Multi-beam scan analysis with a clinical LINAC for high resolution Cherenkov-excited molecular luminescence imaging in tissue

Abstract

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. Just as in fluorescence microscopy, the choice of excitation geometry can affect the imaging time, spatial resolution and contrast recovered. In this study, the use of spatially patterned illumination was systematically studied comparing scan shapes, starting with line scan and block patterns and increasing from single beams to multiple parallel beams and then to clinically used treatment plans for radiation therapy. The image recovery was improved by a spatial-temporal modulation-demodulation method, which used the ability to capture simultaneous images of the excitation Cherenkov beam shape to deconvolve the CELSI images. Experimental studies used the multi-leaf collimator on a clinical linear accelerator (LINAC) to create the scanning patterns, and image resolution and contrast recovery were tested at different depths of tissue phantom material. As hypothesized, the smallest illumination squares achieved optimal resolution, but at the cost of lower signal and slower imaging time. Having larger excitation blocks provided superior signal but at the cost of increased radiation dose and lower resolution. Increasing the scan beams to multiple block patterns improved the performance in terms of image fidelity, lower radiation dose and faster acquisition. The spatial resolution was mostly dependent upon pixel area with an optimized side length near 38mm and a beam scan pitch of P = 0.33, and the achievable imaging depth was increased from 14mm to 18mm with sufficient resolving power for 1mm sized test objects. As a proof-of-concept, in-vivo tumor mouse imaging was performed to show 3D rendering and quantification of tissue pO2 with values of 5.6mmHg in a tumor and 77mmHg in normal tissue.

Cherenkov‐excited luminescence scanned imaging using scanned beam differencing and iterative deconvolution in dynamic plan radiation delivery in a human breast phantom geometry

“…It can be seen that the DW result presented degraded image fidelity with lower signal‐to‐background contrast recovery. This can be explained by the fact that, in comparison with the IMRT plan, much more radiation dose of the DW plan was delivered with a fixed beam shape, which means the difference operations would result in zero Cherenkov and luminescence for this part of dose . To investigate lateral spatial resolution, Z‐profiles along the white dashed lines in Fig.…”

“…In supplement to this, this study focused on a method for high resolution CELSI recovery to image mesoscopic biological structures (e.g., subcutaneous blood capillaries and lymphatics) testing for Ø = 0.5 mm as used in the phantom experiments. Based upon our previous conclusion from studying patterned illumination, that is, that the SNR for induced luminescence is proportional to the target area covered within the irradiation beam, the advantage of IMRT or DW scanning come in with large areas providing large signals for detection. As discussed before, downsized beam could be achieved by an original edge‐scanned irradiation, and thus the edges should sweep over the target.…”

“…(b) that spatial resolutions improve in the progression from edge‐scanning to line‐scanning, as expected. However, much more noise can be found for the case of b = 1, because of the strong positive dependency of signal‐to‐noise ratio (SNR) on the x‐ray beam size in CELSI . Consequently, we started the iterative deconvolution procedure from a large beamlet size.…”

“…In this paper, a novel iterative deconvolution method is proposed for CELSI with an edge‐scanned excitation beam. Since smaller beam sizes have been demonstrated to produce higher spatial resolution for CELSI, in this method, raw Cherenkov measurements were iteratively differenced to form width‐reduced effective excitations (termed as beamlets), improving the sensitivity to high spatial frequency data. The resultant stepwise widened frequency band renders a potential way for a converged iteration process towards a realistic result with broadband frequency.…”

Tracking tumor radiotherapy response in vivo with Cherenkov-excited luminescence ink imaging

“…The information gained in positron emission tomography (PET), for example, can observe tumor properties such as cell metabolic activity and hypoxia with the use of radiotracers like 18 F-fluoro-deoxyglucose 8 . Perhaps the closest imaging technology to this work is diffusionweighted magnetic resonance imaging (MRI), which can quantify the rate of microscopic water diffusion in vivo and is a promising technique for radiation response evaluation since cell membrane integrity is part of what is imaged here 9,10 .…”