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Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging.

ABSTRACT: Low signal-to-noise ratios and limited imaging depths restrict the ability of optical-imaging modalities to detect and accurately quantify molecular emissions from tissue. Here, by using a scanning external X-ray beam from a clinical linear accelerator to induce Cherenkov excitation of luminescence in tissue, we demonstrate in vivo mapping of the oxygenation of tumours at depths of several millimetres, with submillimetre resolution and nanomolar sensitivity. This was achieved by scanning thin sheets of the X-ray beam orthogonally to the emission-detection plane, and by detecting the signal via a time-gated CCD camera synchronized to the radiation pulse. We also show with experiments using phantoms and with simulations that the performance of Cherenkov-excited luminescence scanned imaging (CELSI) is limited by beam size, scan geometry, probe concentration, radiation dose and tissue depth. CELSI might provide the highest sensitivity and resolution in the optical imaging of molecular tracers in vivo.

SUBMITTER: Pogue BW

PROVIDER: S-EPMC6424530 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging.

Pogue Brian W BW Feng Jinchao J LaRochelle Ethan P EP Bruža Petr P Lin Huiyun H Zhang Rongxiao R Shell Jennifer R JR Dehghani Hamid H Davis Scott C SC Vinogradov Sergei A SA Gladstone David J DJ Jarvis Lesley A LA

Nature biomedical engineering 20180413 4

Low signal-to-noise ratios and limited imaging depths restrict the ability of optical-imaging modalities to detect and accurately quantify molecular emissions from tissue. Here, by using a scanning external X-ray beam from a clinical linear accelerator to induce Cherenkov excitation of luminescence in tissue, we demonstrate in vivo mapping of the oxygenation of tumours at depths of several millimetres, with submillimetre resolution and nanomolar sensitivity. This was achieved by scanning thin sh ...[more]

PMID: 30899599

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Project description:PurposeThe purpose of this study was to demonstrate high resolution optical luminescence sensing, referred to as Cherenkov excited luminescence scanning imaging (CELSI), could be achieved during a standard dynamic treatment plan for a whole breast radiotherapy geometry.MethodsThe treatment plan beams induce Cherenkov light within tissue, and this excitation projects through the beam trajectory across the medium, inducing luminescence where there can be molecular reporter. Broad beams generally produce higher signal but low spatial resolution, yet for dynamic plans the scanning of the multileaf collimator allows for a beam-narrowing strategy by recursively temporal differencing each of the Cherenkov images and associated luminescence images. Then reconstruction from each of these size-reduced beamlets defined by the differenced Cherenkov images provides a well-conditioned matrix inversion, where the spatial frequencies are limited by the higher signal-to-noise ratio beamlets. A built-in stepwise convergence relies on stepwise beam size reduction, which is associated with a widening of the bandwidth of Cherenkov spatial frequency and resultant increase in spatial resolution. For the phantom experiments, europium nanoparticles were used as luminescent probes and embedded at depths ranging from 3 to 8 mm. An intensity modulated radiotherapy (IMRT) plan was used to test this.ResultsThe Cherenkov images spatially guided where the luminescence was measured from, providing high lateral resolution, and iterative reconstruction convergence showed that optimization of the initial and stopping beamlet widths could be achieved with 15 and 4.5 mm, respectively, using a luminescence imaging frame rate of 5/s. With the IMRT breast plan, the original lateral resolution was improved 2X, that is, 0.08-0.24 mm for target depths of 3-8 mm. In comparison, a dynamic wedge (DW) plan showed an inferior image fidelity, with relative contrast recovery decreasing from 0.86 to 0.79. The methodology was applied to a three-dimensional dataset to reconstruct Cherenkov excited luminescence intensity distributions showing volumetric recovery of a 0.5 mm diameter object composed of 0.5 μM luminescent microbeads.ConclusionsHigh resolution CELSI was achieved with a clinical breast external beam radiotherapy (EBRT) plan. It is anticipated that this method can allow visualization and localization for luminescence/fluorescence tagged vasculature, lymph nodes, or superficial tagged regions with most dynamic treatment plans.

Dataset Information

Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging.

Publications

Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging.

Similar Datasets

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