Clinical implementation of a log file-based machine and patient QA system for IMRT and VMAT treatment plans.

PURPOSE: To determine the error detection sensitivity of a commercial log file-based system (LINACWatch®, LW) for integration into clinical routine and to compare it with a measurement device (OCTAVIUS 4D, Oct4D) for IMRT and VMAT delivery QA. MATERIALS AND METHODS: 76 VMAT/IMRT plans (H&N, prostate, rectum and breast) preliminarily classified according to their Modulation Complexity Score (MCS) calculated by LW, were considered. Receiver Operating Characteristic (ROC) Curves were used to establish gamma criteria for LW. 12 plans (3 for each site) were intentionally modified in order to introduce delivery errors regarding MLC, jaws, collimator, gantry and MU (for a total set of 168 incorrect plans) and irradiated on Oct4D; the corresponding log files were analysed by LW. Each incorrect plan was compared to the error-free plan using γ-index analysis for MLC, jaws and MU errors investigation and Root-Mean-Square (RMS) values for gantry and collimator errors investigation. RESULTS: MCS ranges values were: 0.10-0.20 for H&N, 0.21-0.40 for prostate and rectum, 0.41-1.00 for breast. From ROC curves, the Gamma Passing Rate (GPR) thresholds were: 87%, 92%, 99% for H&N, prostate and rectum, and breast, respectively. The 1.5%/1.5 mm/local criteria were adopted for the γ-analysis. LW sensitivity in detecting the introduced errors was higher when compared to Oct4D: 48.5% vs 30.4% respectively. CONCLUSIONS: LW can be considered useful complement to phantom-based delivery QA of IMRT/VMAT plans. The MCS tool is effective in detecting over or under modulated plans prior to pre-treatment QA. However, rigorous and routinely machine QCs are recommended.

Reorganization of the structural connectome in primary open angle Glaucoma.

Primary open angle Glaucoma (POAG) is one of the most common causes of permanent blindness in the world. Recent studies have suggested the hypothesis that POAG is also a central nervous system disorder which may result in additional (i.e., extra-ocular) involvement. The aim of this study is to assess possible structural, whole-brain connectivity alterations in POAG patients. We evaluated 23 POAG patients and 15 healthy controls by combining multi-shell diffusion weighted imaging, multi-shell, multi-tissue probabilistic tractography, graph theoretical measures and a recently designed 'disruption index', which evaluates the global reorganization of brain networks. We also studied the associations between the whole-brain structural connectivity measures and indices of visual acuity including the field index (VFI) and two Optical Coherence Tomography (OCT) parameters, namely the Macula Ganglion Cell Layer (MaculaGCL) and Retinal Nerve Fiber Layer (RNFL) thicknesses. We found both global and local structural connectivity differences between POAG patients and controls, which extended well beyond the primary visual pathway and were localized in the left calcarine gyrus (clustering coefficient p = 0.036), left lateral occipital cortex (clustering coefficient p = 0.017, local efficiency p = 0.035), right lingual gyrus (clustering coefficient p = 0.009), and right paracentral lobule (clustering coefficient p = 0.009, local efficiency p = 0.018). Group-wise (clustering coefficient, p = 6.59∙10-7 and local efficiency p = 6.23·10-8) and subject-wise disruption indices (clustering coefficient, p = 0.018 and local efficiency, p = 0.01) also differed between POAG patients and controls. In addition, we found negative associations between RNFL thickness and local measures (clustering coefficient, local efficiency and strength) in the right amygdala (local efficiency p = 0.008, local strength p = 0.016), right inferior temporal gyrus (clustering coefficient p = 0.036, local efficiency p = 0.042), and right temporal pole (local strength p = 0.008). Overall, we show, in patients with POAG, a whole-brain structural reorganization that spans across a variety of brain regions involved in visual processing, motor control, and emotional/cognitive functions. We also identified a pattern of brain structural changes in relation to POAG clinical severity. Taken together, our findings support the hypothesis that the reduction in visual acuity from POAG can be driven by a combination of local (i.e., in the eye) and more extended (i.e., brain) effects.

Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma.

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp-Parrish-Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients.

Quantitative analysis of basal and interim PET/CT images for predicting tumor recurrence in patients with Hodgkin's lymphoma.

OBJECTIVES: The qualitative analysis of interim PET has been reported to be useful for predicting the outcome of Hodgkin's lymphoma (HL) after chemotherapy. As the next step, our study aims to present a quantitative analysis on the basis of both a basal (PET/CT0) and an interim (PET/CT2) scan to improve the prognostic value of imaging in HL patients. PATIENTS AND METHODS: A cohort of 68 patients undergoing a basal and an interim scan with F-fluorodeoxyglucose after two cycles of chemotherapy consisting of adriamycin, bleomycin, vinblastine, and dacarbazine were examined. Two subsets of patients with a positive and a negative interim scan were selected. RESULTS: In patients with a negative scan, a total of 108 lymph node lesions showing a good response to chemotherapy were contoured, whereas in the remaining patients with positive scans, six responder and 12 relapsing lymph node lesions were contoured. Standardized uptake value (SUV) and Hounsfield unit (HU) values were included in the volumes contoured on coregistered basal and interim scans and included in a database. A linear regression model was used to identify the predictor of relapse at the lesion level. The support vector machine analysis and bootstrap approach were used to determine the model capability. The predictive models were presented as nomograms on the basis of basal or both basal and interim studies. SUV at the basal/interim study and basal HU values were predictors of a poor prognosis. In particular, the higher points were associated with lower values of SUV and HU at baseline and the higher values of SUV at the interim study. Using the bootstrap and support vector machine approach, the cut-off of the model increased up to 89%. CONCLUSION: The novel tool enables estimation of the risk of tumor relapse after chemotherapy in HL patients on the basis of basal and interim PET/CT scans including SUV and densitometric information.

The transcriptome and miRNome profiling of glioblastoma tissues and peritumoral regions highlights molecular pathways shared by tumors and surrounding areas and reveals differences between short-term and long-term survivors.

Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor, driving patients to death within 15 months after diagnosis (short term survivors, ST), with the exception of a small fraction of patients (long term survivors, LT) surviving longer than 36 months. Here we present deep sequencing data showing that peritumoral (P) areas differ from healthy white matter, but share with their respective frankly tumoral (C) samples, a number of mRNAs and microRNAs representative of extracellular matrix remodeling, TGFß and signaling, of the involvement of cell types different from tumor cells but contributing to tumor growth, such as microglia or reactive astrocytes. Moreover, we provide evidence about RNAs differentially expressed in ST vs LT samples, suggesting the contribution of TGF-ß signaling in this distinction too. We also show that the edited form of miR-376c-3p is reduced in C vs P samples and in ST tumors compared to LT ones. As a whole, our study provides new insights into the still puzzling distinction between ST and LT tumors, and sheds new light onto that "grey" zone represented by the area surrounding the tumor, which we show to be characterized by the expression of several molecules shared with the proper tumor mass.