Specificity of translocator protein-targeted positron emission tomography in inflammatory joint disease.

OBJECTIVE: Expression of the translocator protein (TSPO) on inflammatory cells has facilitated imaging of synovitis with TSPO-targeted positron emission tomography (PET). We aimed to quantitatively assess the specificity of the second-generation TSPO PET radioligand, [11C]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study. METHODS: Three IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [11C]PBR28-PET scans before and after administration of 90 mg of oral emapunil (XBD-173), a TSPO ligand the same day. Radial arterial blood sampling was performed throughout the scan, and total radioactivity and radioactive metabolites were obtained. A semi-automated method was used to generate regions of interest. Standardized uptake value (SUV) and SUV ratio corrected for activity in bone and blood between 50 and 70 min (SUVr50-70 bone, SUVr50-70 blood, respectively) and PET volume of distribution (VT) of the radioligand were calculated. RESULTS: A mean [11C]PBR28 radioactivity of 378 (range 362-389) MBq was administered. A significant decrease (p < 0.05) in VT, SUVr50-70 bone and SUVr50-70 blood observed after oral emapunil confirmed the TSPO specificity of [11C]PBR28. A decrease in SUV was not observed in the post-block scan. CONCLUSION: [11C]PBR28 is TSPO-specific radioligand in IJD patients. Simplified PET protocols with static PET acquisition can be used in the management and evaluation of novel therapeutics that target TSPO overexpressing cells.

A new approach to modeling the microdosimetry of proton therapy beams.

INTRODUCTION: To revisit the formulation of the mean chord length in microdosimetry and replace it by the particle mean free path appropriate for modelings in radiobiology. METHODS: We perform a collision-by-collision followed by event-by-event Geant4 Monte Carlo simulation and calculate double-averaged stepping length, 〈〈l〉〉, for a range of target sizes from mm down to µm and depth in water. We consider 〈〈l〉〉 to represent the particle mean free path. RESULTS: We show that 〈〈l〉〉 continuously drops as a function of depth and asymptotically saturates to a minimum value in low energies, where it exhibits a universal scaling behavior, independent of particle nominal beam energy. We correlate 〈〈l〉〉 to linear density of DNA damage, complexities of initial lethal lesions and illustrate a relative difference between predictive RBEs in model calculations using mean chord length vs the proposed mean free path. We demonstrate consistency between rapid increase in RBE within and beyond the Bragg peak and 〈〈l〉〉, a decreasing function of depth. DISCUSSION AND CONCLUSION: An interplay between localities in imparted energy at nanometer scale and subsequent physio-chemical processes, causalities and pathways in DNA damage requires substitution of geometrical chord length of cell nuclei by mean-free path of proton and charged particles to account for a mean distance among sequential collisions in DNA materials. To this end, the event averaging over cell volume in the current microdosimetry formalism must be superseded by the collision averaging scored within the volume. The former, is fundamentally a global attribute of the cell nuclei surfaces and boundaries and is characterized by their membrane diameters, hence such global indices are not appropriate to quantitatively represent the radiobiological strength of the particles and their RBE variabilities that is associated with the sensitivities to local structure of the collisions and their spatio-temporal collective patterns in DNA materials.

Integrin αvß6 Positron Emission Tomography Imaging in Lung Cancer Patients Treated With Pulmonary Radiation Therapy.

PURPOSE: Post radiation therapy (RT) lung fibrosis is a major barrier to improved cure rate in lung cancer. Integrin αvß6 plays a key role in fibrogenesis by activating transforming growth factor-ß. Positron emission tomography (PET) studies with a fluorine-18 radiolabelled αvß6 radioligand, [18F]-FBA-A20FMDV2, were performed to assess uptake, and the relationship to RT dose parameters was explored. METHODS AND MATERIALS: Recently treated non-small cell lung cancer patients (<6 months after RT) had [18F]-FBA-A20FMDV2-PET scans, coregistered with the RT planning computed tomography and segmented to RT doses of >40 Gy (excluding tumor), 25 to 40 Gy, 15 to 25 Gy, 8 to 15 Gy, and <8 Gy. PET uptake (standardized uptake value; SUV) corrected for tissue density between 10 and 60 minutes (SUV10-60) was calculated and compared with RT dose, dose per fraction, and biological effective dose (BED). PET uptake was also evaluated in healthy volunteers. RESULTS: Six non-small cell lung cancer (3 male; 3 female) subjects scanned between 6 and 22 weeks after RT and 6 healthy volunteers (3 males; 3 females) were evaluated. Higher mean PET uptake (SUV10-60) was observed in the irradiated lung compared with the healthy lung (2.97 vs 1.99; P < .05). A significant and positive pharmacodynamic relationship was observed between radioligand uptake (SUV10-60) and dose per RT fraction (r2 = 0.63; P < .001) and with BED for fibrosis (r2 = 0.38; P < .001 for α/ß 3 Gy and r2 = 0.33; P < 0.001 for α/ß 5 Gy). CONCLUSIONS: Higher uptake in the irradiated lung and a pharmacodynamic relationship between αvß6 radioligand uptake versus RT dose per fraction and BED for lung fibrosis is consistent with RT induced activation of αvß6 integrin and supports a role for αvß6 in the induction of lung fibrosis after pulmonary RT. αvß6-PET imaging may potentially aid in the assessment and management of radiation-induced pulmonary fibrosis.

Quality assurance in proton beam therapy using a plastic scintillator and a commercially available digital camera.

PURPOSE: In this article, we evaluate a plastic scintillation detector system for quality assurance in proton therapy using a BC-408 plastic scintillator, a commercial camera, and a computer. METHODS: The basic characteristics of the system were assessed in a series of proton irradiations. The reproducibility and response to changes of dose, dose-rate, and proton energy were determined. Photographs of the scintillation light distributions were acquired, and compared with Geant4 Monte Carlo simulations and with depth-dose curves measured with an ionization chamber. A quenching effect was observed at the Bragg peak of the 60 MeV proton beam where less light was produced than expected. We developed an approach using Birks equation to correct for this quenching. We simulated the linear energy transfer (LET) as a function of depth in Geant4 and found Birks constant by comparing the calculated LET and measured scintillation light distribution. We then used the derived value of Birks constant to correct the measured scintillation light distribution for quenching using Geant4. RESULTS: The corrected light output from the scintillator increased linearly with dose. The system is stable and offers short-term reproducibility to within 0.80%. No dose rate dependency was observed in this work. CONCLUSIONS: This approach offers an effective way to correct for quenching, and could provide a method for rapid, convenient, routine quality assurance for clinical proton beams. Furthermore, the system has the advantage of providing 2D visualization of individual radiation fields, with potential application for quality assurance of complex, time-varying fields.

Bayesian Estimation of Intrinsic Tissue Oxygenation and Perfusion From RGB Images.

Multispectral imaging (MSI) can potentially assist the intra-operative assessment of tissue structure, function and viability, by providing information about oxygenation. In this paper, we present a novel technique for recovering intrinsic MSI measurements from endoscopic RGB images without custom hardware adaptations. The advantage of this approach is that it requires no modification to existing surgical and diagnostic endoscopic imaging systems. Our method uses a radiometric color calibration of the endoscopic camera's sensor in conjunction with a Bayesian framework to recover a per-pixel measurement of the total blood volume (THb) and oxygen saturation (SO2) in the observed tissue. The sensor's pixel measurements are modeled as weighted sums over a mixture of Poisson distributions and we optimize the variables SO2 and THb to maximize the likelihood of the observations. To validate our technique, we use synthetic images generated from Monte Carlo physics simulation of light transport through soft tissue containing sub-surface blood vessels. We also validate our method on in vivo data by comparing it to a MSI dataset acquired with a hardware system that sequentially images multiple spectral bands without overlap. Our results are promising and show that we are able to provide surgeons with additional relevant information by processing endoscopic images with our modeling and inference framework.

Imaging Cerenkov emission as a quality assurance tool in electron radiotherapy.

A new potential quality assurance (QA) method is explored (including assessment of depth dose, dose linearity, dose rate linearity and beam profile) for clinical electron beams based on imaging Cerenkov light. The potential of using a standard commercial camera to image Cerenkov light generated from electrons in water for fast QA measurement of a clinical electron beam was explored and compared to ionization chamber measurements. The new method was found to be linear with dose and independent of dose rate (to within 3%). The uncorrected practical range measured in Cerenkov images was found to overestimate the actual value by 3 mm in the worst case. The field size measurements underestimated the dose at the edges by 5% without applying any correction factor. Still, the measured field size could be used to monitor relative changes in the beam profile. Finally, the beam-direction profile measurements were independent of the field size within 2%. A simulation was also performed of the deposited energy and of Cerenkov production in water using GEANT4. Monte Carlo simulation was used to predict the measured light distribution around the water phantom, to reproduce Cerenkov images and to find the relation between deposited energy and Cerenkov production. The camera was modelled as a pinhole camera in GEANT4, to attempt to reproduce Cerenkov images. Simulations of the deposited energy and the Cerenkov light production agreed with each other for a pencil beam of electrons, while for a realistic field size, Cerenkov production in the build-up region overestimated the dose by +8%.