avinoam" }, { "family_name": "Malounda", "given_name": "Dina", "orcid": "0000-0001-7086-9877", "clpid": "Malounda-Dina" }, { "family_name": "Kim", "given_name": "Yu Heun", "clpid": "Kim-Yu-Heun" }, { "family_name": "An", "given_name": "Soohwan", "orcid": "0000-0002-8837-1898", "clpid": "An-Soohwan" }, { "family_name": "Lee", "given_name": "Jae-Hyun", "orcid": "0000-0002-0760-0071", "clpid": "Lee-Jae-Hyun" }, { "family_name": "Bae", "given_name": "Soo Han", "orcid": "0000-0002-8007-2906", "clpid": "Bae-Soo-Han" }, { "family_name": "Lee", "given_name": "Jin Gu", "clpid": "Lee-Jin-Gu" }, { "family_name": "Kwak", "given_name": "Minsuk", "clpid": "Kwak-Minsuk" }, { "family_name": "Cho", "given_name": "Seung-Woo", "clpid": "Cho-Seung-Woo" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Cheon", "given_name": "Jinwoo", "orcid": "0000-0001-8948-5929", "clpid": "Cheon-Jinwoo" } ], "abstract": "Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes, and is a major goal in the field of mechanobiology. However, existing biosensors for 3D tissue mechanics, primarily based on fluorescent emissions and deformable materials, are limited for in vivo measurement due to the limited light penetration and poor material stability inside intact, living organisms. While magneto-motive ultrasound (MMUS), which uses superparamagnetic nanoparticles as imaging contrast agents, has emerged as a promising modality for real-time in vivo imaging of tissue mechanics, it has poor sensitivity and spatiotemporal resolution. To overcome these limitations, we introduce magneto-gas vesicles (MGVs), a unique class of protein nanostructures based on gas vesicles and magnetic nanoparticles that produces differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid protein nanostructures significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term, and quantitative measurement of mechanical properties within 3D tissues and organs in vivo. We demonstrated the performance of MGV-based mechano-sensors in vitro, in fibrosis models of organoids, and in vivo in mouse liver fibrosis models.", "doi": "10.1101/2022.05.26.493158", "publication_date": "2022-05-28" }, { "id": "authors:b187k-52y24", "collection": "authors", "collection_id": "b187k-52y24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220128-118576700", "type": "monograph", "title": "Smart sealants for prevention and monitoring of gastrointestinal anastomotic leaks using portable smartphone-controlled ultrasound transducers", "author": [ { "family_name": "Anthis", "given_name": "Alexandre H. C.", "clpid": "Anthis-Alexandre-H-C" }, { "family_name": "Abundo", "given_name": "Maria Paulene", "clpid": "Abundo-Maria-Paulene" }, { "family_name": "Neuer", "given_name": "Anna L.", "clpid": "Neuer-Anna-Lena" }, { "family_name": "Tsolaki", "given_name": "Elena", "orcid": "0000-0003-1436-7834", "clpid": "Tsolaki-Elena" }, { "family_name": "Rosendorf", "given_name": "Jachym", "clpid": "Rosendorf-Jachym" }, { "family_name": "Rduch", "given_name": "Thomas", "clpid": "Rduch-Thomas" }, { "family_name": "Starsich", "given_name": "Fabian H. L.", "clpid": "Starsich-Fabian-H-L" }, { "family_name": "Liska", "given_name": "Vaclav", "orcid": "0000-0002-7755-3856", "clpid": "Liska-Vaclav" }, { "family_name": "Schlegel", "given_name": "Andrea A.", "orcid": "0000-0002-9385-9847", "clpid": "Schlegel-Andrea-A" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Herrmann", "given_name": "Inge K.", "orcid": "0000-0002-3018-6796", "clpid": "Herrmann-Inge-K" } ], "abstract": "Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of the cases. Penetration of digestive fluids into the peritoneal cavity may lead to dreadful complications, including sepsis and premature death. Modern suture supports and tissue adhesives only insufficiently address the issue. Due to the scarcity of alternatives, surgeons rely on monitoring surrogate markers and clinical symptoms, which oftentimes lack sensitivity and specificity, hence only offering late-stage detection of already fully developed leaks. \nHere, a first-of-its-kind, modular, intelligent suture support patch capable of sealing and monitoring leaks under harsh gastrointestinal conditions is presented. The smart adhesive layered hydrogel patch provides, in addition to unprecedented tissue sealing under most demanding conditions, unique leak-detection capabilities based on pH and/or enzyme-responsive sensing elements, which can be read out by non-invasive point-of-need ultrasound imaging. Reliable detection of the breaching of sutures in as little as 3 hours in intestinal leak and 15 minutes in gastric leak conditions, and before an actual leak develops, is demonstrated. This technology paves the way for next-generation suture support materials that offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.", "doi": "10.1101/2022.01.24.477460", "publication_date": "2022-01-27" }, { "id": "authors:gyqqx-fgf76", "collection": "authors", "collection_id": "gyqqx-fgf76", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211122-182853483", "type": "monograph", "title": "Doppler Slicing for Ultrasound Super-Resolution Without Contrast Agents", "author": [ { "family_name": "Bar-Zion", "given_name": "Avinoam", "orcid": "0000-0002-7564-9467", "clpid": "Bar-Zion-Avinoam" }, { "family_name": "Solomon", "given_name": "Oren", "orcid": "0000-0003-0240-0852", "clpid": "Solomon-Oren" }, { "family_name": "Rabut", "given_name": "Claire", "orcid": "0000-0002-4571-1215", "clpid": "Rabut-Claire" }, { "family_name": "Maresca", "given_name": "David", "orcid": "0000-0002-4921-6406", "clpid": "Maresca-David" }, { "family_name": "Eldar", "given_name": "Yonina C.", "clpid": "Eldar-Yonina" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "abstract": "Much of the information needed for diagnosis and treatment monitoring of diseases like cancer and cardiovascular disease is found at scales below the resolution limit of classic ultrasound imaging. Recently introduced vascular super-localization methods provide more than a ten-fold improvement in spatial resolution by precisely estimating the positions of microbubble contrast agents. However, most vascular ultrasound scans are currently performed without contrast agents due to the associated cost, training, and post-scan monitoring. Here we show that super-resolution ultrasound imaging of dense vascular structures can be achieved using the natural contrast of flowing blood cells. Instead of relying on separable targets, we used Fourier-based decomposition to separate signals arising from the different scales of vascular structures while removing speckle noise using multi-ensemble processing. This approach enabled the use of compressed sensing for super-resolution imaging of the underlying vascular structures, improving resolution by a factor of four. Reconstruction of ultrafast mouse brain scans revealed details that could not be resolved in regular Doppler images, agreeing closely with bubble-based super-localization microscopy of the same fields of view. By combining multi-ensemble Doppler acquisitions with narrowband Fourier decomposition and computational super-resolution imaging, this approach opens new opportunities for affordable and scalable super-resolution ultrasound imaging.", "doi": "10.1101/2021.11.19.469083", "publication_date": "2021-11-21" }, { "id": "authors:qd2qe-p7926", "collection": "authors", "collection_id": "qd2qe-p7926", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210729-152223015", "type": "monograph", "title": "Engineering Viral Vectors for Acoustically Targeted Gene Delivery", "author": [ { "family_name": "Li", "given_name": "Hongyi", "orcid": "0000-0001-6970-0230", "clpid": "Li-Hongyi" }, { "family_name": "Heath", "given_name": "John E", "orcid": "0000-0002-5004-2693", "clpid": "Heath-John-E" }, { "family_name": "Trippett", "given_name": "James S.", "orcid": "0000-0003-4883-6547", "clpid": "Trippett-James-S" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" }, { "family_name": "Szablowski", "given_name": "Jerzy O.", "orcid": "0000-0001-7851-5408", "clpid": "Szablowski-Jerzy-O" } ], "abstract": "Targeted gene delivery to the brain is a critical tool for neuroscience research and has significant potential to treat human disease. However, the site-specific delivery of common gene vectors such as adeno-associated viruses (AAVs) is typically performed via invasive injections, limiting their scope of research and clinical applications. Alternatively, focused ultrasound blood-brain-barrier opening (FUS-BBBO), performed noninvasively, enables the site-specific entry of AAVs into the brain from systemic circulation. However, when used in conjunction with natural AAV serotypes, this approach has limited transduction efficiency, requires ultrasound parameters close to tissue damage limits, and results in undesirable transduction of peripheral organs. Here, we use high throughput in vivo selection to engineer new AAV vectors specifically designed for local neuronal transduction at the site of FUS-BBBO. The resulting vectors substantially enhance ultrasound-targeted gene delivery and neuronal tropism while reducing peripheral transduction, providing a more than ten-fold improvement in targeting specificity. In addition to enhancing the only known approach to noninvasively target gene delivery to specific brain regions, these results establish the ability of AAV vectors to be evolved for specific physical delivery mechanisms.", "doi": "10.1101/2021.07.26.453904", "publication_date": "2021-07-27" }, { "id": "authors:90sdk-fhv07", "collection": "authors", "collection_id": "90sdk-fhv07", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210429-092722876", "type": "monograph", "title": "Genomically Mined Acoustic Reporter Genes Enable In Vivo Monitoring of Tumors and Tumor-Homing Bacteria", "author": [ { "family_name": "Hurt", "given_name": "Robert C.", "orcid": "0000-0002-4347-6901", "clpid": "Hurt-Robert-C" }, { "family_name": "Buss", "given_name": "Marjorie T.", "orcid": "0000-0002-4266-9197", "clpid": "Buss-Marjorie-T" }, { "family_name": "Duan", "given_name": "Mengtong", "clpid": "Duan-Mengtong" }, { "family_name": "Wong", "given_name": "Katie", "clpid": "Wong-Katie" }, { "family_name": "You", "given_name": "Mei Yi", "clpid": "You-Mei-Yi" }, { "family_name": "Sawyer", "given_name": "Daniel P.", "orcid": "0000-0003-2926-191X", "clpid": "Sawyer-Daniel-P" }, { "family_name": "Swift", "given_name": "Margaret B.", "orcid": "0000-0001-9610-0687", "clpid": "Swift-Margaret-B" }, { "family_name": "Dutka", "given_name": "Przemys\u0142aw", "orcid": "0000-0003-3819-1618", "clpid": "Dutka-Przemys\u0142aw" }, { "family_name": "Mittelstein", "given_name": "David R.", "orcid": "0000-0001-8747-0483", "clpid": "Mittelstein-David-R" }, { "family_name": "Jin", "given_name": "Zhiyang", "orcid": "0000-0002-4411-6991", "clpid": "Jin-Zhiyang" }, { "family_name": "Abedi", "given_name": "Mohamad H.", "orcid": "0000-0001-9717-6288", "clpid": "Abedi-Mohamad-H" }, { "family_name": "Farhadi", "given_name": "Arash", "orcid": "0000-0001-9137-8559", "clpid": "Farhadi-Arash" }, { "family_name": "Deshpande", "given_name": "Ramya", "clpid": "Deshpande-Ramya" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "abstract": "A major outstanding challenge in the fields of biological research, synthetic biology and cell-based medicine is the difficulty of visualizing the function of natural and engineered cells noninvasively inside opaque organisms. Ultrasound imaging has the potential to address this challenge as a widely available technique with a tissue penetration of several centimeters and spatial resolution below 100 \u00b5m. Recently, the first genetically encoded acoustic reporters were developed based on bacterial gas vesicles to link ultrasound signals to molecular and cellular function. However, the properties of these first-generation acoustic reporter genes (ARGs) resulted in limited sensitivity and specificity for imaging in the in vivo context. Here, we describe second-generation ARGs with greatly improved acoustic properties and expression characteristics, identified through a phylogenetic screen of candidate gene clusters from diverse bacteria and archaea. The resulting constructs offer major qualitative and quantitative improvements, including much stronger ultrasound contrast, the ability to produce nonlinear signals distinguishable from background tissue, and stable long-term expression. We demonstrate the utility of these next-generation ARGs by imaging in situ gene expression in mouse models of breast cancer and tumor-homing probiotic bacteria, revealing the unique spatial distributions of tumor growth and colonization by therapeutic cells noninvasively in living subjects.", "doi": "10.1101/2021.04.26.441537", "publication_date": "2021-04-28" }, { "id": "authors:mvf58-x0e82", "collection": "authors", "collection_id": "mvf58-x0e82", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190709-073532026", "type": "monograph", "title": "Genetically encoded nanostructures enable acoustic manipulation of engineered cells", "author": [ { "family_name": "Wu", "given_name": "Di", "orcid": "0000-0002-6848-668X", "clpid": "Wu-Di" }, { "family_name": "Baresch", "given_name": "Diego", "orcid": "0000-0002-8491-8542", "clpid": "Baresch-D" }, { "family_name": "Cook", "given_name": "Colin", "orcid": "0000-0002-6283-5105", "clpid": "Cook-C" }, { "family_name": "Malounda", "given_name": "Dina", "orcid": "0000-0001-7086-9877", "clpid": "Malounda-D" }, { "family_name": "Maresca", "given_name": "David", "orcid": "0000-0002-4921-6406", "clpid": "Maresca-D" }, { "family_name": "Abundo", "given_name": "Maria Paulene", "orcid": "0000-0002-5122-6937", "clpid": "Abundo-M-P" }, { "family_name": "Mittelstein", "given_name": "David Reza", "orcid": "0000-0001-8747-0483", "clpid": "Mittelstein-D-R" }, { "family_name": "Shapiro", "given_name": "Mikhail G.", "orcid": "0000-0002-0291-4215", "clpid": "Shapiro-M-G" } ], "abstract": "The ability to mechanically manipulate and control the spatial arrangement of biological materials is a critical capability in biomedicine and synthetic biology. Ultrasound has the ability to manipulate objects with high spatial and temporal precision via acoustic radiation force, but has not been used to directly control biomolecules or genetically defined cells. Here, we show that gas vesicles (GVs), a unique class of genetically encoded gas-filled protein nanostructures, can be directly manipulated and patterned by ultrasound and enable acoustic control of genetically engineered GV-expressing cells. Due to their differential density and compressibility relative to water, GVs experience sufficient acoustic radiation force to allow these biomolecules to be moved with acoustic standing waves, as demonstrated within microfluidic devices. Engineered variants of GVs differing in their mechanical properties enable multiplexed actuation and act as sensors of acoustic pressure. Furthermore, when expressed inside genetically engineered bacterial cells, GVs enable these cells to be selectively manipulated with sound waves, allowing patterning, focal trapping and translation with acoustic fields. This work establishes the first genetically encoded nanomaterial compatible with acoustic manipulation, enabling molecular and cellular control in a broad range of contexts.", "doi": "10.1101/691105", "publication_date": "2019-07-06" } ]