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

Abstract

Purpose: This study demonstrates remote imaging for in vivo detection of radiation-induced tumor microstructural changes by tracking the diffusive spread of injected intratumor UV excited tattoo ink using Cherenkov-excited luminescence imaging (CELI). Methods: Micro-liter quantities of luminescent tattoo ink with UV absorption and visible emission were injected at a depth of 2mm into mouse tumors prior to receiving a high dose treatment of radiation. X-rays from a clinical linear accelerator were used to excite phosphorescent compounds within the tattoo ink through Cherenkov emission. The in vivo phosphorescence was detected using a time-gated intensified CMOS camera immediately after injection, and then again at varying time points after the ink had broken down with the apoptotic tumor cells. ex vivo tumors were imaged post-mortem using hyperspectral cryo-fluorescence imaging to quantify necrosis and compared to Cherenkov-excited light imaging of diffusive ink spread measured in vivo. Results: Imaging of untreated control mice showed that ink distributions remained constant after four days with less than 3% diffusive spread measured using full width at 20% max. For all mice, in vivo CELI measurements matched within 12% of the values estimated by the high-resolution ex vivo sliced luminescence imaging of the tumors. The tattoo ink spread in treated mice was found to correlate well with the nonperfusion necrotic core volume (R 2 =0.92) but not well with total tumor volume changes (R 2 =0.34). Conclusion: In vivo and ex vivo findings indicate that the diffusive spread of the injected tattoo ink can be related to radiation-induced necrosis, independent of total tumor volume change. Tracking the diffusive spread of the ink allows for distinguishing between an increase in tumor size due to new cellular growth and an increase in tumor size due to edema. Furthermore, the imaging resolution of CELI allows for in vivo tracking of subtle microenvironmental changes which occur earlier than tumor shrinkage and this offers the potential for novel, minimally invasive radiotherapy response assay without interrupting a singular clinical workflow.

Light flash and odor during proton beam therapy for pediatric patients: a prospective observational study

“…Cherenkov light is thought to be one of the causes of light flash during irradiation, and there are many reports of detection of Cherenkov light during radiation therapy ( 19 – 22 ). Cherenkov light is a pale light, and the light detected in our analyses in pediatric and adult patients was mainly blue and purple, which is consistent with Cherenkov light as the cause of the light flash ( 4 ).…”

Light flashes during proton and photon radiotherapy: A multicenter prospective observational study

“…Some patients who receive radiation therapy complain that a light appears, even when they close their eyes. This phenomenon is referred to as phosphene or more recently as Cherenkov light [1] , [2] , [3] , which is due to visible photons produced when a charged particle travels through a transparent medium at a speed greater than the speed of light in that medium [4] , [5] . Cherenkov light was first observed by Marie Curie in 1910 as a pale blue light from concentrated radium in a dark room [6] , [7] .…”

Maternally transferred monoclonal antibodies protect neonatal mice from herpes simplex virus-induced mortality and morbidity

“…While maternal Abs prevent nHSV mortality and morbidity (12, 29), their biodistribution in pregnant dams has not been fully elucidated. To preserve the complex anatomy of the placental-fetal interface we pursued hyperspectral imaging via whole body cryo-macrotome processing (30), which causes minimal disruption to these tissues (Figure 1). We administered fluorescently labeled UB-621 mAb to pregnant C57BL6 (B6) dams two days before sacrifice and tissue preparation.…”