Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides consisting of multiple glucose subunits. CDs are widely used in host-guest chemistry and biochemistry due to their structural advantages, biocompatibility, and ability to form inclusion complexes. Recently, CDs have become of high interest in the field of medical imaging as a potential scaffold for the development of a large variety of the contrast agents suitable for magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, positron emission tomography, single photon emission computed tomography, and computed tomography.
View Article and Find Full Text PDFA decacationic water-soluble pillar[5]arene possessing a nonsolvated hydrophobic core has been designed and synthesized. This supramolecular host is capable of binding xenon, as evidenced by hyperCEST depletion experiments. Fluorescence-based studies also demonstrate that xenon binds into the cavity of the pillararene with an association constant of 4.
View Article and Find Full Text PDFDiagnostics (Basel)
August 2020
Perfusion measurements can provide vital information about the homeostasis of an organ and can therefore be used as biomarkers to diagnose a variety of cardiovascular, renal, and neurological diseases. Currently, the most common techniques to measure perfusion are O positron emission tomography (PET), xenon-enhanced computed tomography (CT), single photon emission computed tomography (SPECT), dynamic contrast enhanced (DCE) MRI, and arterial spin labeling (ASL) MRI. Here, we show how regional perfusion can be quantitively measured with magnetic resonance imaging (MRI) using time-resolved depolarization of hyperpolarized (HP) xenon-129 (Xe), and the application of this approach to detect changes in cerebral blood flow (CBF) due to a hemodynamic response in response to brain stimuli.
View Article and Find Full Text PDFPurpose: To test octafluorocyclobutane (OFCB) as an inhalation contrast agent for fluorine-19 MRI of the lung, and to compare the image quality of OFCB scans with perfluoropropane (PFP) scans THEORY AND METHODS: After normalizing for the number of signal averages, a theoretical comparison between the OFCB signal-to-noise ratio (SNR) and PFP SNR predicted the average SNR advantage of 90% using OFCB during gradient echo imaging. The OFCB relaxometry was conducted using single-voxel spectroscopy and spin-echo imaging. A comparison of OFCB and PFP SNRs was performed in vitro and in vivo.
View Article and Find Full Text PDFBiomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD.
View Article and Find Full Text PDFHyperpolarized (HP) Xe magnetic resonance imaging (MRI) is a novel iteration of traditional MRI that relies on detecting the spins of H. Since Xe is a gaseous signal source, it can be used for lung imaging. Additionally, Xe dissolves in the blood stream and can therefore be detectable in the brain parenchyma and vasculature.
View Article and Find Full Text PDFHyperpolarized (HP) xenon-129 (Xe) magnetic resonance (MR) imaging has the potential to detect biological analytes with high sensitivity and high resolution when coupled with xenon-encapsulating molecular probes. Despite the development of numerous HP Xe probes, one of the challenges that has hampered the translation of these agents from in vitro demonstration to in vivo testing is the difficulty in synthesizing the Xe-encapsulating cage molecule. In this study, we demonstrate that a pseudorotaxane, based on a γ-cyclodextrin macrocycle, is easily synthesized in one step and is detectable using HyperCEST-enhanced Xe MR spectroscopy.
View Article and Find Full Text PDFThe field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most influential research reports in the field of AD since 2010. JAD readers were asked to vote on these most influential reports.
View Article and Find Full Text PDFThe field of Alzheimer's disease (AD) research has grown exponentially over the past few decades, especially since the isolation and identification of amyloid-β from postmortem examination of the brains of AD patients. Recently, the Journal of Alzheimer's Disease (JAD) put forth approximately 300 research reports which were deemed to be the most influential research reports in the field of AD since 2010. JAD readers were asked to vote on these most influential reports.
View Article and Find Full Text PDFJ Alzheimers Dis
February 2018
This is the second part of a three-part review series reviewing the most important advances in Alzheimer's disease (AD) research since 2010. This review covers the latest research on genetics and epidemiology. Epidemiological and genetic studies are revealing important insights into the etiology of, and factors that contribute to AD, as well as areas of priority for research into mechanisms and interventions.
View Article and Find Full Text PDFThe Hyperpolarized gas Chemical Exchange Saturation Transfer (HyperCEST) Magnetic Resonance (MR) technique has the potential to increase the sensitivity of a hyperpolarized xenon-129 MRI contrast agent. Signal enhancement is accomplished by selectively depolarizing the xenon within a cage molecule which, upon exchange, reduces the signal in the dissolved phase pool. Herein we demonstrate the in vivo detection of the cucurbit[6]uril (CB6) contrast agent within the vasculature of a living rat.
View Article and Find Full Text PDFContrast Media Mol Imaging
July 2016
Xenon based biosensors have the potential to detect and localize biomarkers associated with a wide variety of diseases. The development and nuclear magnetic resonance (NMR) characterization of cage molecules which encapsulate hyperpolarized xenon is imperative for the development of these xenon biosensors. We acquired (129) Xe NMR spectra, and magnetic resonance images and a HyperCEST saturation map of cucurbit[6]uril (CB6) in whole bovine blood.
View Article and Find Full Text PDFThe presence of trace concentrations of metallic ions, such as copper and zinc, has previously been shown to drastically increase the aggregation rate and neurotoxicity of amyloid-β (Aβ), the peptide implicated in Alzheimer's disease (AD). The mechanism of why copper and zinc accelerate Aβ aggregation is poorly understood. In this work, we use single molecule force spectroscopy (SMFS) to probe the kinetic and thermodynamic parameters (dissociation constant, Kd, kinetic dissociation rate, koff, and free energy, ΔG) of the dissociation of an Aβ dimer, the amyloid species which initiates the amyloid cascade.
View Article and Find Full Text PDFAlzheimer's disease is a neurodegenerative disease with no known cure and few effective treatment options. The principal neurotoxic agent is an oligomeric form of the amyloid-β peptide and one of the treatment options currently being studied is the inhibition of amyloid aggregation. In this work, we test a novel pseudopeptidic aggregation inhibitor designated as SG1.
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