RESUMEN

Objective.To investigate the potential of 3D-printable thermoplastics as tissue-equivalent materials to be used in multimodal radiotherapy end-to-end quality assurance (QA) devices.Approach.Six thermoplastics were investigated: Polylactic Acid (PLA), Acrylonitrile Butadiene Styrene (ABS), Polyethylene Terephthalate Glycol (PETG), Polymethyl Methacrylate (PMMA), High Impact Polystyrene (HIPS) and StoneFil. Measurements of mass density (ρ), Relative Electron Density (RED), in a nominal 6 MV photon beam, and Relative Stopping Power (RSP), in a 210 MeV proton pencil-beam, were performed. Average Hounsfield Units (HU) were derived from CTs acquired with two independent scanners. The calibration curves of both scanners were used to predict averageρ,RED and RSP values and compared against the experimental data. Finally, measured data ofρ,RED and RSP was compared against theoretical values estimated for the thermoplastic materials and biological tissues.Main results.Overall, goodρand RSP CT predictions were made; only PMMA and PETG showed differences >5%. The differences between experimental and CT predicted RED values were also <5% for PLA, ABS, PETG and PMMA; for HIPS and StoneFil higher differences were found (6.94% and 9.42/15.34%, respectively). Small HU variations were obtained in the CTs for all materials indicating good uniform density distribution in the samples production. ABS, PLA, PETG and PMMA showed potential equivalency for a variety of soft tissues (adipose tissue, skeletal muscle, brain and lung tissues, differences within 0.19%-8.35% for all properties). StoneFil was the closest substitute to bone, but differences were >10%. Theoretical calculations of all properties agreed with experimental values within 5% difference for most thermoplastics.Significance.Several 3D-printed thermoplastics were promising tissue-equivalent materials to be used in devices for end-to-end multimodal radiotherapy QA and may not require corrections in treatment planning systems' dose calculations. Theoretical calculations showed promise in identifying thermoplastics matching target biological tissues before experiments are performed.

Asunto(s)

Fotones , Polimetil Metacrilato , Impresión Tridimensional , Terapia de Protones , Humanos , Terapia de Protones/métodos , Terapia de Protones/instrumentación , Polimetil Metacrilato/química , Poliésteres/química , Plásticos , Poliestirenos/química , Calibración , Garantía de la Calidad de Atención de Salud , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica , Ensayo de Materiales , Resinas Acrílicas , Butadienos

RESUMEN

Here, we report on the process of a highly impactful and successful creative, collaborative, and multi-partner public engagement project, Radiation Reveal. It brought together ten young adults aged 17-25-year-olds with experience of radiotherapy with researchers at Cancer Research UK RadNet City of London across three 2-hour online workshops. Our aims were to 1) initiate discussions between young adults and radiation researchers, and 2) identify what people wish they had known about radiotherapy before or during treatment. These aims were surpassed; other benefits included peer support, participants' continued involvement in subsequent engagement projects, lasting friendships, creation of support groups for others, and creation and national dissemination of top ten tips for medical professionals and social media resources. A key learning was that this project required a dedicated and (com)passionate person with connections to national cancer charities. When designing the project, constant feedback is also needed from charities and young adults with and without radiotherapy experience. Finally, visually capturing discussions and keeping the door open beyond workshops further enhanced impact. Here, we hope to inform and inspire people to help project the patient voice in all we do.

Asunto(s)

Neoplasias , Humanos , Adulto Joven , Adulto , Adolescente , Femenino , Masculino , Neoplasias/radioterapia , Investigación Biomédica

RESUMEN

This study aimed to validate a bespoke 3D-printed phantom for use in quality assurance (QA) of a 6 degrees-of-freedom (6DoF) treatment couch. A novel phantom design comprising a main body with internal cube structures, was fabricated at five centres using Polylactic Acid (PLA) material, with an additional phantom produced incorporating a PLA-stone hybrid material. Correctional setup shifts were determined using image registration by 3D-3D matching of high HU cube structures between obtained cone-beam computer tomography (CBCT) images to reference CTs, containing cubes with fabricated rotational offsets of 3.5°, 1.5° and -2.5° in rotation, pitch, and roll, respectively. Average rotational setup shifts were obtained for each phantom. The reproducibility of 3D-printing was probed by comparing the internal cube size as well as Hounsfield Units between each of the uniquely produced phantoms. For the five PLA phantoms, the average rot, pitch and roll correctional differences from the fabricated offsets were -0.3 ± 0.2°, -0.2 ± 0.5° and 0.2 ± 0.3° respectively, and for the PLA hybrid these differences were -0.09 ± 0.14°, 0.30 ± 0.00° and 0.03 ± 0.10°. There was found to be no statistically significant difference in average cube size between the five PLA printed phantoms, with the significant difference (P < 0.05) in HU of one phantom compared to the others attributed to setup choice and material density. This work demonstrated the capability producing a novel 3D-printed 6DoF couch QA phantom design, at multiple centres, with each unique model capable of sub-degree couch correction.

Asunto(s)

Radiocirugia , Radioterapia Guiada por Imagen , Reproducibilidad de los Resultados , Radiocirugia/métodos , Fantasmas de Imagen , Impresión Tridimensional , Poliésteres

RESUMEN

OBJECTIVES: To identify variables predicting interfractional anatomical variations measured with cone-beam CT (CBCT) throughout abdominal paediatric radiotherapy, and to assess the potential of surface-guided radiotherapy (SGRT) to monitor these changes. METHODS: Metrics of variation in gastrointestinal (GI) gas volume and separation of the body contour and abdominal wall were calculated from 21 planning CTs and 77 weekly CBCTs for 21 abdominal neuroblastoma patients (median 4 years, range: 2 - 19 years). Age, sex, feeding tubes, and general anaesthesia (GA) were explored as predictive variables for anatomical variation. Furthermore, GI gas variation was correlated with changes in body and abdominal wall separation, as well as simulated SGRT metrics of translational and rotational corrections between CT/CBCT. RESULTS: GI gas volumes varied 74 ± 54 ml across all scans, while body and abdominal wall separation varied 2.0 ± 0.7 mm and 4.1 ± 1.5 mm from planning, respectively. Patients < 3.5 years (p = 0.04) and treated under GA (p < 0.01) experienced greater GI gas variation; GA was the strongest predictor in multivariate analysis (p < 0.01). Absence of feeding tubes was linked to greater body contour variation (p = 0.03). GI gas variation correlated with body (R = 0.53) and abdominal wall (R = 0.63) changes. The strongest correlations with SGRT metrics were found for anterior-posterior translation (R = 0.65) and rotation of the left-right axis (R = -0.36). CONCLUSIONS: Young age, GA, and absence of feeding tubes were linked to stronger interfractional anatomical variation and are likely indicative of patients benefiting from adaptive/robust planning pathways. Our data suggest a role for SGRT to inform the need for CBCT at each treatment fraction in this patient group. ADVANCES IN KNOWLEDGE: This is the first study to suggest the potential role of SGRT for the management of internal interfractional anatomical variation in paediatric abdominal radiotherapy.

Asunto(s)

Radioterapia Guiada por Imagen , Humanos , Niño , Radioterapia Guiada por Imagen/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Abdomen/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos

RESUMEN

Objective. Adaptive radiotherapy workflows require images with the quality of computed tomography (CT) for re-calculation and re-optimisation of radiation doses. In this work we aim to improve the quality of on-board cone beam CT (CBCT) images for dose calculation using deep learning.Approach. We propose a novel framework for CBCT-to-CT synthesis using cycle-consistent Generative Adversarial Networks (cycleGANs). The framework was tailored for paediatric abdominal patients, a challenging application due to the inter-fractional variability in bowel filling and small patient numbers. We introduced to the networks the concept of global residuals only learning and modified the cycleGAN loss function to explicitly promote structural consistency between source and synthetic images. Finally, to compensate for the anatomical variability and address the difficulties in collecting large datasets in the paediatric population, we applied a smart 2D slice selection based on the common field-of-view (abdomen) to our imaging dataset. This acted as a weakly paired data approach that allowed us to take advantage of scans from patients treated for a variety of malignancies (thoracic-abdominal-pelvic) for training purposes. We first optimised the proposed framework and benchmarked its performance on a development dataset. Later, a comprehensive quantitative evaluation was performed on an unseen dataset, which included calculating global image similarity metrics, segmentation-based measures and proton therapy-specific metrics.Main results. We found improved performance for our proposed method, compared to a baseline cycleGAN implementation, on image-similarity metrics such as Mean Absolute Error calculated for a matched virtual CT (55.0 ± 16.6 HU proposed versus 58.9 ± 16.8 HU baseline). There was also a higher level of structural agreement for gastrointestinal gas between source and synthetic images measured using the dice similarity coefficient (0.872 ± 0.053 proposed versus 0.846 ± 0.052 baseline). Differences found in water-equivalent thickness metrics were also smaller for our method (3.3 ± 2.4% proposed versus 3.7 ± 2.8% baseline).Significance. Our findings indicate that our innovations to the cycleGAN framework improved the quality and structure consistency of the synthetic CTs generated.

Asunto(s)

Aprendizaje Profundo , Humanos , Niño , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Rayos X , Tomografía Computarizada de Haz Cónico/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Abdomen

RESUMEN

Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as 'acceptable', 'minor disagreement' or 'major disagreement'. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.

RESUMEN

We present a novel classification system of the parenchymal features of radiation-induced lung damage (RILD). We developed a deep learning network to automate the delineation of five classes of parenchymal textures. We quantify the volumetric change in classes after radiotherapy in order to allow detailed, quantitative descriptions of the evolution of lung parenchyma up to 24 months after RT, and correlate these with radiotherapy dose and respiratory outcomes. Diagnostic CTs were available pre-RT, and at 3, 6, 12 and 24 months post-RT, for 46 subjects enrolled in a clinical trial of chemoradiotherapy for non-small cell lung cancer. All 230 CT scans were segmented using our network. The five parenchymal classes showed distinct temporal patterns. Moderate correlation was seen between change in tissue class volume and clinical and dosimetric parameters, e.g., the Pearson correlation coefficient was ≤0.49 between V30 and change in Class 2, and was 0.39 between change in Class 1 and decline in FVC. The effect of the local dose on tissue class revealed a strong dose-dependent relationship. Respiratory function measured by spirometry and MRC dyspnoea scores after radiotherapy correlated with the measured radiological RILD. We demonstrate the potential of using our approach to analyse and understand the morphological and functional evolution of RILD in greater detail than previously possible.

RESUMEN

BACKGROUND AND PURPOSE: State-of-the-art radiotherapy modalities have the potential of reducing late effects of treatment in childhood cancer survivors. Our aim was to investigate the carcinogenic risk associated with 3D conformal (photon) radiation (3D-CRT), intensity modulated arc therapy (IMAT) and pencil beam scanning proton therapy (PBS-PT) in the treatment of paediatric abdominal neuroblastoma. MATERIALS AND METHODS: The risk of radiation-induced second malignant neoplasm (SMN) was estimated using the concept of organ equivalent dose (OED) for eleven organs (lungs, rectum, colon, stomach, small intestine, liver, bladder, skin, central nervous system (CNS), bone, and soft tissues). The risk ratio (RR) between radiotherapy modalities and lifetime absolute risks (LAR) were reported for twenty abdominal neuroblastoma patients (median, 4y; range, 1-9y) historically treated with 3D-CRT that were also retrospectively replanned for IMAT and PBS-PT. RESULTS: The risk of SMN due to primary radiation was reduced in PBS-PT against 3D-CRT and IMAT for most patients and organs. The RR across all organs ranged from 0.38 ± 0.22 (bladder) to 0.98 ± 0.04 (CNS) between PBS-PT and IMAT, and 0.12 ± 0.06 (rectum and bladder) to 1.06 ± 0.43 (bone) between PBS-PT and 3D-CRT. The LAR for most organs was within 0.01-1% (except the colon) with a cumulative risk of 21 ± 13%, 35 ± 14% and 35 ± 16% for PBS-PT, IMAT and 3D-CRT, respectively. CONCLUSIONS: PBS-PT was associated with the lowest risk of radiation-induced SMN compared to IMAT and 3D-CRT in abdominal neuroblastoma treatment. Other clinical endpoints and plan robustness should also be considered for optimal plan selection.

RESUMEN

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.

Asunto(s)

Neoplasias , Planificación de la Radioterapia Asistida por Computador , Algoritmos , Niño , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Pelvis , Tomografía Computarizada por Rayos X

RESUMEN

BACKGROUND AND PURPOSE: Radiation-induced lung damage (RILD) is a common consequence of lung cancer radiotherapy (RT) with unclear evolution over time. We quantify radiological RILD longitudinally and correlate it with dosimetry and respiratory morbidity. MATERIALS AND METHODS: CTs were available pre-RT and at 3, 6, 12 and 24-months post-RT for forty-five subjects enrolled in a phase 1/2 clinical trial of isotoxic, dose-escalated chemoradiotherapy for locally advanced non-small cell lung cancer. Fifteen CT-based measures of parenchymal, pleural and lung volume change, and anatomical distortions, were calculated. Respiratory morbidity was assessed with the Medical Research Council (MRC) dyspnoea score and spirometric pulmonary function tests (PFTs): FVC, FEV1, FEV1/FVC and DLCO. RESULTS: FEV1, FEV1/FVC and MRC scores progressively declined post-RT; FVC decreased by 6-months before partially recovering. Radiologically, an early phase (3-6 months) of acute inflammation was characterised by reversible parenchymal change and non-progressive anatomical distortion. A phase of chronic scarring followed (6-24 months) with irreversible parenchymal change, progressive volume loss and anatomical distortion. Post-RT increase in contralateral lung volume was common. Normal lung volume shrinkage correlated longitudinally with mean lung dose (r = 0.30-0.40, p = 0.01-0.04). Radiological findings allowed separation of patients with predominant acute versus chronic RILD; subjects with predominantly chronic RILD had poorer pre-RT lung function. CONCLUSIONS: CT-based measures enable detailed quantification of the longitudinal evolution of RILD. The majority of patients developed progressive lung damage, even when the early phase was absent or mild. Pre-RT lung function and RT dosimetry may allow to identify subjects at increased risk of RILD.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X

RESUMEN

Aim: Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as magnetic resonance imaging (MRI) contrast agents; however, a number of T2-weighted imaging SPIONs have been withdrawn due to their poor clinical contrast performance. Our aim was to significantly improve SPION T2-weighted MRI contrast by clustering SPIONs within novel chitosan amphiphiles. Methods: Clustering SPIONs was achieved by encapsulation of hydrophobic-coated SPIONs with an amphiphilic chitosan polymer (GCPQ). Results: Clustering increases the spin-spin (r2) to spin-lattice (r1) relaxation ratio (r2/r1) from 3.0 to 79.1, resulting in superior contrast. Intravenously administered clustered SPIONs accumulated only in the liver and spleen; with the reduction in T2 relaxation confined, in the liver, to the extravascular space, giving clear MRI images of the liver vasculature.

Asunto(s)

Quitosano/química , Medios de Contraste/química , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Animales , Medios de Contraste/administración & dosificación , Interacciones Hidrofóbicas e Hidrofílicas , Hígado/irrigación sanguínea , Hígado/diagnóstico por imagen , Ratones Endogámicos BALB C , Micelas , Bazo/diagnóstico por imagen , Distribución Tisular

Asunto(s)

Pulmón , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Radiografía

RESUMEN

PURPOSE: Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long-term radiation-induced lung damage (RILD). However, there are still no objective criteria to quantify RILD, leading to variable reporting across centers and trials. We propose a set of objective imaging biomarkers for quantifying common radiologic findings observed 12 months after lung cancer radiation therapy. METHODS AND MATERIALS: Baseline and 12-month computed tomography (CT) scans of 27 patients from a phase 1/2 clinical trial of isotoxic chemoradiation were included in this study. To detect and measure the severity of RILD, 12 quantitative imaging biomarkers were developed. The biomarkers describe basic CT findings, including parenchymal change, volume reduction, and pleural change. The imaging biomarkers were implemented as semiautomated image analysis pipelines and were assessed against visual assessment of the occurrence of each change. RESULTS: Most of the biomarkers were measurable in each patient. The continuous nature of the biomarkers allows objective scoring of severity for each patient. For each imaging biomarker, the cohort was split into 2 groups according to the presence or absence of the biomarker by visual assessment, testing the hypothesis that the imaging biomarkers were different in the 2 groups. All features were statistically significant except for rotation of the main bronchus and diaphragmatic curvature. Most of the biomarkers were not strongly correlated with each other, suggesting that each of the biomarkers is measuring a separate element of RILD pathology. CONCLUSIONS: We developed objective CT-based imaging biomarkers that quantify the severity of radiologic lung damage after radiation therapy. These biomarkers are representative of typical radiologic findings of RILD.

Asunto(s)

Quimioradioterapia/efectos adversos , Neoplasias Pulmonares/terapia , Pulmón/efectos de la radiación , Traumatismos por Radiación/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

PURPOSE: To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. MATERIAL AND METHODS: Baseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. RESULTS: Six patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. CONCLUSIONS: Parenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic.

Asunto(s)

Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/efectos de la radiación , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patología , Tomografía Computarizada por Rayos X/métodos

RESUMEN

PURPOSE: An adaptive proton therapy workflow using cone beam computed tomography (CBCT) is proposed. It consists of an online evaluation of a fast range-corrected dose distribution based on a virtual CT (vCT) scan. This can be followed by more accurate offline dose recalculation on the vCT scan, which can trigger a rescan CT (rCT) for replanning. METHODS AND MATERIALS: The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the target's distal surface. RESULTS: The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology. CONCLUSIONS: A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.

Asunto(s)

Algoritmos , Tomografía Computarizada de Haz Cónico/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Terapia de Protones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Agua Corporal/diagnóstico por imagen , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/efectos de la radiación , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Estudios Retrospectivos

RESUMEN

Neuregulin (NRG) is an EGF-related growth factor that binds to the tyrosine kinase receptors ErbB3 and ErbB4, thus inducing tissue development and muscle glucose utilization during contraction. Here, we analyzed whether NRG has systemic effects regulating glycemia in control and type 2 diabetic rats. To this end, recombinant NRG (rNRG) was injected into Zucker diabetic fatty (ZDF) rats and their respective lean littermates 15 min before a glucose tolerance test (GTT) was performed. rNRG enhanced glucose tolerance without promoting the activation of the insulin receptor (IR) or insulin receptor substrates (IRS) in muscle and liver. However, in control rats, rNRG induced the phosphorylation of protein kinase B (PKB) and glycogen synthase kinase-3 (GSK-3) in liver but not in muscle. In liver, rNRG increased ErbB3 tyrosine phosphorylation and its binding to phosphatidylinositol 3-kinase (PI3K), thus indicating that rNRG activates the ErbB3/PI3K/PKB signaling pathway. rNRG increased glycogen content in liver but not in muscle. rNRG also increased the content of fructose-2,6-bisphosphate (Fru-2,6-P2), an activator of hepatic glycolysis, and lactate in liver but not in muscle. Increases in lactate were abrogated by wortmannin, a PI3K inhibitor, in incubated hepatocytes. The liver of ZDF rats showed a reduced content of ErbB3 receptors, entailing a minor stimulation of the rNRG-induced PKB/GSK-3 cascade and resulting in unaltered hepatic glycogen content. Nonetheless, rNRG increased hepatic Fru-2,6-P2 and augmented lactate both in liver and in plasma of diabetic rats. As a whole, rNRG improved response to the GTT in both control and diabetic rats by enhancing hepatic glucose utilization.

Asunto(s)

Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/metabolismo , Hígado/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Neurregulinas/farmacología , Animales , Glucemia/metabolismo , Estudios de Casos y Controles , Fructosadifosfatos/metabolismo , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Glucógeno Sintasa Quinasa 3/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Insulina , Proteínas Sustrato del Receptor de Insulina/efectos de los fármacos , Proteínas Sustrato del Receptor de Insulina/metabolismo , Ácido Láctico/metabolismo , Hígado/metabolismo , Glucógeno Hepático/metabolismo , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinasa/efectos de los fármacos , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Zucker , Receptor ErbB-3/efectos de los fármacos , Receptor ErbB-3/metabolismo , Receptor de Insulina/efectos de los fármacos , Receptor de Insulina/metabolismo

RESUMEN

PURPOSE: The aim of this study was to assess whether clinically acceptable segmentations of organs at risk (OARs) in head and neck cancer can be obtained automatically and efficiently using the novel "similarity and truth estimation for propagated segmentations" (STEPS) compared to the traditional "simultaneous truth and performance level estimation" (STAPLE) algorithm. METHODS: First, 6 OARs were contoured by 2 radiation oncologists in a dataset of 100 patients with head and neck cancer on planning computed tomography images. Each image in the dataset was then automatically segmented with STAPLE and STEPS using those manual contours. Dice similarity coefficient (DSC) was then used to compare the accuracy of these automatic methods. Second, in a blind experiment, three separate and distinct trained physicians graded manual and automatic segmentations into one of the following three grades: clinically acceptable as determined by universal delineation guidelines (grade A), reasonably acceptable for clinical practice upon manual editing (grade B), and not acceptable (grade C). Finally, STEPS segmentations graded B were selected and one of the physicians manually edited them to grade A. Editing time was recorded. RESULTS: Significant improvements in DSC can be seen when using the STEPS algorithm on large structures such as the brainstem, spinal canal, and left/right parotid compared to the STAPLE algorithm (all p < 0.001). In addition, across all three trained physicians, manual and STEPS segmentation grades were not significantly different for the brainstem, spinal canal, parotid (right/left), and optic chiasm (all p > 0.100). In contrast, STEPS segmentation grades were lower for the eyes (p < 0.001). Across all OARs and all physicians, STEPS produced segmentations graded as well as manual contouring at a rate of 83%, giving a lower bound on this rate of 80% with 95% confidence. Reduction in manual interaction time was on average 61% and 93% when automatic segmentations did and did not, respectively, require manual editing. CONCLUSIONS: The STEPS algorithm showed better performance than the STAPLE algorithm in segmenting OARs for radiotherapy of the head and neck. It can automatically produce clinically acceptable segmentation of OARs, with results as relevant as manual contouring for the brainstem, spinal canal, the parotids (left/right), and optic chiasm. A substantial reduction in manual labor was achieved when using STEPS even when manual editing was necessary.

Asunto(s)

Algoritmos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Órganos en Riesgo/efectos de la radiación , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada/efectos adversos , Tomografía Computarizada por Rayos X

RESUMEN

PURPOSE: The aims of this work were to evaluate the performance of several deformable image registration (DIR) algorithms implemented in our in-house software (NiftyReg) and the uncertainties inherent to using different algorithms for dose warping. METHODS: The authors describe a DIR based adaptive radiotherapy workflow, using CT and cone-beam CT (CBCT) imaging. The transformations that mapped the anatomy between the two time points were obtained using four different DIR approaches available in NiftyReg. These included a standard unidirectional algorithm and more sophisticated bidirectional ones that encourage or ensure inverse consistency. The forward (CT-to-CBCT) deformation vector fields (DVFs) were used to propagate the CT Hounsfield units and structures to the daily geometry for "dose of the day" calculations, while the backward (CBCT-to-CT) DVFs were used to remap the dose of the day onto the planning CT (pCT). Data from five head and neck patients were used to evaluate the performance of each implementation based on geometrical matching, physical properties of the DVFs, and similarity between warped dose distributions. Geometrical matching was verified in terms of dice similarity coefficient (DSC), distance transform, false positives, and false negatives. The physical properties of the DVFs were assessed calculating the harmonic energy, determinant of the Jacobian, and inverse consistency error of the transformations. Dose distributions were displayed on the pCT dose space and compared using dose difference (DD), distance to dose difference, and dose volume histograms. RESULTS: All the DIR algorithms gave similar results in terms of geometrical matching, with an average DSC of 0.85 ± 0.08, but the underlying properties of the DVFs varied in terms of smoothness and inverse consistency. When comparing the doses warped by different algorithms, we found a root mean square DD of 1.9% ± 0.8% of the prescribed dose (pD) and that an average of 9% ± 4% of voxels within the treated volume failed a 2%pD DD-test (DD2%-pp). Larger DD2%-pp was found within the high dose gradient (21% ± 6%) and regions where the CBCT quality was poorer (28% ± 9%). The differences when estimating the mean and maximum dose delivered to organs-at-risk were up to 2.0%pD and 2.8%pD, respectively. CONCLUSIONS: The authors evaluated several DIR algorithms for CT-to-CBCT registrations. In spite of all methods resulting in comparable geometrical matching, the choice of DIR implementation leads to uncertainties in dose warped, particularly in regions of high gradient and/or poor imaging quality.

Asunto(s)

Algoritmos , Neoplasias de Cabeza y Cuello/radioterapia , Procesamiento de Imagen Asistido por Computador/métodos , Dosis de Radiación , Radioterapia de Intensidad Modulada , Incertidumbre , Tomografía Computarizada de Haz Cónico , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador , Estudios Retrospectivos

RESUMEN

PURPOSE: The aim of this study was to evaluate the appropriateness of using computed tomography (CT) to cone-beam CT (CBCT) deformable image registration (DIR) for the application of calculating the "dose of the day" received by a head and neck patient. METHODS: NiftyReg is an open-source registration package implemented in our institution. The affine registration uses a Block Matching-based approach, while the deformable registration is a GPU implementation of the popular B-spline Free Form Deformation algorithm. Two independent tests were performed to assess the suitability of our registrations methodology for "dose of the day" calculations in a deformed CT. A geometric evaluation was performed to assess the ability of the DIR method to map identical structures between the CT and CBCT datasets. Features delineated in the planning CT were warped and compared with features manually drawn on the CBCT. The authors computed the dice similarity coefficient (DSC), distance transformation, and centre of mass distance between features. A dosimetric evaluation was performed to evaluate the clinical significance of the registrations errors in the application proposed and to identify the limitations of the approximations used. Dose calculations for the same intensity-modulated radiation therapy plan on the deformed CT and replan CT were compared. Dose distributions were compared in terms of dose differences (DD), gamma analysis, target coverage, and dose volume histograms (DVHs). Doses calculated in a rigidly aligned CT and directly in an extended CBCT were also evaluated. RESULTS: A mean value of 0.850 in DSC was achieved in overlap between manually delineated and warped features, with the distance between surfaces being less than 2 mm on over 90% of the pixels. Deformable registration was clearly superior to rigid registration in mapping identical structures between the two datasets. The dose recalculated in the deformed CT is a good match to the dose calculated on a replan CT. The DD is smaller than 2% of the prescribed dose on 90% of the body's voxels and it passes a 2% and 2 mm gamma-test on over 95% of the voxels. Target coverage similarity was assessed in terms of the 95%-isodose volumes. A mean value of 0.962 was obtained for the DSC, while the distance between surfaces is less than 2 mm in 95.4% of the pixels. The method proposed provided adequate dose estimation, closer to the gold standard than the other two approaches. Differences in DVH curves were mainly due to differences in the OARs definition (manual vs warped) and not due to differences in dose estimation (dose calculated in replan CT vs dose calculated in deformed CT). CONCLUSIONS: Deforming a planning CT to match a daily CBCT provides the tools needed for the calculation of the "dose of the day" without the need to acquire a new CT. The initial clinical application of our method will be weekly offline calculations of the "dose of the day," and use this information to inform adaptive radiotherapy (ART). The work here presented is a first step into a full implementation of a "dose-driven" online ART.

Asunto(s)

Tomografía Computarizada de Haz Cónico/métodos , Neoplasias de Cabeza y Cuello/radioterapia , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiometría/métodos , Radioterapia de Intensidad Modulada/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Algoritmos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programas Informáticos