Radioluminescence Imaging Research Articles

Informing solar blind radioluminescence imaging through a calibrated spectrum

While direct radiation detection methods offer great insight into the origin of ionizing particles and photons, their use to locate contaminated areas or concealed radioactive sources can lead to undue exposure of personnel and equipment to ionizing radiation or the potential for contamination. These same sources induce ultraviolet (UV) optical photon fluorescence in air – a process referred to as radioluminescence – that may be imaged from low dose regions over larger attenuation lengths than ionizing radiation. However, most optical detection methods are limited to low lighting conditions to image the more abundant ultraviolet-A (UV-A) photons. To extend this capability to room light or daytime conditions, the solar blind region (Ultraviolet-C (UV–C), <280 nm) can be tapped. Though the emission yield of UV-C photons is roughly two orders of magnitude lower than that in the UV-A regime, the UV-C offers dramatic improvements in signal-to-noise ratios under bright lighting conditions due to decreased background interferences. The yield of specific UV-C lines, if present in the literature at all, varies widely, which has a large impact in modeling and analyzing standoff UV-C measurement scenarios. Thus, we have captured improved radioluminescence spectra over 250–400 nm and identified observed emission peaks in ambient air. Many of the UV-C photons produced by ionizing radiation excitation result from high-energy, molecular nitrogen Gaydon-Herman transitions which have had limited study to date for this application. Relating these findings to published UV-A yields, we estimate emissions between 0.15 and 0.19 photons/MeV over 250–280 nm. We also use a commercial corona-discharge imaging camera to demonstrate outdoor UV-C radiation mapping of alpha and gamma emitters from 50 to 75 m standoffs, respectively. The imaged “counts” are compared to optically modeled values and show the same trend over distance.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and β-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

Advancements in Remote Alpha Radiation Detection: Alpha-Induced Radio-Luminescence Imaging with Enhanced Ambient Light Suppression.

Heavy nuclides like uranium and their decay products are commonly found in nuclear industries and can pose a significant health risk to humans due to their alpha-emitting properties. Traditional alpha detectors require close contact with the contaminated surface, which can be time-consuming, labour-intensive, and put personnel at risk. Remote detection is urgently needed but very challenging. To this end, a candidate detection mechanism is alpha-induced radio-luminescence. This approach uses the emission of photons from radio-ionised excited nitrogen molecules to imply the presence of alpha emitters from a distance. Herein, the use of this phenomenon to remotely image various alpha emitters with unparalleled levels of sensitivity and spatial accuracy is demonstrated. Notably, the system detected a 29 kBq Am-241 source at a distance of 3 m within 10 min. Furthermore, it demonstrated the capability to discern a 29 kBq source positioned 7 cm away from a 3 MBq source at a 2 m distance. Additionally, a 'sandwich' filter structure is described that incorporates an absorptive filter between two interference filters to enhance the ambient light rejection. The testing of the system is described in different lighting environments, including room light and inside a glovebox. This method promises safer and more efficient alpha monitoring, with applications in nuclear forensics, waste management and decommissioning.

Decolorization, spectral broadening, and luminescence enhancement in Tb:Y2O3 transparent ceramics through vacuum thermal reduction.

Tb3+ is extensively employed in magneto-optical devices and luminescent materials owing to its distinctive physical properties. However, under certain conditions, trivalent Tb3+ readily undergoes oxidation to tetravalent Tb4+, significantly reducing the performance of devices containing Tb3+. In this Letter, we report a technique called dual-annealing (DA) post-treatment, which effectively solves Tb oxidation issues by utilizing the reducibility of the vacuum environment. High-quality Tb:Y2O3 transparent ceramics were prepared with in-line transmittance of ∼80% at 800 nm. Subsequently, the prepared ceramics were subjected to DA treatment. The optical, photoluminescence, radioluminescence, and x-ray imaging properties of DA samples were comprehensively compared with those of conventionally single-annealed (SA) samples. The coloration of Tb:Y2O3 transparent ceramics due to Tb4+ absorption was eliminated by DA. Notably, the DA sample showed a 3.28-fold increase in photoluminescence intensity and a 2.73-fold increase in radioluminescence intensity compared with the traditional SA sample. DA post-treatment enables Tb: Y2O3 transparent ceramics to achieve x-ray imaging capabilities. This Letter presents a simple, efficient, and universally applicable post-treatment technique expected to replace conventional hydrogen annealing in numerous scenarios.

Superior Al90Mg10-Based Composite Fuel Grain for a Hybrid Rocket Engine

A paraffin-based fuel coupled with a nested helical matrix structure is a low-cost, high-performing alternative for hybrid rocket engine applications. The mechanical and combustion properties of the composite fuel grain can be enhanced by replacing the conventional polymer matrix with a metal skeleton. Three-dimensional printing was used to design an Al90Mg10 skeleton embedded with the paraffin-based fuel. The combustion characteristics of the composite fuel grain, including the ignition behavior, pressure oscillations, regression rate, and combustion efficiency, were comprehensively investigated. The properties of grains with and without a secondary perforated structure were compared. The flame structure and metal burning behavior of the hybrid rocket engine were monitored by endoscopic radioluminescence imaging, and the emission spectral characteristics of the plume were analyzed simultaneously. Good flammability makes the Al90Mg10 helical skeleton a promising candidate for enhancing the combustion performance of a paraffin-based fuel grain. The combustion process with rapid ignition was relatively stable, and no additional pressure oscillation frequency was observed. The metal-based composite fuel grains had a superior regression rate to that of a paraffin-based fuel grain (up to 100% higher using the perforated skeleton). Introducing a secondary structure into the fuel grain promoted the reaction and thereby enhanced the combustion performance.

Painted radioluminescence imaging with radioluminescent nanophosphors

Optical strategies like Cerenkov luminescence imaging (CLI) or radioluminescence imaging (RLI) to image clinically available positron emission tomography and single photon emission computed tomography probes still suffer from low sensitivity or resolution. This study investigated a painted radioluminescence imaging (PRLI) approach that employed a painted scintillator to improve signal and resolution for imaging clinical used 18F-fluorinated deoxyribose (18F-FDG). Results of phantom and in vivo experiments revealed that PRLI could achieve ∼100 times higher signal intensity than CLI and higher resolution compared to Flexible radioluminescence imaging (FRLI), a flexible scintillation-based RLI. PRLI increased signal-to-background ratio in the pseudotumor model by 81.8% (compared to CLI) and 73.9% (compared to FRLI) as well as in the tumor model by 60.0% (compared to CLI) and 33.3% (compared to FRLI). As a conclusion, PRLI is a more effective optical approach for detecting tumors using 18F-FDG.

PHSOR11 Presentation Time: 1:20 PM: Verify the Transit Time Correction Accuracy of the Bravos Afterloader System Using a Novel Scintillation-Based Brachytherapy Quality Assurance Device

<h3>Purpose</h3> Compared to the older generations, the new Bravos high dose rate (HDR) afterloader offers the function to automatically correct dwell time to compensate the transit dose effect. To our best knowledge, there is no QA attempt to verify the accuracy of this correction. To address this issue, a new transit time measurement module has been developed and included in the OriQA HDR QA device, an autonomous phantom for HDR brachytherapy quality assurance. In this work, we employ the OriQA system to verify the transit time correction accuracy of the Bravos afterloader system. <h3>Method</h3> The OriQA device utilizes radioluminescence imaging technique to accurately measure HDR source strength, dwell time, and dwell position. It consists of a 20 cm needle applicator insert, a radioluminescence phosphor sheet placed directly atop the applicator, a digital camera, and software for signal processing and displaying results. Radiation-induced luminescence photons are emitted from the phosphor sheet and captured by the camera. The signal intensity and location are processed to yield relative source strength and dwell information. For the verification test, one of the Bravos channels was connected to the OriQA applicator using a one-meter transfer tube. After specific plan delivery, the raw data of OriQA measurement including source position and time was exported to Matlab for further analysis. The real dwell time at each dwell position and the transit time between dwells during cable extension and retraction were extracted. The transit time correction method provided by the vendor was applied to the measurement, yielding the delivered dwell time. The percentage difference between the delivered and planned dwell time was calculated and used as an indicator of the transit time correction accuracy. Several verification plans were created including seven with fixed dwell steps, one with variable dwell steps, and one with variable dwell time. Plans with fixed dwell steps were delivered three times. The rest were delivered once. Plan details are listed in table 1. For each plan, the mean and standard deviation of the difference between planned and delivered dwell time were calculated from all dwell positions and deliveries. <h3>Results</h3> The deviations between the planned and delivered dwell time are listed in table 1. For plans with less than 4 cm dwell step, the accuracy of transit time correction is, on average, less than 1.2% of the dwell time. For plans with 4 cm and 9 cm dwell step, the accuracy is 1.5% and 2.85%, on average, respectively. Dwell time variation does not affect the correction accuracy, as shown in plan 9. Standard deviations of plan 3, 4, and 9 are greater than 1% due to the relatively large difference at the proximal dwell. <h3>Conclusion</h3> This is the first study that successfully verifies the transit time correction accuracy of the Bravos system. Less than 2% accuracy is observed for clinically relevant dwell steps (0.3 cm to 4 cm). Variations in dwell step, dwell position, and dwell time do not worsen the accuracy.

Radioluminescence imaging feasibility for robotic radiosurgery field size quality assurance.

To investigate the feasibility of radioluminescence imaging (RLI) as a novel 2D quality assurance (QA) dosimetry system for CyberKnife®. We developed a field size measurement system based on a commercial complementary metal oxide semiconductor (CMOS) camera facing a radioluminescence screen located at the isocenter normal to the beam axis. The radioluminescence light collected by a lens was used to measure 2D dose distributions. An image transformation procedure, based on two reference phantoms, was developed to correct for projective distortion due to the angle (15°) between the optical and beam axis. Dose profiles were measured for field sizes ranging from 5 mm to 60 mm using fixed circular and iris collimators and compared against gafchromic (GC) film. The corresponding full width at half maximum (FWHM) was measured using RLI and benchmarked against GC film. A small shift in the source-to-surface distance (SSD) of the measurement plane was intentionally introduced to test the sensitivity of the RLI system to field size variations. To assess reproducibility, the entire RLI procedure was tested by acquiring the 60mm circle field three times on two consecutive days. The implemented procedure for perspective image distortion correction showed improvements of up to 1 mm using the star phantom against the square phantom. The FWHM measurements using the RLI system indicated a strong agreement with GC film with maximum absolute difference equal to 0.131 mm for fixed collimators and 0.056 mm for the iris. A 2D analysis of RLI with respect to GC film showed that the differences in the central region are negligible, while small discrepancies are in the penumbra region. Changes in field sizes of 0.2 mm were detectable by RLI. Repeatability measurements of the beam FWHM have shown a standard deviation equal to 0.11mm. The first application of a RLI approach for CyberKnife® field size measurement was presented and tested. Results are in agreement with GC film measurements. Spatial resolution and immediate availability of the data indicate that RLI is a feasible technique for robotic radiosurgeryQA.

3D dose delivery QA using couch and gantry mounted cameras

While 2D planar radiation therapy quality assurance techniques suffice for linac verification, a full 3D dosimetry measurement is ideal for robust treatment plan verification. In this study, an optical 3D dose reconstruction technique based on radioluminescence imaging is presented, using two orthogonal views provided by gantry and couch mounted cameras. Both small field and multi-target beam apertures were tested, mimicking typical 3D radiosurgery plans. Pass rates >94% for 3D gamma with 2%/2mm were achieved in all cases. Slice images were used for gamma analysis in each of transverse, sagittal and coronal planes, through the point of maximum dose. This proposed system can enable real-time imaging of beam delivery dynamics in a cylindrical water-equivalent phantom with high spatial resolution 3D reconstruction of the dose distribution, and verification of each beamlet used.

Radioluminescence Imaging of Drug Elution from Biomedical Implants

AbstractA method to noninvasively measure the concentration of radiolabeled pharmaceuticals on modified drug‐eluting biomedical implant surfaces is described. The implants are coated with microphosphors and radiolabeled pharmaceuticals in a polyurethane film. The drug molecules emit radiation which excites radioluminescence in nearby phosphors; for drug released from the film the radiation is absorbed by the surrounding media and generates no light. The technique is applied to measure beta‐emitting tritium‐labeled vancomycin (3H‐vancomycin) concentration on the surface of an orthopedic plate. Bacteria can coat orthopedic implant surfaces and form biofilms which are resistant to antibiotics and the host's immune system. Antibiotic eluting implant coatings are thus promising candidates for infection prevention and treatment. Radioluminescence imaging permits surface‐specific, noninvasive measurement of drug concentration on implant surfaces, which is an important metric for developing effective drug eluting coatings. The radioluminescence signal increases linearly with 3H‐vancomycin concentration, with a limit of detection (LOD) of 9.6 nCi (3.5 pmol) without tissue. Biomedically relevant drug release concentrations are monitored through 5 mm of porcine tissue slices (38.7 nmol LOD). Despite light scattering, and an eightfold signal decrease through 5 mm of tissue, drug release and reference regions are resolvable for non‐invasive quantification.

Deep learning-augmented radioluminescence imaging for radiotherapy dose verification.

We developed a novel dose verification method using a camera-based radioluminescence imaging system (CRIS) combined with a deep learning-based signal processing technique. The CRIS consists of a cylindrical chamber coated with scintillator material on the inner surface of the cylinder, coupled with a hemispherical mirror and a digital camera at the two ends. After training, the deep learning model is used for image-to-dose conversion to provide absolute dose prediction at multiple depths of a specific water phantom from a single CRIS image under the assumption of a good consistency between the TPS setting and actual beam energy. The model was trained using a set of captured radioluminescence images and the corresponding dose maps from the clinical treatment planning system (TPS) for the sake of acceptable data collection. To overcome the latent error and inconsistency that exists between the TPS calculation and the corresponding measurement, the model was trained in an unsupervised manner. Validation experiments were performed on five square fields (ranging from 2 × 2 to 10 × 10cm2 ) and three clinical intensity-modulated radiation therapy (IMRT) cases. The results were compared to the TPS calculations in terms of gamma index at 1.5, 5, and 10cm depths. The mean 2%/2mm gamma pass rates were 100% for square fields and 97.2% (range from 95.5% to 99.5%) for the IMRT fields. Further validations were performed by comparing the CRIS results with measurements on various regular fields. The results show a mean gamma pass rate of 91% (1%/1mm) for cross-profiles and a mean percentage deviation of 1.15% for percentage depth doses (PDDs). The system is capable of converting the irradiated radioluminescence image to corresponding water-based dose maps at multiple depths with a spatial resolution comparable to the TPS calculations.

Compositional screening of Ce-doped (Gd,Lu,Y)3(Al,Ga)5O12 ceramics prepared by quenching from melt and their luminescence properties

Quenching from the melt using an Optical Floating Zone furnace was investigated as a possible high-throughput preparation method in order to screen novel scintillating materials. To validate this method, polycrystalline rare-earth aluminum garnets and yttrium gallium aluminum garnets were synthesized and characterized by X-ray diffraction, photoluminescence and radioluminescence emission spectra as well as radioluminescence imaging and compared to the previously reported properties of those materials. In order to achieve rapid, but quantitative comparison of the materials, pellets fabricated from the synthesized powders were sintered; two different sintering conditions were investigated and compared. A simplistic energy deposition and light absorption model for brightness of opaque samples under X-ray irradiation was developed to estimate the relative scintillation efficiency of the materials. Based on the results, Y3Al5O12, LuY2Al5O12 and GdY2Al5O12 seem to have the highest scintillation efficiency among the prepared samples.

Spatial and temporal dosimetry of individual electron FLASH beam pulses using radioluminescence imaging

Purpose. In this study, spatio-temporal beam profiling for electron ultra-high dose rate (UHDR; >40 Gy s−1) radiation via Cherenkov emission and radioluminescence imaging was investigated using intensified complementary metal–oxide–semiconductor cameras. Methods. The cameras, gated to FLASH optimized linear accelerator pulses, imaged radioluminescence and Cherenkov emission incited by single pulses of a UHDR (>40 Gy s−1) 10 MeV electron beam delivered to the isocenter. Surface dosimetry was investigated via imaging Cherenkov emission or scintillation from a solid water phantom or Gd2O2S:Tb screen positioned on top of the phantom, respectively. Projected depth–dose profiles were imaged from a tank filled with water (Cherenkov emission) and a 1 g l−1 quinine sulfate solution (scintillation). These optical results were compared with projected lateral dose profiles measured by Gafchromic film at different depths, including the surface. Results. The per-pulse beam output from Cherenkov imaging agreed with the photomultiplier tube Cherenkov output to within 3% after about the first five to seven ramp-up pulses. Cherenkov emission and scintillation were linear with dose (R 2 = 0.987 and 0.995, respectively) and independent of dose rate from ∼50 to 300 Gy s−1 (0.18–0.91 Gy/pulse). The surface dose distribution from film agreed better with scintillation than with Cherenkov emission imaging (3%/3 mm gamma pass rates of 98.9% and 88.8%, respectively). Using a 450 nm bandpass filter, the quinine sulfate-based water imaging of the projected depth optical profiles agreed with the projected film dose to within 5%. Conclusion. The agreement of surface dosimetry using scintillation screen imaging and Gafchromic film suggests it can verify the consistency of daily beam quality assurance parameters with an accuracy of around 2% or 2 mm. Cherenkov-based surface dosimetry was affected by the target’s optical properties, prompting additional calibration. In projected depth–dose profiling, scintillation imaging via spectral suppression of Cherenkov emission provided the best match to film. Both camera-based imaging modalities resolved dose from single UHDR beam pulses of up to 60 Hz repetition rate and 1 mm spatial resolution.

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model.

The increased glucose metabolism of cancer cells is the basis for 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, due to its coarse image resolution, PET is unable to resolve the metabolic role of cancer-associated stroma, which often influences the metabolic reprogramming of a tumor. This study investigates the use of radioluminescence microscopy for imaging FDG uptake in engineered 3D tumor models with high resolution. Multicellular tumor spheroids (A549 lung adenocarcinoma) were co-cultured with GFP-expressing human umbilical vein endothelial cells (HUVECs) within an artificial extracellular matrix to mimic a tumor and its surrounding stroma. The tumor model was constructed as a 200-μm-thin 3D layer over a transparent CdWO4 scintillator plate to allow high-resolution imaging of the cultured cells. After incubation with FDG, the radioluminescence signal was collected by a highly sensitive widefield microscope. Fluorescence microscopy was performed using the same instrument to localize endothelial and tumor cells. Simultaneous and co-localized brightfield, fluorescence, and radioluminescence imaging provided high-resolution information on the distribution of FDG in the engineered tissue. The microvascular stromal compartment as a whole took up a large fraction of the FDG, comparable to the uptake of the tumor spheroids. In vitro gamma counting confirmed that A549 and HUVEC cells were both highly glycolytic with rapid FDG uptake kinetics. Despite the relative thickness of the tissue constructs, an average spatial resolution of 64 ± 4μm was achieved for imaging FDG. Our study demonstrates the feasibility of imaging the distribution of FDG uptake in engineered in vitro tumor models. With its high spatial resolution, the method can separately resolve tumor and stromal components. The approach could be extended to more advanced engineered cancer models but also to surgical tissue slices and tumor biopsies.

Deep learning-augmented radiotherapy visualization with a cylindrical radioluminescence system

This study aims to demonstrate a low-cost camera-based radioluminescence imaging system (CRIS) for high-quality beam visualization that encourages accurate pre-treatment verifications on radiation delivery in external beam radiotherapy. To ameliorate the optical image that suffers from mirror glare and edge blurring caused by photon scattering, a deep learning model is proposed and trained to learn from an on-board electronic portal imaging device (EPID). Beyond the typical purposes of an on-board EPID, the developed system maintains independent measurement with co-planar detection ability by involving a cylindrical receptor. Three task-aware modules are integrated into the network design to enhance its robustness against the artifacts that exist in an EPID running at the cine mode for efficient image acquisition. The training data consists of various designed beam fields that were modulated via the multi-leaf collimator (MLC). Validation experiments are performed for five regular fields ranging from 2 × 2 cm2 to 10 × 10 cm2 and three clinical IMRT cases. The captured CRIS images are compared to the high-quality images collected from an EPID running at the integration-mode, in terms of gamma index and other typical similarity metrics. The mean 2%/2 mm gamma pass rate is 99.14% (range between 98.6% and 100%) and 97.1% (ranging between 96.3% and 97.9%), for the regular fields and IMRT cases, respectively. The CRIS is further applied as a tool for MLC leaf-end position verification. A rectangular field with introduced leaf displacement is designed, and the measurements using CRIS and EPID agree within 0.100 mm ± 0.072 mm with maximum of 0.292 mm. Coupled with its simple system design and low-cost nature, the technique promises to provide viable choice for routine quality assurance in radiation oncology practice.

Scintillation materials based on metal iodates by rare earth doping modifications for use in radioluminescence and X-ray imaging

We obtained metal iodates scintillators with high X-ray response and scintillating films with high X-ray sensitivity and imaging spatial resolution.

Automated multi-parameter high-dose-rate brachytherapy quality assurance via radioluminescence imaging

The purpose of this study is to leverage radioluminescence imaging for the development of an automated high-dose-rate (HDR) brachytherapy quality assurance (QA) system that enables simultaneous measurements of dwell position, dwell time, wire velocity, and relative source strength in a single test. The system consists of a radioluminescence phosphor sheet (a mixture of Gd2O2S:Tb and PDMS) positioned atop a HDR needle applicator, a complementary metal-oxide-semiconductor digital camera used to capture the emitted radioluminescence signals from the scintillator sheet, and an in-house graphical user interface for signal processing. The signal processing was used to extract source intensity, location, and elapsed time, yielding the final measurements on dwell position, dwell time, and wire velocity. The source strength relative to the well chamber calibration (in unit of Air-Kerma strength, Sk ) is measured by establishing a calibration curve that correlates Sk with the detector response. Validation experiments are performed using three customized treatment plans. With these plans, the dwell position and dwell time are verified for a range of 110.0 cm–117.5 cm and 2 s–16 s, respectively, and the linear correlation with Sk is demonstrated for the source strength varying between 28 348 U (cGy cm2 h−1) and 41 906 U. The wire velocity, i.e. the speed of the radioactive source averaged over the distance in between dwell positions, is calculated for various distances ranging from 5 mm to 50 mm. Results show that the mean deviations of the measured dwell position and dwell time are 0.1 mm (range from 0 to 0.2 mm) and 32.5 ms (range from 0 to 60.0 ms) with respect to the planned values, respectively, and the system response is highly linear with Sk ( R2 = 0.998). Moreover, the measured wire velocities are comparable to previously reported values. Benefitting from the compact hardware design and image processing algorithms, the system provides a practical, reliable, and comprehensive solution for HDR QA.

Small animal irradiator dose distribution verification using radioluminescence imaging.

The main objective of this work was the development of a novel 2D dosimetry approach for small animal external radiotherapy using radioluminescence imaging (RLI) with a commercial complementary metal oxide semiconductor detector. Measurements of RLI were performed on the small animal image-guided platform SmART, RLI data were corrected for perspective distortion using Matlab. Four irradiation fields were tested and the planar 2D dose distributions and dose profiles were compared against dose calculations performed with a Monte Carlo based treatment planning system and gafchromic film. System linearity and RLI image noise against dose were also measured. The maximum difference between beam size measured with RLI and nominal beam size was less than 8% for all the tested beams. The image correction procedure was able to reduce perspective distortion. A novel RLI approach for quality assurance of a small animal irradiator was presented and tested. Results are in agreement with MC dose calculations and gafchromic film measurements.

PEGylated β-NaGdF4/Tb@CaF2 Core/Shell Nanophosphors for Enhanced Radioluminescence and Folate Receptor Targeting

Lanthanide-doped nanocrystals have been examined extensively as contrast agents for various optical molecular imaging techniques. One of the greatest strengths of these nanomaterials is their ability to enable novel imaging modalities, such as X-ray excited radioluminescence imaging, which leverages the exceptional tissue depth penetration of X-rays and reduced tissue autofluorescence. Here, we report a uniquely engineered NaGdF4/Tb@CaF2 nanoscintillator with substantial lattice mismatch through integration of coprecipitation and thermal decomposition synthetic routes. We observed greatly enhanced radioluminescence by the NaGdF4/15%Tb@CaF2 core/shell nanocrystals, which results from the minimized surface quenching and localized structure transformation. Polyethylene glycol coated NaGdF4/15%Tb@CaF2 nanocrystals demonstrated robust aqueous colloidal stability and were well tolerated by a panel of cell lines. The core/shell NaGdF4/15%Tb@CaF2 nanophosphors were subsequently decorated with targeting folate ligands and investigated as an X-ray luminescence imaging probe in vitro. Overall, the results suggest that these optimized radioluminescent nanophosphors have the potential to enable X-ray excited optical emission for biological imaging and serve as energy mediators in theranostic applications.

In Vivo Translation of the CIRPI System: Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques.

Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging and photoacoustic tomography (PAT). The probe's CaF2:Eu-based scintillating imaging window captures radioluminescence images (360° view) of plaques by detecting β-particles during 18F-FDG decay. A tunable laser-based PAT characterizes tissue constituents of plaque at 7 different wavelengths-540 and 560 nm (calcification), 920 nm (cholesteryl ester), 1040 nm (phospholipids), 1180 nm (elastin/collagen), 1210 nm (cholesterol), and 1235 nm (triglyceride). A single B-scan is concatenated from 330 A-lines captured during a 360° rotation. The abdominal aorta was imaged in vivo in both atherosclerotic rabbits (Watanabe Heritable Hyper Lipidemic [WHHL], 13-mo-old male, n = 5) and controls (New Zealand White, n = 2). Rabbits were fasted for 6 h before 5.55 × 107 Bq (1.5 mCi) of 18F-FDG were injected 1 h before the imaging procedure. Rabbits were anesthetized, and the right or left common carotid artery was surgically exposed. An 8 French catheter sheath was inserted into the common carotid artery, and a 0.035-cm (0.014-in) guidewire was advanced to the iliac artery, guided by x-ray fluoroscopy. A bare metal stent was implanted in the dorsal abdominal aorta as a landmark, followed by the 7 French imaging catheters that were advanced up to the proximal stent edge. Our CIRPI and clinical optical coherence tomography (OCT) were performed using pullback and nonocclusive flushing techniques. After imaging with the CIRPI system, the descending aorta was flushed with contrast agent, and OCT images were obtained with a pullback speed of 20 mm/s, providing images at 100 frames/s. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540 and 560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were further verified with the clinical OCT system showing an area of low attenuation filled with lipids within TCFA. PAT images illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. Only 4 rabbits showed both moderate-to-severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with OCT and histochemical analysis. Conclusion: Our novel multimodality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a preclinical rabbit model. This system proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, the system may enhance the clinical evaluation of TCFA, as well as expand our understanding of coronary artery disease.