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Farrar, Christian

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Farrar

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Christian

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Farrar, Christian
Author's Publications: search.filters.isAuthorOfPublication.5f8daae6-44ae-40fc-866f-809b58850594

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    Pulseq‐CEST: Towards multi‐site multi‐vendor compatibility and reproducibility of CEST experiments using an open‐source sequence standard
    (Wiley, 2021-05-07) Herz, Kai; Mueller, Sebastian; Perlman, Or; Zaitsev, Maxim; Knutsson, Linda; Sun, Phillip Zhe; Zhou, Jinyuan; van Zijl, Peter; Heinecke, Kerstin; Schuenke, Patrick; Farrar, Christian; Schmidt, Manuel; Dörfler, Arnd; Scheffler, Klaus; Zaiss, Moritz
    Purpose: As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols. Methods: We present the benefits of such a standard in three ways: (1) an open database on GitHub, where fully defined, human-­readable CEST protocols can be shared; (2) an open-­source Bloch-­McConnell simulation to test and optimize CEST preparation periods in silico; and (3) a hybrid MR sequence that plays out the CEST preparation period and can be combined with any existing readout module. Results: The exact definition of the CEST preparation period, in combination with the flexible simulation, leads to a good match between simulations and measurements. The standard allowed finding consensus on three amide proton transfer–­weighted protocols that could be compared in healthy subjects and a tumor patient. In addition, we could show coherent multisite results for a sophisticated CEST method, highlighting the benefits regarding protocol sharing and reproducibility. Conclusion: With Pulseq-­ CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.
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    RNA Aptamer Probes as Optical Imaging Agents for the Detection of Amyloid Plaques
    (Public Library of Science, 2014) Farrar, Christian; William, Christopher M.; Hudry, Eloise; Hashimoto, Tadafumi; Hyman, Bradley
    Optical imaging using multiphoton microscopy and whole body near infrared imaging has become a routine part of biomedical research. However, optical imaging methods rely on the availability of either small molecule reporters or genetically encoded fluorescent proteins, which are challenging and time consuming to develop. While directly labeled antibodies can also be used as imaging agents, antibodies are species specific, can typically not be tagged with multiple fluorescent reporters without interfering with target binding, and are bioactive, almost always eliciting a biological response and thereby influencing the process that is being studied. We examined the possibility of developing highly specific and sensitive optical imaging agents using aptamer technology. We developed a fluorescently tagged anti-Aβ RNA aptamer, β55, which binds amyloid plaques in both ex vivo human Alzheimer’s disease brain tissue and in vivo APP/PS1 transgenic mice. Diffuse β55 positive halos, attributed to oligomeric Aβ, were observed surrounding the methoxy-XO4 positive plaque cores. Dot blots of synthetic Aβ aggregates provide further evidence that β55 binds both fibrillar and non-fibrillar Aβ. The high binding affinity, the ease of probe development, and the ability to incorporate multiple and multimodal imaging reporters suggest that RNA aptamers may have complementary and perhaps advantageous properties compared to conventional optical imaging probes and reporters.
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    Vessel Architectural Imaging Identifies Cancer Patient Responders to Anti-angiogenic Therapy
    (2013) Emblem, Kyrre E.; Mouridsen, Kim; Bjornerud, Atle; Farrar, Christian; Jennings, Dominique; Borra, Ronald J H; Wen, Patrick; Ivy, Percy; Batchelor, Tracy; Rosen, Bruce; Jain, Rakesh; Sorensen, A. Gregory
    Measurement of vessel caliber by Magnetic Resonance Imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI coined as Vessel Architectural Imaging (VAI) that exploits an intriguing and overlooked temporal shift in the MR signal forming the basis for vessel caliber estimation and show how this phenomenon can reveal new information on vessel type and function not assessed by any other non-invasive imaging technique. We also show how this biomarker can provide novel biological insights into the treatment of cancer patients. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation levels and reduce vessel calibers in patients with recurrent glioblastomas, and more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies.
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    Magneto-Fluorescent Core-Shell Supernanoparticles
    (2014) Chen, Ou; Riedemann, Lars; Etoc, Fred; Herrmann, Hendrik; Coppey, Mathieu; Barch, Mariya; Farrar, Christian; Zhao, Jing; Bruns, Oliver T.; Wei, He; Guo, Peng; Cui, Jian; Jensen, Russ; Chen, Yue; Harris, Daniel K.; Cordero, Jose M.; Wang, Zhongwu; Jasanoff, Alan; Fukumura, Dai; Reimer, Rudolph; Dahan, Maxime; Jain, Rakesh; Bawendi, Moungi G.
    Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface, and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close packed magnetic nanoparticle “core” which is fully surrounded by a “shell” of fluorescent quantum dots. A thin layer of silica-coating provides high colloidal stability and biocompatiblity and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.
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    Molecular MRI of myocardial peroxidase activity in ischemic injury reveals a chemical milieu incompatible with stem cell survival
    (BioMed Central, 2016) Chen, Howard; Chen, Y Iris; Farrar, Christian; Gale, Eric; Caravan, Peter; Liao, Ronglih; Chen, John; Sosnovik, David
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    Redesigned Reporter Gene for Improved Proton Exchange-Based Molecular MRI Contrast
    (Springer Science and Business Media LLC, 2020-11-26) Perlman, Or; Ito, Hirotaka; Gilad, Assaf A.; McMahon, Michael T.; Chiocca, E.; Nakashima, Hiroshi; Farrar, Christian
    Reporter gene imaging allows for non-invasive monitoring of molecular processes in living cells, providing insights on the mechanisms underlying pathology and therapy. A lysine-rich protein (LRP) chemical exchange saturation transfer (CEST) MRI reporter gene has previously been developed and used to image tumor cells, cardiac viral gene transfer, and oncolytic virotherapy. However, the highly repetitive nature of the LRP reporter gene sequence leads to DNA recombination events and the expression of a range of truncated LRP protein fragments, thereby greatly limiting the CEST sensitivity. Here we report the use of a redesigned LRP reporter (rdLRP), aimed to provide excellent stability and CEST sensitivity. The rdLRP contains no DNA repeats or GC rich regions and 30% less positively charged amino-acids. RT-PCR of cell lysates transfected with rdLRP demonstrated a stable reporter gene with a single distinct band corresponding to full-length DNA. A distinct increase in CEST-MRI contrast was obtained in cell lysates of rdLRP transfected cells and in in vivo LRP expressing mouse brain tumors ( p = 0.0275 , n = 10).
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    MR fingerprinting for semisolid magnetization transfer and chemical exchange saturation transfer quantification
    (Wiley, 2022-03-03) Perlman, Or; Farrar, Christian; Heo, Hye‐Young