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Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.

ABSTRACT: Ischaemic heart disease evokes a complex immune response. However, tools to track the systemic behaviour and dynamics of leukocytes non-invasively in vivo are lacking. Here, we present a multimodal hot-spot imaging approach using an innovative high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload (19F-HDL) to allow myeloid cell tracking by 19F magnetic resonance imaging. The 19F-HDL nanotracer can additionally be labelled with zirconium-89 and fluorophores to detect myeloid cells by in vivo positron emission tomography imaging and optical modalities, respectively. Using our nanotracer in atherosclerotic mice with myocardial infarction, we observed rapid myeloid cell egress from the spleen and bone marrow by in vivo 19F-HDL magnetic resonance imaging. Concurrently, using ex vivo techniques, we showed that circulating pro-inflammatory myeloid cells accumulated in atherosclerotic plaques and at the myocardial infarct site. Our multimodality imaging approach is a valuable addition to the immunology toolbox, enabling the study of complex myeloid cell behaviour dynamically.

SUBMITTER: Senders ML

PROVIDER: S-EPMC7416336 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.

Senders Max L ML Meerwaldt Anu E AE van Leent Mandy M T MMT Sanchez-Gaytan Brenda L BL van de Voort Jan C JC Toner Yohana C YC Maier Alexander A Klein Emma D ED Sullivan Nathaniel A T NAT Sofias Alexandros Marios AM Groenen Hannah H Faries Christopher C Oosterwijk Roderick S RS van Leeuwen Esther M EM Fay Francois F Chepurko Elena E Reiner Thomas T Duivenvoorden Raphael R Zangi Lior L Dijkhuizen Rick M RM Hak Sjoerd S Swirski Filip K FK Nahrendorf Matthias M Pérez-Medina Carlos C Teunissen Abraham J P AJP Fayad Zahi A ZA Calcagno Claudia C Strijkers Gustav J GJ Mulder Willem J M WJM

Nature nanotechnology 20200420 5

Ischaemic heart disease evokes a complex immune response. However, tools to track the systemic behaviour and dynamics of leukocytes non-invasively in vivo are lacking. Here, we present a multimodal hot-spot imaging approach using an innovative high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload (19F-HDL) to allow myeloid cell tracking by 19F magnetic resonance imaging. The 19F-HDL nanotracer can additionally be labelled with zirconium ...[more]

PMID: 32313216

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Project description:Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.

Dataset Information

Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.

Publications

Probing myeloid cell dynamics in ischaemic heart disease by nanotracer hot-spot imaging.

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