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Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents.

ABSTRACT: Hyperpolarized (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 ?-cyclodextrin macrocycle, is easily synthesized in one step and is detectable using HyperCEST-enhanced ¹²⁹Xe MR spectroscopy.

SUBMITTER: Hane FT

PROVIDER: S-EPMC6641221 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents.

Hane Francis T FT Fernando Ashvin A Prete Braedan R J BRJ Peloquin Brianna B Karas Scott S Chaudhuri Sauradip S Chahal Simrun S Shepelytskyi Yurii Y Wade Alanna A Li Tao T DeBoef Brenton B Albert Mitchell S MS

ACS omega 20180119 1

Hyperpolarized (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 pseudorotax ...[more]

PMID: 31457922

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Project description:PURPOSE:To derive lobar ventilation in patients with chronic obstructive pulmonary disease (COPD) using a rapid time-series hyperpolarized xenon-129 (HPX) magnetic resonance imaging (MRI) technique and compare this to ventilation/perfusion single-photon emission computed tomography (V/Q-SPECT), correlating the results with high-resolution computed tomography (CT) and pulmonary function tests (PFTs). MATERIALS AND METHODS:Twelve COPD subjects (GOLD stages I-IV) participated in this study and underwent HPX-MRI, V/Q-SPECT/CT, high-resolution CT, and PFTs. HPX-MRI was performed using a novel time-series spiral k-space sampling approach. Relative percentage ventilations were calculated for individual lobe for comparison to the relative SPECT lobar ventilation and perfusion. The absolute HPX-MRI percentage ventilation in each lobe was compared to the absolute CT percentage emphysema score calculated using a signal threshold method. Pearson's correlation and linear regression tests were performed to compare each imaging modality. RESULTS:Strong correlations were found between the relative lobar percentage ventilation with HPX-MRI and percentage ventilation SPECT (r?=?0.644; p?<?0.001) and percentage perfusion SPECT (r?=?0.767; p?<?0.001). The absolute CT percentage emphysema and HPX percentage ventilation correlation was also statistically significant (r?=?0.695, p?<?0.001). The whole lung HPX percentage ventilation correlated with the PFT measurements (FEV1 with r?=?-?0.886, p?<?0.001*, and FEV1/FVC with r?=?-?0.861, p?<?0.001*) better than the whole lung CT percentage emphysema score (FEV1 with r?=?-?0.635, p?=?0.027; and FEV1/FVC with r?=?-?0.652, p?=?0.021). CONCLUSION:Lobar ventilation with HPX-MRI showed a strong correlation with lobar ventilation and perfusion measurements derived from SPECT/CT, and is better than the emphysema score obtained with high-resolution CT. KEY POINTS:• The ventilation hyperpolarized xenon-129 MRI correlates well with ventilation and perfusion with SPECT/CT with the advantage of higher temporal and spatial resolution. • The hyperpolarized xenon-129 MRI correlates with the PFT measurements better than the high-resolution CT with the advantage of avoiding the use of ionizing radiation.

Project description:OBJECTIVES:To investigate the use of a fast dynamic hyperpolarised 129Xe ventilation magnetic resonance imaging (DXeV-MRI) method for detecting and quantifying delayed ventilation in patients with chronic obstructive pulmonary disease (COPD). METHODS:Three male participants (age range 31-43) with healthy lungs and 15 patients (M/F?=?12:3, age range?=?48-73) with COPD (stages II-IV) underwent spirometry tests, quantitative chest computed tomography (QCT), and DXeV-MRI at 1.5-Tesla. Regional delayed ventilation was captured by measuring the temporal signal change in each lung region of interest (ROI) in comparison to that in the trachea. In addition to its qualitative assessment through visual inspection by a clinical radiologist, delayed ventilation was quantitatively captured by calculating a covariance measurement of the lung ROI and trachea signals, and quantified using both the time delay, and the difference between the integrated areas covered by the signal-time curves of the two signals. RESULTS:Regional temporal ventilation, consistent with the expected physiological changes across a free breathing cycle, was demonstrated with DXeV-MRI in all patients. Delayed ventilation was observed in 13 of the 15 COPD patients and involved variable lung ROIs. This was in contrast to the control group, where no delayed ventilation was demonstrated (p =?0.0173). CONCLUSIONS:DXeV-MRI offers a non-invasive way of detecting and quantifying delayed ventilation in patients with COPD, and provides physiological information on regional pulmonary function during a full breathing cycle. KEY POINTS:• Dynamic xenon MRI allows for the non-invasive detection and measurement of delayed ventilation in COPD patients. • Dynamic xenon MRI during a free breathing cycle can provide unique information about pulmonary physiology and pulmonary disease pathophysiology. • With further validation, dynamic xenon MRI could offer a non-invasive way of measuring collateral ventilation which can then be used to guide lung volume reduction therapy (LVRT) for certain COPD patients.

Dataset Information

Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents.

Publications

Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents.

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