Volume Definition Research Articles

3D printed anthropomorphic left ventricular myocardial phantom for nuclear medicine imaging applications

BackgroundAnthropomorphic torso phantoms, including a cardiac insert, are frequently used to investigate the imaging performance of SPECT and PET systems. These phantom solutions are generally featuring a simple anatomical representation of the heart. 3D printing technology paves the way to create cardiac phantoms with more complex volume definition. This study aimed to describe how a fillable left ventricular myocardium (LVm) phantom can be manufactured using geometry extracted from a patient image.MethodsThe LVm of a healthy subject was segmented from 18F-FDG attenuation corrected PET image set. Two types of phantoms were created and 3D printed using polyethylene terephthalate glycol (PETG) material: one representing the original healthy LVm, and the other mimicking myocardium with a perfusion defect. The accuracy of the LVm phantom production was investigated by high-resolution CT scanning of 3 identical replicas. 99mTc SPECT acquisitions using local cardiac protocol were performed, without additional scattering media (“in air” measurements) for both phantom types. Furthermore, the healthy LVm phantom was inserted in the commercially available DataSpectrum Anthropomorphic Torso Phantom (“in torso” measurement) and measured with hot background and hot liver insert.ResultsPhantoms were easy to fill without any air-bubbles or leakage, were found to be reproducible and fully compatible with the torso phantom. Seventeen segments polar map analysis of the "in air” measurements revealed that a significant deficit in the distribution appeared where it was expected. 59% of polar map segments had less than 5% deviation for the "in torso” and "in air” measurement comparison. Excluding the deficit area, neither comparison had more than a 12.4% deviation. All the three polar maps showed similar apex and apical region values for all configurations.ConclusionsFillable anthropomorphic 3D printed phantom of LVm can be produced with high precision and reproducibility. The 3D printed LVm phantoms were found to be suitable for SPECT image quality tests during different imaging scenarios. The flexibility of the 3D printing process presented in this study provides scalable and anthropomorphic image quality phantoms in nuclear cardiology imaging.

Ways Forward in Preventing Severe Maternal Morbidity and Maternal Health Inequities: Conceptual Frameworks, Definitions, and Data, from a Population Health Perspective.

Ways Forward in Preventing Severe Maternal Morbidity and Maternal Health Inequities: Conceptual Frameworks, Definitions, and Data, from a Population Health Perspective.

Exploring bulk volume, particle size and particle motion definitions to increase the predictive ability of in vitro dissolution simulations

The definition of the local dissolution environment is central to accurate particle dissolution simulation, and is determined by the apparatus and conditions used. In the flow-through apparatus dissolution occurs in the cell, often in a low velocity environment, with the reservoir considered the relevant volume for dissolution kinetics. Dissolution simulations were conducted using a reduced-order model based on the Ranz-Marshall correlation for mass transfer from spherical particles. Using ibuprofen as a model drug, the effect of defining a local volume to simulate dynamic bulk concentration conditions in the flow-through and paddle apparatus was assessed by comparing use of a near particle volume (NPV), extending a distance of one radius from the particle surface, with a flow-through apparatus cell volume or paddle apparatus vessel volume as the relevant instantaneous volume for dissolution. The instantaneous inlet concentration to NPV or cell volume is the reservoir/vessel concentration at that simulation time point, reflecting the continuous input to the cell of more dilute solution from the reservoir (closed system). Additionally, inputting particle size distribution (PSD) instead of a median particle size (MPS) and enabling or disabling particle motion were investigated, in two media (resulting in low and high solubility) and with two fluid velocity conditions in each apparatus.The NPV predicted effects of fluid velocity differences on dissolution in the high solubility medium in the flow-through apparatus, but had no effect on predictive ability in the paddle apparatus. In both apparatuses, simulations were reasonable for the high solubility environment but underpredicted dissolution in the low solubility environment. The PSD option and disabling particle motion increased the predictive ability of the simulations in low solubility media in the flow-through apparatus. The results highlight the necessity to incorporate the local dynamic dissolution conditions in the flow-through apparatus for accurate dissolution simulation, and the challenges of defining an effective particle size for dissolution simulation and of reflecting hydrodynamic complexity in simulating dissolution in the paddle apparatus.

Increased specimen minimum volume reduces turnaround time and hemolysis

Quantity not sufficient (QNS) specimens with minimal blood volume for testing are common in clinical laboratories. However, there is no universal definition of minimum volume for a QNS specimen and little data is available addressing the impact of QNS / low volume specimens on turnaround time (TAT) and sample hemolysis. We compared the TAT and hemolysis index from samples ≤1.0 mL to all specimens received and quantified the number of specimens with reduced blood volume. A new QNS policy requiring ≥1.5 mL of sample in a blood tube for laboratory analysis was implemented and the results were assessed by sample hemolysis and TAT. The median laboratory TAT for samples with ≤1.0 mL of blood was 61 min (Interquartile Range, IQR: 50–82), in contrast to 28 min (26–34) for all samples. The hemolysis index for samples ≤1.0 mL was 112 (65–253) and 15 (8–29) for all samples. Requirement of a minimum volume of 1.5 mL of blood resulted in the proportion of samples with TAT ≥ 60 min to decrease from 10.4% to 4.24% in the ED, and for specimens cancelled due to hemolysis to decrease from 4.24% to 3.38%. This policy was introduced hospital wide with similar effects. Together, we correlate limited specimen volume with an increase in laboratory TAT and hemolysis. Implementation of a QNS policy of ≥1.5 mL and provider education provided a significant and durable reduction in TAT and specimen hemolysis.

Reappraisal of multimodality imaging for improved Radiation Therapy (RT) target volume determination of recurrent Oral Squamous Cell Carcinoma (OSCC): An original article

Objective: Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most frequent cancer sites around the globe. Within the heterogeneous group of HNSCC, Oral Squamous Cell Carcinoma (OSCC) deserves the utmost attention as an important subsite. Despite multimodality management, recurrence of OSCC is not uncommon. RT may play an integral role as part of initial management or as adjunctive therapy, or for treatment of recurrent disease. In this study, we evaluate multimodality imaging-based RT treatment volume definition for irradiation of recurrent OSCC. Materials and methods: Multimodality imaging-based RT treatment volume definition for radiotherapeutic management of recurrent OSCC was assessed. RT target volume determination by incorporation of Magnetic Resonance Imaging (MRI) or by Computed Tomography (CT)-simulation images only has been evaluated and comparative analysis has been performed for patients receiving salvage RT for recurrent OSCC. Results: Ground truth target volume has been found to be identical with treatment volume definition by CT-MR fusion-based imaging. Conclusion: Incorporation of MRI in target and treatment volume definition may improve target and treatment volume definition for recurrent OSCC.

Gross Tumor Volume Definition and Comparative Assessment for Esophageal Squamous Cell Carcinoma From 3D 18F-FDG PET/CT by Deep Learning-Based Method.

BackgroundThe accurate definition of gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) can promote precise irradiation field determination, and further achieve the radiotherapy curative effect. This retrospective study is intended to assess the applicability of leveraging deep learning-based method to automatically define the GTV from 3D 18F-FDG PET/CT images of patients diagnosed with ESCC.MethodsWe perform experiments on a clinical cohort with 164 18F-FDG PET/CT scans. The state-of-the-art esophageal GTV segmentation deep neural net is first employed to delineate the lesion area on PET/CT images. Afterwards, we propose a novel equivalent truncated elliptical cone integral method (ETECIM) to estimate the GTV value. Indexes of Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean surface distance (MSD) are used to evaluate the segmentation performance. Conformity index (CI), degree of inclusion (DI), and motion vector (MV) are used to assess the differences between predicted and ground truth tumors. Statistical differences in the GTV, DI, and position are also determined.ResultsWe perform 4-fold cross-validation for evaluation, reporting the values of DSC, HD, and MSD as 0.72 ± 0.02, 11.87 ± 4.20 mm, and 2.43 ± 0.60 mm (mean ± standard deviation), respectively. Pearson correlations (R2) achieve 0.8434, 0.8004, 0.9239, and 0.7119 for each fold cross-validation, and there is no significant difference (t = 1.193, p = 0.235) between the predicted and ground truth GTVs. For DI, a significant difference is found (t = −2.263, p = 0.009). For position assessment, there is no significant difference (left-right in x direction: t = 0.102, p = 0.919, anterior–posterior in y direction: t = 0.221, p = 0.826, and cranial–caudal in z direction: t = 0.569, p = 0.570) between the predicted and ground truth GTVs. The median of CI is 0.63, and the gotten MV is small.ConclusionsThe predicted tumors correspond well with the manual ground truth. The proposed GTV estimation approach ETECIM is more precise than the most commonly used voxel volume summation method. The ground truth GTVs can be solved out due to the good linear correlation with the predicted results. Deep learning-based method shows its promising in GTV definition and clinical radiotherapy application.

Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis.

To explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS). We retrospectively studied 345 patients with SPMS enrolled in the MS-SMART trial. They underwent brain MRI at baseline and at 24 and 96 weeks. Definite SELs were defined as concentrically expanding T2 lesions, as assessed by nonlinear deformation of volumetric T1-weighted images. Associations of SEL volumes with other MRI metrics and disability were assessed through Pearson correlations and regression analyses. Averaged across patients, 29% of T2 lesions were classified as being definite SELs. A greater volume of definite SELs correlated with a higher total baseline T2 lesion volume (r = 0.55, p < 0.001) and percentage brain volume reduction (r = -0.26, p < 0.001), a higher number of new persisting T1 black holes (r = 0.19, p < 0.001), and, in a subset of 106 patients, with a greater reduction in magnetization transfer ratio (adjusted difference 0.52, p < 0.001). In regression analyses, a higher definite SEL volume was associated with increasing disability, as assessed by the Expanded Disability Status Scale (β = 0.23, p = 0.020), z scores of the Multiple Sclerosis Functional Composite (β = -0.47, p = 0.048), Timed 25-Foot Walk Test (β = -2.10, p = 0.001), and Paced Auditory Serial Addition Task (β = -0.27, p = 0.006), and increased risk of disability progression (odds ratio 1.92, p = 0.025). Definite SELs represent almost one-third of T2 lesions in SPMS. They are associated with neurodegenerative MRI markers and related to clinical worsening, suggesting that they may contribute to disease progression and be a new target for therapeutic interventions.

Solvent-driven thiol protected luminescent cobalt nanoclusters

The choice of solvent in the wet chemical synthesis of metal nanoclusters plays a critical role in engineering the cluster size, stoichiometry composition, geometric configurations and activity via regulating the adsorption of thiol staple motifs over the core of these nanoclusters. Herein, we report a facile synthesis of thiophenol(TP) stabilized cobalt nanoclusters (CoNCs) in a DMSO medium by chemical reduction method. The significant impact of solvents over CoNCs was explored by altering the chemical environment of NCs with definite volume fractions of polar protic (Chloroform, Acetic acid) and aprotic (DMSO, Acetone) solvents. The tunable H-bonding ability of polar protic solvents with varying dipole moments induces changes in the physicochemical properties of CoNCs. On the other hand, the use of polar aprotic solvents influences the Co(II)-SR staple motifs to aggregate over CoNCs. The stability of CoNCs with aprotic solvent i.e., acetone was accompanied with etching, gives rise to the changes in the molecular composition leading to structure-property changes. The insights on solvent-dependent properties might be from the synergetic factors of hydrogen bonding and hydrophobic interactions between thiol and solvent molecules. The solvent-derived structure-property changes were confirmed using TEM, UV–visible absorption studies, XRD, FT-IR, Raman, MALDI-MS analysis, photoluminescence and lifetime decay studies. The PL emission peak of CoNCs in DMSO observed at 440 nm (blue emission) is red-shifted to 555 nm with greenish-yellow emission, while changing the environment with less polar aprotic acetone as a solvent. In the polar protic solvent environment, the crucial role of H-bonding interactions promotes the emission peak at 562 nm by activating a new emissive state along with 440 nm emission. The cytotoxicity examination of these CoNCs compounds on MCF-7 cells has indicated their biocompatibility and non-toxic property as an alternative agent for bioimaging and biolabeling for research aspects in in-vitro studies. This work addresses the impact of different polar solvent environments and their substantial dependency on the structure-property correlation of aromatic thiol stabilized cobalt nanoclusters and their applicability for cell imaging in biomedical research.

PowderMEMS-A Generic Microfabrication Technology for Integrated Three-Dimensional Functional Microstructures.

A comprehensive overview of PowderMEMS—a novel back-end-of-line-compatible microfabrication technology—is presented in this paper. The PowderMEMS process solidifies micron-sized particles via atomic layer deposition (ALD) to create three-dimensional microstructures on planar substrates from a wide variety of materials. The process offers numerous degrees of freedom for the design of functional MEMSs, such as a wide choice of different material properties and the precise definition of 3D volumes at the substrate level, with a defined degree of porosity. This work details the characteristics of PowderMEMS materials as well as the maturity of the fabrication technology, while highlighting prospects for future microdevices. Applications of PowderMEMS in the fields of magnetic, thermal, optical, fluidic, and electrochemical MEMSs are described, and future developments and challenges of the technology are discussed.

A novel semiautomated method for background activity and biological tumour volume definition to improve standardisation of 18F-FET PET imaging in glioblastoma

BackgroundMulticentre clinical trials evaluating the role of 18F-Fluoroethyl-l-tyrosine (18F-FET) PET as a diagnostic biomarker in glioma management have highlighted a need for standardised methods of data analysis. 18F-FET uptake normalised against background in the contralateral brain is a standard imaging technique to delineate the biological tumour volume (BTV). Quantitative analysis of 18F-FET PET images requires a consistent and robust background activity. Currently, defining background activity involves the manual selection of an arbitrary region of interest, a process that is subject to large variability. This study aims to eliminate methodological errors in background activity definition through the introduction of a semiautomated method for region of interest selection. A new method for background activity definition, involving the semiautomated generation of mirror-image (MI) reference regions, was compared with the current state-of-the-art method, involving manually drawing crescent-shape (gCS) reference regions. The MI and gCS methods were tested by measuring values of background activity and resulting BTV of 18F-FET PET scans of ten patients with recurrent glioblastoma multiforme generated from inputs provided by seven readers. To assess intra-reader variability, each scan was evaluated six times by each reader. Intra- and inter-reader variability in background activity and BTV definition was assessed by means of coefficient of variation.ResultsCompared to the gCS method, the MI method showed significantly lower intra- and inter-reader variability both in background activity and in BTV definition.ConclusionsThe proposed semiautomated MI method minimises intra- and inter-reader variability, providing a valuable approach for standardisation of 18F-FET PET quantitative parameters.Trial registration ANZCTR, ACTRN12618001346268. Registered 9 August 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374253

MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System.

Simple SummaryThe hybrid magnetic resonance imaging and medical linear accelerator (MR-Linac) systems are expected to revolutionize radiation therapy, uniquely offering high quality soft-tissue contrast and fast imaging to facilitate the online re-planning and guidance of the treatment delivery. While the clinical procedures for stereotactic body radiotherapy are well-established for conventional linacs (with their strengths and weaknesses), they still require significant development and refinement for the MR-Linac systems. Adjustment of fractionation schemes including clinical goals, patient selection, organ motion management, treatment session length, staff logistics, and overall complexity of the online re-planning sessions are key factors that drive the adoption of MR-Linac technologies. In this report, we present the clinical implementation of an MRI-guided radiation therapy workflow, which was used to treat 16 upper gastro-intestinal cancer patients on a 1.5 T MR-Linac platform. The workflow was proven to be feasible for a wide range of clinical scenarios, and the overall treatment session time was significantly reduced as tasks were optimized and the clinical team gradually gained expertise.Purpose: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow’s clinical feasibility and early experience in the case of 16 liver and pancreas patients. Methods: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. Results: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70–90 min for a single fraction and 55–90 min for five fractions. The pancreas sessions were 54–85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9–96.1% and 99/95.4–100%, respectively. Conclusion: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics.

Several definitions have attempted to stratify metastatic castrate-sensitive prostate cancer (mCSPC) into low and high-volume states. However, at this time, comparison of these definitions is limited. Here we aim to compare definitions of metastatic volume in mCSPC with respect to clinical outcomes and mutational profiles. We performed a retrospective review of patients with biochemically recurrent or mCSPC whose tumors underwent somatic targeted sequencing. 294 patients were included with median follow-up of 58.3 months. Patients were classified into low and high-volume disease per CHAARTED, STAMPEDE, and two numeric (≤3 and ≤5) definitions. Endpoints including radiographic progression-free survival (rPFS), time to development of castration resistance (tdCRPC), and overall survival (OS) were evaluated with Kaplan-Meier survival curves and log-rank test. The incidence of driver mutations between definitions were compared. Median OS and tdCRPC were shorter for high-volume than low-volume disease for all four definitions. In the majority of patients (84.7%) metastatic volume classification did not change across all four definitions. High volume disease was significantly associated with worse OS for all four definitions (CHAARTED: HR 2.89; p < 0.01, STAMPEDE: HR 3.82; p < 0.01, numeric ≤3: HR 4.67; p < 0.01, numeric ≤5: HR 3.76; p < 0.01) however, were similar for high (p = 0.95) and low volume (p = 0.79) disease across all four definitions. Those with discordant classification tended to have more aggressive clinical behavior and mutational profiles. Patients with low-volume disease and TP53 mutation experienced a more aggressive course with rPFS more closely mirroring high-volume disease. The spectrum of mCSPC was confirmed across four different metastatic definitions for clinical endpoints and genetics. All definitions were generally similar in classification of patients, outcomes, and genetic makeup. Given these findings, the simplicity of numerical definitions might be preferred, especially when integrating metastasis directed therapy. Incorporation of tumor genetics may allow further refinement of current metastatic definitions.

Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial

To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy. Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated. The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P=.014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P=.019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P=.06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P=.07). Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.

Multi-level direct crystal plasticity model of polycrystalline specimen: representative volume determination

Since the origination of solid mechanics as a scientific discipline, full-scale experiments on loading (deformation) of macro samples of shape and size corresponding to accepted standards have been used as the main tool to establish the laws of material behavior and determine certain physical and mechanical properties of materials. With the development of technologies and widespread miniaturization, experiments begin to be carried out on samples of meso- and micro scales. This leads to the question: below what sample sizes does a significant deviation of the average response of the samples begin? Therefore, authors introduce the definition of a sample representative volume as the minimum volume, when exceeding which the possible deviation of the mean response of the sample to the same load does not exceed the predetermined value. In order to determine representative volume of polycrystalline specimen numerical experiments on compression of polycrystalline specimens were carried out. The initial grain structure of the sample was formed by cutting cube into set of equal cubes, where each represented a grain. Then the grains were approximated by a set of finite elements using the Gmsh software package. In order to directly solve the boundary-value problem, a software package was used to implement an algorithm for solving the crystal elastoviscoplastic problem formulated in the rate-form by the finite element method. The resulting curve of the relative (relative to the mean values) standard deviation of stresses monotonously decreases with an increase in the number of grains, and the curve of the mean value has a complex shape with a rapid damping of fluctuations and also seem to reach a constant value.

Olfactory dysfunction and olfactory bulb volume in patients with deviated nasal septum

The purpose of the study is to demonstrate the possibility and information content of olfactory bulb volume measuring in healthy volunteers and patients with deviated nasal septum, as well as the relationship between the volume of the olfactory bulb and olfactory function. Material and methods. 28 men with deviated nasal septum aged 24 to 35 years (main group) and 21 clinically healthy volunteers, men aged 23 to 33 years (control group) were examined. All patients underwent checkup of the ENT organs and examinations on a 1.5 T MRI machine with 12-channel head coil. The sense of smell was examined using the extended Sniffin Sticks test (SST) (“Buerhard”, Hamburg, Germany) with the definition of 3 parameters: threshold, identification and discrimination. Results. In accordance with the design of the work, threshold, discrimination, identification subtests and MRI examination of the head were performed with the measurement of the olfactory bulb volume of patients in the main group and volunteers in the control group. In all participants in the control group was diagnosed normosmia in accordance with the TDI indicator, and in patients with deviated nasal septum – hyposmia. Olfactory function in patients deviated nasal septum was significantly lower on the narrower side as indicated for odor thresholds, odor recognition, and odor identification (P&lt;0.01). It was found that olfactory bulb volumes are larger on the wider side than on the narrower side (P&lt;0.01). Conclusion. Asymmetry in the size and volume of OB is observed only in patients with deviated nasal septum, it is absent in healthy volunteers. MRI visualization and morphometry of olfactory bulb, in addition to identifying of the nasal cavity, paranasal sinuses state, are informative in the process of preoperative examination of patients with deviated nasal septum. Olfactory bulb volume definition should be used for personalized diagnosis and quantitative assessment of olfactory dysfunction.

A Predictive Modeling Approach to Support the Overfill Volume Definition of Liquid-in-Vial Drug Products.

Liquid-in-vial drug products are typically overfilled to meet the label claim volume specification while taking into account losses in the container-closure system and withdrawal device. Any overfill volume setting requires justification. The aim of this study was to estimate the overfill volume required for a liquid drug product in a vial using a prediction model. Glass vials sized from 2R to 20R capacity were filled with sorbitol-based aqueous solutions having a viscosity at 20°C ranging from 1 to 40 mPa·s. Viscosity and vial neck diameter were shown to be the main contributors to the hold-up volume of sorbitol-based aqueous solutions in vial and withdrawal syringe. The hold-up volume of various molecules of therapeutic interest was successfully estimated using a model built from sorbitol-based aqueous solutions data. A total variability approach is proposed for estimating the overfill volume of liquid-in-vial drug products, taking into account the product hold-up volume in vial and withdrawal syringe, the filling variability, and the extractable volume test variability. This prediction model could provide a first guess of the fill volume range to be tested to support overfill volume definition.

Target volume definition for staple line recurrences of non-small cell lung cancer.

BackgroundStaple line (SL) recurrences of non-small cell lung cancer (NSCLC) are commonly treated with radiotherapy (RT), but the target volume definition — whole SL versus focused on recurrence — is unclear. The aim of the study was to determine the appropriate target volume for RT of SL recurrences.Materials and methodsTwenty-two consecutive patients (20 stage I, 2 stage II) treated with salvage RT for SL recurrences were retrospectively analyzed. Imaging features at the time of SL recurrence were evaluated to guide target volume definition.ResultsSurgeryAll patients had complete tumor resection (wedge resection in 10 (45%) and lobectomy in 12 (55%) patients). 14 (64%) patients had risk factors for recurrence, including surgical margins ≤ 2 cm, angiolymphatic and visceral pleural invasion.Salvage RTAfter a median 26 months (9–67), all 22 patients developed SL recurrence which was metabolically active on PET in all and biopsy-confirmed in 18/22 (82%) patients. All patients underwent RT targeting the location of the SL recurrence only. 13/22 (59%) patients had additional PE T-negative nodular or linear SL changes that were not included in the irradiated volume.Recurrence after RTAfter a median 17 months (9–34) 10/22 (45%) patients recurred either regionally 6/10 (60%), in the lungs 4/10 (40%) or distally 3/10 (30%). No patient recurred at the SL. Two-year overall and disease-free survival rates after RT were 71% and 65%, respectively.ConclusionRT to SL recurrences alone results in excellent local control. Additional treatment to reduce regional and distant recurrences should be considered.

ProCaLung – Peer review in stage III, mediastinal node-positive, non-small-cell lung cancer: How to benchmark clinical practice of nodal target volume definition and delineation in Belgium☆

Background and purposeThe Quality Assurance project for stage III non-small cell lung cancer radiotherapy ProCaLung performed a multicentric two-step exercise evaluating mediastinal nodal Target Volume Definition and Delineation (TVD) variability and the opportunity for standardization. The TVD variability before and after providing detailed guidelines and the value of qualitative contour reviewing before applying quantitative measures were investigated. Materials and methodsThe case of a patient with stage III NSCLC and involved mediastinal lymph nodes was used as a basis for this study. Twenty-two radiation oncologists from nineteen centers in Belgium and Luxembourg participated in at least one of two phases of the project (before and after introduction of ProCaLung contouring guidelines). The resulting thirty-three mediastinal nodal GTV and CTV contours were then evaluated using a qualitative-before-quantitative (QBQ) approach. First, a qualitative analysis was performed, evaluating adherence to most recent guidelines. From this, a list of observed deviations was created and these were used to evaluate contour conformity. The second analysis was quantitative, using overlap and surface distance measures to compare contours within qualitative groups and between phases. A ‘most robust’ reference volume for these analyses was created using the STAPLE-algorithm and an averaging method. ResultsFive GTV and seven CTV qualitative groups were identified. Second step contours were more often in higher-conformity groups (p = 0.012 for GTV and p = 0.024 for CTV). Median Residual Mean Square Distances improved from 2.34 mm to 1.36 mm for GTV (p = 0.01) and from 4.53 mm to 1.58 mm for CTV (p < 0.0001). Median Dice coefficients increased from 0.81 to 0.84 for GTV (p = 0.07) and from 0.82 to 0.89 for CTV (p ≤ 0.001). Using HC-contours only to generate references translated in more robust quantitative evaluations. ConclusionVariability of mediastinal nodal TVD was reduced after providing the ProCaLung consensus guidelines. A qualitative review was essential for providing meaningful quantitative measures.

Detection of earthflow dynamics using medium-resolution digital terrain models: Diachronic perspective of the Jovac earthflow, Southern Serbia

The paper presents and discusses the landslide research procedure related to the topography before and after its occurrence, using the comparative analysis of two medium-resolution digital terrain models. The case study is the Jovac mega-landslide—the largest landslide to occur in Serbia in the last 100 years, active for three days in February 1977. The indicators used to determine the volume and movement mechanism were the spatial distribution of elevation differences within the two digital terrain models (DTM), and the analysis of geomorphological features before the landslide. The obtained elevation differences allowed the definition of the approximate landslide volume: 11.6 × 106 m3. All the data obtained indicate that the movement mechanism falls into the category of earthflow.

AB004. Optimal delineation of the clinical target volume for thymomas in the postoperative setting: a multi-center study

Background: The detailed definition of the clinical target volume (CTV) for post-operative radiotherapy (PORT) for thymoma is largely unexplored. The aim of this study was to analyse the difference in CTV delineation between radiation oncologists (RTO) and surgeons.