Dataset Information

Multiplexed 129Xe HyperCEST MRI Detection of Genetically Reconstituted Bacterial Protein Nanoparticles in Human Cancer Cells.

ABSTRACT: Gas vesicle nanoparticles (GVs) are gas-containing protein assemblies expressed in bacteria and archaea. Recently, GVs have gained considerable attention for biotechnological applications as genetically encodable contrast agents for MRI and ultrasonography. However, at present, the practical use of GVs is hampered by a lack of robust methodology for their induction into mammalian cells. Here, we demonstrate the genetic reconstitution of protein nanoparticles with characteristic bicone structures similar to natural GVs in a human breast cancer cell line KPL-4 and genetic control of their size and shape through expression of reduced sets of humanized gas vesicle genes cloned into Tol2 transposon vectors, referencing the natural gas vesicle gene clusters of the cyanobacteria planktothrix rubescens/agardhii. We then report the utility of these nanoparticles as multiplexed, sensitive, and genetically encoded contrast agents for hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) MRI.

SUBMITTER: Mizushima R

PROVIDER: S-EPMC7091528 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Multiplexed <sup>129</sup>Xe HyperCEST MRI Detection of Genetically Reconstituted Bacterial Protein Nanoparticles in Human Cancer Cells.

Mizushima Ryota R Inoue Kanako K Fujiwara Hideaki H Iwane Atsuko H AH Watanabe Tomonobu M TM Kimura Atsuomi A

Contrast media & molecular imaging 20200312

Gas vesicle nanoparticles (GVs) are gas-containing protein assemblies expressed in bacteria and archaea. Recently, GVs have gained considerable attention for biotechnological applications as genetically encodable contrast agents for MRI and ultrasonography. However, at present, the practical use of GVs is hampered by a lack of robust methodology for their induction into mammalian cells. Here, we demonstrate the genetic reconstitution of protein nanoparticles with characteristic bicone structures ...[more]

PMID: 32256252

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Project description:Magnetic resonance (MR) imaging and spectroscopy using dissolved hyperpolarized (HP) 129Xe have expanded the ability to probe lung function regionally and noninvasively. In particular, HP 129Xe imaging has been used to quantify impaired gas uptake by the pulmonary tissues. Whole-lung spectroscopy has also been used to assess global cardiogenic oscillations in the MR signal intensity originating from 129Xe dissolved in the red blood cells of pulmonary capillaries. Herein, we show that the magnitude of these cardiogenic dynamics can be mapped three dimensionally using radial MRI, because dissolved 129Xe dynamics are encoded directly in the raw imaging data. Specifically, 1-point Dixon imaging is combined with postacquisition keyhole image reconstruction to assess regional blood volume fluctuations within the pulmonary microvasculature throughout the cardiac cycle. This "oscillation mapping" was applied in healthy subjects (mean amplitude 9% of total RBC signal) and patients with pulmonary arterial hypertension (PAH; mean 4%) and idiopathic pulmonary fibrosis (IPF; mean 14%). Whole-lung mean values from these oscillation maps correlated strongly with spectroscopy and clinical pulmonary function testing, but exhibited significant regional heterogeneity, including gravitationally dependent gradients in healthy subjects. Moreover, regional oscillations were found to be sensitive to disease state. Greater percentages of the lungs exhibit low-amplitude oscillations in PAH patients, and longitudinal imaging shows high-amplitude oscillations increase significantly over time (4-14 mo, P = 0.02) in IPF patients. This technique enables regional dynamics within the pulmonary capillary bed to be measured, and in doing so, provides insight into the origin and progression of pathophysiology within the lung microvasculature.NEW & NOTEWORTHY Spatially heterogeneous abnormalities within the lung microvasculature contribute to pathology in various cardiopulmonary diseases but are difficult to assess noninvasively. Hyperpolarized 129Xe MRI is a noninvasive method to probe lung function, including regional gas exchange between pulmonary air spaces and capillaries. We show that cardiogenic oscillations in the raw dissolved 129Xe MRI signal from pulmonary capillary red blood cells can be imaged using a postacquisition reconstruction technique, providing a new means of assessing regional lung microvasculature function and disease state.

Project description:BackgroundIn patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood.PurposeTo determine the relationship of persistent symptoms and exercise limitation with xenon 129 (129Xe) MRI and CT pulmonary vascular measurements in individuals with PACS.Materials and methodsIn this prospective study, patients with PACS aged 18-80 years with a positive polymerase chain reaction COVID-19 test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLco), 129Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 and underwent spirometry, DLco, and 129Xe MRI. The 129Xe MRI red blood cell (RBC) to alveolar-barrier signal ratio, RBC area under the receiver operating characteristic curve (AUC), CT volume of pulmonary vessels with cross-sectional area 5 mm2 or smaller (BV5), and total blood volume were quantified. St George's Respiratory Questionnaire, International Physical Activity Questionnaire, and modified Borg Dyspnea Scale measured quality of life, exercise limitation, and dyspnea. Differences between groups were compared with use of Welch t-tests or Welch analysis of variance. Relationships were evaluated with use of Pearson (r) and Spearman (ρ) correlations.ResultsForty participants were evaluated, including six controls (mean age ± SD, 35 years ± 15, three women) and 34 participants with PACS (mean age, 53 years ± 13, 18 women), of whom 22 were never hospitalized. The 129Xe MRI RBC:barrier ratio was lower in ever-hospitalized participants (P = .04) compared to controls. BV5 correlated with RBC AUC (ρ = .44, P = .03). The 129Xe MRI RBC:barrier ratio was related to DLco (r = .57, P = .002) and forced expiratory volume in 1 second (ρ = .35, P = .03); RBC AUC was related to dyspnea (ρ = -.35, P = .04) and International Physical Activity Questionnaire score (ρ = .45, P = .02).ConclusionXenon 129 (129Xe) MRI measurements were lower in participants previously infected with COVID-19 who were admitted to in-patient treatment in hospital with post-acute COVID-19 syndrome, 34 weeks ± 25 after infection compared to controls. The 129Xe MRI measures were associated with CT pulmonary vascular density, diffusing capacity of the lung for carbon monoxide, exercise capacity, and dyspnea. Clinical trial registration no.: NCT04584671 © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Wild and Collier in this issue.

Dataset Information

Multiplexed 129Xe HyperCEST MRI Detection of Genetically Reconstituted Bacterial Protein Nanoparticles in Human Cancer Cells.

Publications

Multiplexed <sup>129</sup>Xe HyperCEST MRI Detection of Genetically Reconstituted Bacterial Protein Nanoparticles in Human Cancer Cells.

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