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Quantifying parenchymal tissue changes in the lungs is imperative in furthering the study of radiation induced lung damage (RILD). Registering lung images from different time-points is a key step of this process. Traditional intensity-based registration approaches fail this task due to the considerable anatomical changes that occur between timepoints. This work proposes a novel method to successfully register longitudinal pre- and post-radiotherapy (RT) lung computed tomography (CT) scans that exhibit large changes due to RILD, by extracting consistent anatomical features from CT (lung boundaries, main airways, vessels) and using these features to optimise the registrations. Pre-RT and 12 month post-RT CT pairs from fifteen lung cancer patients were used for this study, all with varying degrees of RILD, ranging from mild parenchymal change to extensive consolidation and collapse. For each CT, signed distance transforms from segmentations of the lungs and main airways were generated, and the Frangi vesselness map was calculated. These were concatenated into multi-channel images and diffeomorphic multichannel registration was performed for each image pair using NiftyReg. Traditional intensity-based registrations were also performed for comparison purposes. For the evaluation, the pre- and post-registration landmark distance was calculated for all patients, using an average of 44 manually identified landmark pairs per patient. The mean (standard deviation) distance for all datasets decreased from 15.95 (8.09) mm pre-registration to 4.56 (5.70) mm post-registration, compared to 7.90 (8.97) mm for the intensity-based registrations. Qualitative improvements in image alignment were observed for all patient datasets. For four representative subjects, registrations were performed for three additional follow-up timepoints up to 48 months post-RT and similar accuracy was achieved. We have demonstrated that our novel multichannel registration method can successfully align longitudinal scans from RILD patients in the presence of large anatomical changes such as consolidation and atelectasis, outperforming the traditional registration approach both quantitatively and through thorough visual inspection.

Reducing radiation-induced side effects is one of the most important challenges in paediatric cancer treatment. Recently, there has been growing interest in using spatial normalisation to enable voxel-based analysis of radiation-induced toxicities in a variety of patient groups. The need to consider three-dimensional distribution of doses, rather than dose-volume histograms, is desirable but not yet explored in paediatric populations. In this paper, we investigate the feasibility of atlas construction and spatial normalisation in paediatric radiotherapy. We used planning computed tomography (CT) scans from twenty paediatric patients historically treated with craniospinal irradiation to generate a template CT that is suitable for spatial normalisation. This childhood cancer population representative template was constructed using groupwise image registration. An independent set of 53 subjects from a variety of childhood malignancies was then used to assess the quality of the propagation of new subjects to this common reference space using deformable image registration (i.e. spatial normalisation). The method was evaluated in terms of overall image similarity metrics, contour similarity and preservation of dose-volume properties. After spatial normalisation, we report a dice similarity coefficient of 0.95 ± 0.05, 0.85 ± 0.04, 0.96 ± 0.01, 0.91 ± 0.03, 0.83 ± 0.06 and 0.65 ± 0.16 for brain and spinal canal, ocular globes, lungs, liver, kidneys and bladder. We then demonstrated the potential advantages of an atlas-based approach to study the risk of second malignant neoplasms after radiotherapy. Our findings indicate satisfactory mapping between a heterogeneous group of patients and the template CT. The poorest performance was for organs in the abdominal and pelvic region, likely due to respiratory and physiological motion and to the highly deformable nature of abdominal organs. More specialised algorithms should be explored in the future to improve mapping in these regions. This study is the first step toward voxel-based analysis in radiation-induced toxicities following paediatric radiotherapy.

Significance: The necessity to use exogenous probes for optical oxygen measurements in radiotherapy poses challenges for clinical applications. Options for implantable probe biotechnology need to be improved to alleviate toxicity concerns in human use and facilitate translation to clinical trial use. Aim: To develop an implantable oxygen sensor containing a phosphorescent oxygen probe such that the overall administered dose of the probe would be below the Federal Drug Administration (FDA)-prescribed microdose level, and the sensor would provide local high-intensity signal for longitudinal measurements of tissue pO2. Approach: PtG4, an oxygen quenched dendritic molecule, was mixed into an agarose matrix at 100 μM concentration, allowing for local injection into tumors at the total dose of 10 nmol per animal, forming a gel at the site of injection. Cherenkov-excited luminescence imaging (CELI) was used to acquire the phosphorescence and provide intratumoral pO2. Results: Although PtG4 does not form covalent bonds with agarose and gradually leaches out into the surrounding tissue, its retention time within the gel was sufficiently long to demonstrate the capability to measure intratumoral pO2 with the implantable gel sensors. The sensor’s performance was first evaluated in vitro in tissue simulation phantoms, and then the sensor was used to measure changes in oxygen in MDA-MB-231 tumors during hypofractionated radiotherapy. Conclusions: Our study demonstrates that implantable oxygen sensors in combination with CELI present a promising approach for quantifying oxygen changes during the course of radiation therapy and thus for evaluating the tumor response to radiation. By improving the design of the gel–probe composition in order to prevent leaching of the probe into the tissue, biosensors can be created that should allow longitudinal oxygen measurements in tumors by means of CELI while using FDA-compliant microdose levels of the probe and thus lowering toxicity concerns.

Significance: Due to patients’ respiratory movement or involuntary body movements during breast cancer radiotherapy, the mismatched adjacent fields in surface exposure regions could result in insufficient dosage or overdose in these regions, which would lead to tissue injury, excessive skin burns, and potential death. Cherenkov luminescence imaging (CLI) could be used to effectively detect the matching information of adjacent radiation fields without extra radiation or invasive imaging. Aim: Our objective was to provide a biological experimental basis for monitoring matching of adjacent radiation fields between photon and electron fields due to introduced shifts during radiotherapy by CLI technique. Approach: A medical accelerator was used to generate photon and electron fields. An industrial camera system was adopted to image the excited CLI signal during irradiation of chicken tissue with yellow (group A and group C experiments) or black color (group B experiment). The following introduced shifts were tested: 10, 5, 2, and 0 mm toward superior or inferior direction. A model was introduced to deal with matching error analysis of adjacent radiation fields due to introduced shifts with adapted plans used to treat neoplasms of the right breast with supraclavicular nodes or internal mammary lymph node. Results: The matching values between photon and electron fields were consistent with the tested introduced shifts during yellow chicken irradiation. In group A, average discrepancies were 0.59 ± 0.35 mm and 0.68 ± 0.37 mm for photon fields and electron fields in anterior/posterior (AP) direction, with 87% and 75% of measurement within 1 mm, respectively. In group C, average discrepancies were 0.80 ± 0.65 mm and 1.07 ± 0.57 mm for oblique photon field with gantry angles of 330 deg and 150 deg, with 66% and 65% of measurement within 1 mm, respectively. The average discrepancies were 0.44 ± 0.30 mm for electron field in the AP direction, with 94% of measurement within 1 mm. The matching error introduced by the proposed method was less than 1.5 mm for AP fields and 2 mm for oblique incidence fields. However, the field matching could not be monitored with black chicken tissue irradiation due to a weak CLI signal that could hardly be extracted from background noise in group B. Conclusions: CLI is demonstrated for the quantitative monitoring of the field match line on light biological tissue phantoms and has potential for monitoring of field matching in surface tissue during breast cancer radiotherapy.

Radiotherapy treatment planning for use with high-energy photon beams currently employs a binary approach in defining the planning target volume (PTV). We propose a margin concept that takes the beam directions into account, generating beam-dependent PTVs (bdPTVs) on a beam-by-beam basis. The resulting degree of overlaps between the bdPTVs are used within the optimisation process; the optimiser effectively considers the same voxel to be both target and organ at risk (OAR) with fractional contributions. We investigate the impact of this novel approach when applied to prostate radiotherapy treatments, and compare treatment plans generated using beam dependent margins to conventional margins. Five prostate patients were used in this planning study, and plans using beam dependent margins improved the sparing of high doses to target-surrounding OARs, though a trade-off in delivering additional low dose to the OARs can be observed. Plans using beam dependent margins are observed to have a slightly reduced target coverage. Nevertheless, all plans are able to satisfy 90% population coverage with the target receiving at least 95% of the prescribed dose to \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$D_{98\%}$ \end{document}D98%.

Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Unfortunately, whilst the use of margins can increase the probability that sufficient dose is delivered to the CTV, it can also result in delivering high dose of radiation to surrounding organs at risk (OARs). We expand on our previous work on beam-dependent margins and propose a novel adaptive margin concept, where margins are moulded away from selected OARs for better OAR-high-dose sparing, whilst maintaining similar dose coverage probability to the CTV. This, however, comes at a cost of a larger irradiation volume, and thus can negatively impact other structures. We investigate the impact of the adaptive margin concept when applied to prostate radiotherapy treatments, and compare treatment plans generated using our beam-dependent margins without adaptation, with adaption from the rectum and with adaptation from both the rectum and bladder. Five prostate patients were used in this planning study. All plans achieved similar dose coverage probability, and were able to ensure at least 90% population coverage with the target receiving at least 95% of the prescribed dose to [Formula: see text]. We observed overall better high-dose sparing to OARs that were considered when using the adapted beam-dependent PTVs, with the degree of sparing dependent on both the number of OARs under consideration as well as the relative position between the CTV and the OARs.

Cherenkov emission induced by external beam radiation therapy from a clinical linear accelerator (LINAC) can be used to excite phosphors deep in biological tissues. As with all luminescence imaging, there is a desire to minimize the spectral overlap between the excitation light and emission wavelengths, here between the Cherenkov and the phosphor. Cherenkov excited short-wavelength infrared (SWIR, 1000 to 1700 nm) fluorescence imaging has been demonstrated for the first time, using long Stokes-shift fluorophore PdSe quantum dots (QD) with nanosecond lifetime and an optimized SWIR detection. The 1/λ2 intensity spectrum characteristic of Cherenkov emission leads to low overlap of this into the fluorescence spectrum of PdSe QDs in the SWIR range. Additionally, using a SWIR camera itself inherently ignores the stronger Cherenkov emission wavelengths dominant across the visible spectrum. The SWIR luminescence was shown to extend the depth sensitivity of Cherenkov imaging, which could be used for applications in radiotherapy sensing and imaging in human tissue with targeted molecular probes.

A commercial active breathing coordinator (ABC) device, employed to hold respiration at a specific level for a predefined duration, was successfully adapted for magnetic resonance imaging (MRI) use for the first time. Potential effects of the necessary modifications were assessed and taken into account. Automatic MR acquisition during ABC breath holding was achieved. The feasibility of MR-ABC thoracic and abdominal examinations together with the advantages of imaging in repeated ABC-controlled breath holds were demonstrated on healthy volunteers. Five lung cancer patients were imaged under MR-ABC, visually confirming the very good intra-session reproducibility of organ position in images acquired with the same patient positioning as used for computed tomography (CT). Using identical ABC settings, good MR-CT inter-modality registration was achieved. This demonstrates the value of ABC, since application of T1, T2 and diffusion weighted MR sequences provides a wider range of contrast mechanisms and additional diagnostic information compared to CT, thus improving radiotherapy treatment planning and assessment.