This PDF file contains the front matter associated with SPIE Proceedings Volume 11224, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

Intraoperative margin assessment during prostate cancer (PCa) surgery might reduce the number of positive surgical margins (PSM). Cerenkov Luminescence Imaging (CLI) based on optical imaging of PET radiopharmaceuticals is suitable for this purpose. Previous CLI research has been conducted with ¹⁸Fluorine, however, ⁶⁸Gallium has more favorable CLI properties and can be coupled to a prostate cancer specific tracer: the prostate-specific membrane antigen (⁶⁸Ga-PSMA). Light yield, resolution and camera sensitivity of ⁶⁸Ga and ¹⁸F for CLI were investigated in a pre-clinical setting. CLI images were acquired using the LightPath system, with an exposure time of 120s, 2×2 binning and 300s, 8×8 binning. Three Eppendorf tubes (1mL) with different radioactivity concentrations (2.5, 10 and 40kBq/mL) of ¹⁸F and ⁶⁸Ga were imaged. For both isotopes, an excellent linear relationship between the radioactivity concentration and detected light yield was observed (R²=0.99). ⁶⁸Ga showed 22× more light yield compared to ¹⁸F, thus enabled lower detectable radioactivity concentration levels (1.2 vs. 23.7kBq/mL). Based on these promising results, a prospective feasibility study for intraoperative prostate cancer specimen CLI measurements with 68Ga-PSMA was designed and the first patients were enrolled in this study. The prostate was imaged ex vivo with the LightPath system ~70 minutes after injection of ~100MBq 68Ga-PSMA. Hotspots on the CLI images were marked for comparison with histopathology and corresponded to a PSM, defined as tumor on ink. In the first patients, CLI correctly identified all patients with a PSM. The encouraging preliminary results motivated for continuation of this trial.

Genetically engineered mouse model(GEMM) that develops pancreatic ductal adenocarcinoma (PDAC) offers an experimental system to advance our understanding of radiotherapy (RT) for pancreatic cancer. Cone beam CT (CBCT)-guided small animal radiation research platform (SARRP) has been developed to mimic the RT used for human. However, we recognized that CBCT is inadequate to localize the PDAC growing in low image contrast environment. We innovated bioluminescence tomography (BLT) to guide SARRP irradiation for in vivo PDAC. Before working on the complex PDAC-GEMM, we first validated our BLT target localization using subcutaneous and orthotopic pancreatic tumor models. Our BLT process involves the animal transport between the BLT system and SARRP. We inserted a titanium wire into the orthotopic tumor as the fiducial marker to track the tumor location and to validate the BLT reconstruction accuracy. Our data shows that with careful animal handling, minimum disturbance for target position was introduced during our BLT imaging procedure(<0.5mm). However, from longitudinal 2D bioluminescence image (BLI) study, the day-to-day location variation for an abdominal tumor can be significant. We also showed that the 2D BLI in single projection setting cannot accurately capture the abdominal tumor location. It renders that 3D BLT with multipleprojection is needed to quantify the tumor volume and location for precise radiation research. Our initial results show the BLT can retrieve the location at 2mm accuracy for both tumor models, and the tumor volume can be delineated within 25% accuracy. The study for the subcutaneous and orthotopic models will provide us valuable knowledge for BLTguided PDAC-GEMM radiation research.

Biomedical imaging techniques are often limited by the loss of resolution with depth due to light scattering in biological tissue. Beyond a few millimeters in depth, diffuse transport dominates and makes high resolution imaging impossible using conventional techniques. In this work, light sheet imaging using x-ray photons was developed with a keV x-ray source. This partially overcomes this scattering by generating light within tissue at depth. The light excites fluorescent probes that can be used for tumor tracking based upon molecular targeting. Most of the fluorescent probes have a lifetime in the nanosecond range. In this study, the use of a portable linear accelerator delivering 30-ns x-ray pulses was explored. Using x-ray excitable fluorophores, light was generated within a tissue phantom. Image stacks were acquired using an intensified camera (PiMAX4 – Princeton Instrument – USA) placed perpendicularly to the slicing direction of the sample. A solid-state silicon photomultiplier was used to gate acquisition. Although this delayed acquisition slightly, it improved the fluorescence signal-to-noise ratio (SNR). A deconvolution algorithm counteracted the blurring effects of tissue, and image stacks were converted to 3D reconstructions. In summary, nanosecond x-ray pulses can be used to excite fluorophores through radioluminescence phenomenon. Combined with slice imaging, this approach shows promise for time-resolved x-ray luminescence.

Cherenkov light emission from tissue undergoing radiation therapy is a complex function of the dose deposition and is reduced by the optical attenuation of the tissue. A diffusion theory based integral of the remitted light is presented, using the assumption that only Cherenkov photons from the first 8 mm of tissue are able to appreciably escape from the surface. This depth restriction falls within the linear build-up region for both electron and photon beams used in radiotherapy. The resulting expression for Cherenkov light fluence formulated here indicates that the outgoing intensity is dependent upon the quasi-linear dose build up gradient (k₂) in the first 8 mm of tissue, is inversely proportional to the optical absorption (μ_a), and is relatively independent of the scattering coefficient (μ_s ^/ ). Numerical evaluation suggests that the diffuse component of Cherenkov light emission dominates over any unscattered photons, suggesting that the radiation build-up factor dominates what is imaged off the surface. This observation could allow for linear corrections to Cherenkov images with knowledge of tissue optical properties and for better interpretation of the origin of Cherenkov from tissue.

Fiber optic-based dosimeters composed of a scintillating sensor element connected to an un-doped transport optical fiber are interesting tools for radiation therapy dosimetry and quality assurance, due to their advantageous features including small physical size, mechanical flexibility, and being tissue-equivalent. With the introduction of emerging treatment modalities, especially with MRI-guidance available during radiation therapy, there is a need to fully investigate the influence of the magnetic field on the response of fiber optic dosimeters. In this work, we studied the Cherenkov light collected by transport optical fibers, manifested as a “stem effect” in fiber optic dosimeters. Two plastic fibers (core diameters of 1 and 2 mm) were irradiated with 6 MV photon beam generated using a conventional medical linear accelerator (no magnetic field) and an MRI-equipped linear accelerator with a 0.35 T magnetic field. The measurement setup was identical in both systems and the fibers received same amount of radiation dose. The fiber was placed between tissue-mimicking plastic layers at different depths and irradiated at a 10×10 cm² field size. Spectroscopy was performed using a fiber-coupled spectrometer in 450 to 650 nm range with 2.5 nm resolution. We found that the amount of Cherenkov light collected by the fibers is increased in the presence of the magnetic field. The amount of this increase depends on the fiber’s core size and depth of measurement.

X-ray luminescence imaging emerged for about a decade and combines both the high spatial resolution of x-ray imaging with the high measurement sensitivity of optical imaging, which could result in a great molecular imaging tool for small animals. So far, there are two types of x-ray luminescence computed tomography (XLCT) imaging. One uses a pencil beam x-ray for high spatial resolution at a cost of longer measurement time. The other uses cone beam x-ray to cover the whole mouse to obtain XLCT images at a very short time but with a compromised spatial resolution. Here we review these two methods in this paper and highlight the synthesized nanophosphors by different research groups.

We are building a focused x-ray luminescence tomography (FXLT) imaging system, developing a machinelearning based FXLT reconstruction algorithm, and synthesizing nanophosphors with different emission wavelengths. In this paper, we will report our current progress from these three aspects. Briefly, we mount all main components, including the focused x-ray tube, the fiber detector, and the x-ray tube and x-ray detector for a microCT system, on a rotary which is a heavy-duty ring track. A microCT scan will be performed before FXLT scan. For a FXLT scan, we will have four PMTs to measure four fiber detectors at two different wavelengths simultaneously for each linear scan position. We expect the spatial resolution of the FXLT imaging will be around 100 micrometers and a limit of detection of approximately 2 μg/mL (for Gd₂O₂S:Eu).

A spare reconstruction algorithm for Cherenkov-excited luminescence scanned tomography (CELST) is developed to improve quantitative accuracy when luminescent probes locate in deeper tissue. The proposed algorithm incorporates the sparse a priori information of probes into the reconstruction. A fast iterative shrinkage threshold algorithm (FISTA) and 3D block matching (BM3D) algorithm are jointly employed to recover the distribution of luminescent. Numerical simulations demonstrate that the proposed method can result in more accurate quantitative reconstruction and increase depth of detection as compared with conventional Tikhonov based reconstruction algorithm used in CELST.

Radiochromic polymer film dosimeters are strong candidates for radiation therapy dosimetry due to high spatial resolution, tissue-equivalency, relative ease of use, and the ability to provide two-dimensional measurement. In this work, we studied the growth kinetics of optical density of EBT3 and EBT-XD radiochromic film models, irradiated using megavoltage photon and proton therapy beams, over a period of 5 min to 120 hours post-irradiation.

Osteosarcoma is the most common primary malignant bone tumor in children. Patient survival with osteosarcoma is heavily influenced by the response to chemotherapy, measured by tumor necrosis upon histological analysis. Unfortunately, response is not measurable until the time of surgery and therefore modifications to chemotherapy protocol are only made after several weeks of treatment and surgery. Osteosarcoma tumors often demonstrate increased mineralization following the onset of chemotherapy. Furthermore, it has been hypothesized that this mineralization—apparent on radiographs—may correlate with chemotherapy response, however, this has not been demonstrated with qualitative visual evaluation. The ability to non-invasively measure a patient’s response to chemotherapy using plain radiographs, which is currently included in the normal clinical workflow, would guide the medical oncologists to tailor treatment for patients with osteosarcoma. After obtaining appropriate multi-center institutional review board approvals, we identified 31 patients that possess a pair of pre- and post-chemotherapy radiograph along with the necrosis measure. The images were digitized scans of physical radiographs between 1999 and 2013. Software was designed to measure the signal intensities in the tumor, a region of the soft tissue, air, and healthy bone. The tumor signals were normalized based on the random combination of air, soft tissue or bone, by subtraction or division. The differences in tumor signal between pre- and post-image were plotted against the percent necrosis determined by histological analysis. Different combinations of the normalization methods were compared based on the slope, coefficient of determination (R²) and Pearson correlation coefficient (ρ).