Radiological properties of 3D printed materials in kilovoltage and megavoltage photon beams

PurposeThis study evaluates the radiological properties of different 3D printing materials for a range of photon energies, including kV and MV CT imaging and MV radiotherapy beams.MethodsThe CT values of a number of materials were measured on an Aquilion One CT scanner at 80 kVp, 120 kVp and a Tomotherapy Hi Art MVCT imaging beam. Attenuation of the materials in a 6 MV radiotherapy beam was investigated.ResultsPlastic filaments printed with various infill densities have CT values of −743 ± 4, −580 ± 1 and −113 ± 3 in 120 kVp CT images which approximate the CT values of low-density lung, high-density lung and soft tissue respectively. Metal-infused plastic filaments printed with a 90% infill density have CT values of 658 ± 1 and 739 ± 6 in MVCT images which approximate the attenuation of cortical bone. The effective relative electron density RED_eff is used to describe the attenuation of a megavoltage treatment beam, taking into account effects relating to the atomic number and mass density of the material. Plastic filaments printed with a 90% infill density have RED_eff values of 1.02 ± 0.03 and 0.94 ± 0.02 which approximate the relative electron density RED of soft tissue. Printed resins have RED_eff values of 1.11 ± 0.03 and 1.09 ± 0.03 which approximate the RED of bone mineral.Conclusions3D printers can model a variety of body tissues which can be used to create phantoms useful for both imaging and dosimetric studies.     

Natural language processing of radiology reports for the detection of thromboembolic diseases and clinically relevant incidental findings

Background

Natural Language Processing (NLP) has been shown effective to analyze the content of radiology reports and identify diagnosis or patient characteristics. We evaluate the combination of NLP and machine learning to detect thromboembolic disease diagnosis and incidental clinically relevant findings from angiography and venography reports written in French. We model thromboembolic diagnosis and incidental findings as a set of concepts, modalities and relations between concepts that can be used as features by a supervised machine learning algorithm. A corpus of 573 radiology reports was de-identified and manually annotated with the support of NLP tools by a physician for relevant concepts, modalities and relations. A machine learning classifier was trained on the dataset interpreted by a physician for diagnosis of deep-vein thrombosis, pulmonary embolism and clinically relevant incidental findings. Decision models accounted for the imbalanced nature of the data and exploited the structure of the reports.

Results

The best model achieved an F measure of 0.98 for pulmonary embolism identification, 1.00 for deep vein thrombosis, and 0.80 for incidental clinically relevant findings. The use of concepts, modalities and relations improved performances in all cases.

Conclusions

This study demonstrates the benefits of developing an automated method to identify medical concepts, modality and relations from radiology reports in French. An end-to-end automatic system for annotation and classification which could be applied to other radiology reports databases would be valuable for epidemiological surveillance, performance monitoring, and accreditation in French hospitals.     

Global Effects of DDX3 Inhibition on Cell Cycle Regulation Identified by a Combined Phosphoproteomics and Single Cell Tracking Approach

DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24?hours with RK-33 or vehicle control. Changes in phosphopeptide abundance were analyzed with quantitative mass spectrometry using isobaric mass tags (Tandem Mass Tags). At the proteome level we mainly observed changes in mitochondrial translation, cell division pathways and proteins related to cell cycle progression. Analysis of the phosphoproteome indicated decreased CDK1 activity after RK-33 treatment. To further evaluate the effect of DDX3 inhibition on cell cycle progression over time, we performed timelapse microscopy of Fluorescent Ubiquitin Cell Cycle Indicators labeled cells after RK-33 or siDDX3 exposure. Single cell tracking indicated that DDX3 inhibition resulted in a global delay in cell cycle progression in interphase and mitosis. In addition, we observed an increase in endoreduplication. Overall, we conclude that DDX3 inhibition affects cells in all phases and causes a global cell cycle progression delay.     

肝硬化患者胃排空的放射学研究

目的 :用放射学方法研究肝硬化患者的胃排空情况。资料与方法 :对 2 0例经临床和实验室检查证实的肝硬化患者及 18例健康志愿者摄入不透X线标示物及标准餐后 ,用数字成像X线机腹部摄片测定 6小时的胃排空情况。结果 :2 0例肝硬化患者 6小时胃排空率为 6 5 % ,而 18例健康志愿者为 10 0 % ,两者有显著性差异 (P <0 0 1) ,显示肝硬化患者有明显的胃运动障碍。结论 :用摄入不透X线标示物及标准餐的放射学方法检查肝硬化患者的胃排空时间 ,是一种简单易行、准确可靠的诊断方法     

Multiple-trait selection for radiographic health of the limbs, conformation and performance in Warmblood riding horses

Information on 26 434 German Warmblood horses born between 1992 and 2001 was used for multivariate genetic analyses of radiographic health, conformation and performance traits to compare different modes of single- and multiple-trait selection of sires. Results of standardized radiological examinations of 5155 Hanoverian Warmblood horses, conformation evaluations from studbook inspections of 20 603 mares, and performance evaluations from mare performance tests and auction horse inspections of 16 098 horses were used for multivariate genetic analyses. Genetic parameters were estimated with restricted maximum likelihood (REML), and relative breeding values (RBV) were predicted with best linear unbiased prediction (BLUP) in multivariate linear animal models for four radiographic health traits, three conformation traits and five performance traits. Heritability estimates for osseous fragments in fetlock joints (OFF), osseous fragments in hock joints (OFH), deforming arthropathy in hock joints (DAH) and distinct radiographic findings in the navicular bones (DNB) ranged between 0.15 and 0.35 after transformation to the liability scale. Front limb conformation, hind limb conformation, withers height, walk, trot, canter, rideability and free jumping showed heritabilities between 0.09 and 0.49 and additive genetic correlations with OFF, OFH, DAH and DNB ranging between -0.53 and +0.52. Selection of sires was based on RBV or combinations of RBV, with selection for individual traits or traits from one of the three considered trait groups being considered as single-trait selection, and selection for traits from more than one trait group being considered as multiple-trait selection. The selection modes were compared by means of the expected selection response after one generation, calculated as the relative change in the prevalences of the radiographic findings or the mean conformation or performance scores in the offspring of the selected sires when compared with the offspring of all sires. The prevalences of OFF, OFH, DAH and DNB decreased by 30% to 57% after single-trait selection and 14% to 29% after multiple-trait selection, while mean conformation and performance scores increased by up to 4%. The results indicated that it is possible to simultaneously improve the radiographic health of the limbs, limb conformation, quality of gaits and rideability. However, genetic progress in free jumping ability and style could only be achieved by single- or multiple-trait selection with focus on jumping performance.     

Freedom of Choice About Incidental Findings Can Frustrate Participants' True Preferences

Ethicists, regulators and researchers have struggled with the question of whether incidental findings in genomics studies should be disclosed to participants. In the ethical debate, a general consensus is that disclosed information should benefit participants. However, there is no agreement that genetic information will benefit participants, rather it may cause problems such as anxiety. One could get past this disagreement about disclosure of incidental findings by letting participants express their preferences in the consent form. We argue that this freedom of choice is problematic. In transferring the decision to participants, it is assumed that participants will understand what they decide about and that they will express what they truly want. However, psychological findings about people's reaction to probabilities and risk have been shown to involve both cognitive and emotional challenges. People change their attitude to risk depending on what is at stake. Their mood affects judgments and choices, and they over‐ and underestimate probabilities depending on whether they are low or high. Moreover, different framing of the options can steer people to a specific choice. Although it seems attractive to let participants express their preferences to incidental findings in the consent form, it is uncertain if this choice enables people to express what they truly prefer. In order to better understand the participants' preferences, we argue that future empirical work needs to confront the participant with the complexity of the uncertainty and the trade‐offs that are connected with the uncertain predictive value of genetic risk information.     

Immunohistochemical distribution of epithelioid cell, myofibroblast, and transforming growth factor-beta1 in the granuloma caused by Mycobacterium avium intracellulare complex pulmonary infection

The present study was designed to evaluate the distribution of epithelioid cells, myofibroblasts, and TGF-beta1 in the formation of granuloma caused by Mycobacterium avium intracellulare complex (MAC) lung infection. A retrospective study was performed for 9 cases of positive MAC culture in which lung resections were performed between January 1989 and August 1999. Resected lung specimens were evaluated histologically and immunohistochemically for CD68 (stain for monocytes and macrophages, and epithelioid cells) and alpha-smooth muscle actin as well as vimentin (stain for myofibroblasts), and TGF-beta1 was performed. When granuloma was initially formed, no myofibroblasts were found, but as caseous necrosis appeared, the thin epithelioid cell layer was detected and the outer myofibroblast layer gradually became thick. In the cavitary wall, the layer of epithelioid cells and multinucleated giant cells surrounded necrosis, and was associated with the outer layer of myofibroblasts. In addition, the anti-TGF-beta1 antibody stained the cytoplasm of epithelioid cells and multinucleated giant cells, preceding the advent of myofibroblasts. In summary, our present study evaluated distributions of epithelioid cells, myofibroblasts, and TGF-beta along with the morphogenesis of granuloma, and clearly demonstrated the immunohistochemical difference between granuloma with caseous necrosis and granulomas without caseous necrosis.     

Multiple Administrations of 64Cu-ATSM as a Novel Therapeutic Option for Glioblastoma: a Translational Study Using Mice with Xenografts

Glioblastoma is the most aggressive malignant brain tumor in humans and is difficult to cure using current treatment options. Hypoxic regions are frequently found in glioblastoma, and increased levels of hypoxia are associated with poor clinical outcomes of glioblastoma patients. Hypoxia plays important roles in the progression and recurrence of glioblastoma because of drug delivery deficiencies and induction of hypoxia-inducible factor-1α in tumor cells, which lead to poor prognosis. We focused on a promising hypoxia-targeted internal radiotherapy agent, ⁶⁴Cu-diacetyl-bis (N⁴-methylthiosemicarbazone) (⁶⁴Cu-ATSM), to address the need for additional treatment for glioblastoma. This compound can target the overreduced state under hypoxic conditions within tumors. Clinical positron emission tomography studies using radiolabeled Cu-ATSM have shown that Cu-ATSM accumulates in glioblastoma and its uptake is associated with high hypoxia-inducible factor-1α expression. To evaluate the therapeutic potential of this agent for glioblastoma, we examined the efficacy of ⁶⁴Cu-ATSM in mice bearing U87MG glioblastoma tumors. Administration of single dosage (18.5, 37, 74, 111, and 148 MBq) and multiple dosages (37 MBq × 4) of ⁶⁴Cu-ATSM was investigated. Single administration of ⁶⁴Cu-ATSM in high-dose groups dose-dependently inhibited tumor growth and prolonged survival, with slight and reverse signs of adverse events. Multiple dosages of ⁶⁴Cu-ATSM remarkably inhibited tumor growth and prolonged survival. By splitting the dose of ⁶⁴Cu-ATSM, no adverse effects were observed. Our findings indicate that multiple administrations of ⁶⁴Cu-ATSM have effective antitumor effects in glioblastoma without side effects, indicating its potential for treating this fatal disease.     

Tail lesions in fattening pigs: relationships with postmortem meat inspection and influence of a tail biting management tool

Tail biting is a major welfare and economic problem in intensive pig production. The objectives of this study were to (1) determine tail lesion prevalence at a German abattoir, (2) test for associations between meat inspection findings and tail lesions, (3) assess the agreement between tail necrosis recorded during meat inspection and scored from pictures and (4) test whether the tail biting management tool ‘Schwanzbeiß-Interventions-Programm’ (SchwIP) had an effect on tail lesion prevalence. A total of three observers scored tail lesions from pictures of 43 328 pigs from 32 farms where SchwIP had been applied, and of 36 626 pigs from 32 control farms. Tail lesions were classified as score 0: no visible lesion, score 1: mild lesion, score 2: severe lesion and score 3: necrosis. In addition, complete loss of tail (CL) was recorded. Tail necrosis was the only tail-related carcase finding recorded by meat inspectors. (1) Tail lesion prevalences in pigs from control farms were 23.6% for score 1, 1.02% for score 2, 0.55% for score 3 and 0.41% for CL. The combined prevalence of any lesion and/or CL was 25.4%. (2) Pleurisy, lung findings, signs of inflammation in the legs, arthritis and abscesses were the most frequent meat inspection findings (prevalences of 8.46%, 8.09%, 2.99%, 0.83% and 0.23%, respectively; n=79 954 pigs). Leg inflammation, arthritis and abscesses were more prevalent in pigs with tail lesions of any degree compared with pigs without tail lesions (3.39% v. 2.83%, 1.06% v. 0.75% and 0.39% v. 0.17%, respectively; all P<0.001, n=79 954 pigs). Pigs with severe tail lesions also had more lung findings (2.00% v. 0.17%, P<0.001). (3) Tail necrosis scored during meat inspection resulted in lower prevalence than scored from pictures (0.22% v. 0.69%; n=79 954 SchwIP and control farm pigs). (4) Although tail lesion prevalence was significantly higher in pigs from SchwIP than in pigs from control farms during the first 3 months (32.2% v. 23.8%, P=0.015), it was not significantly higher during the remainder of the year (22.6 v. 26.9, 24.4 v. 21.4 and 24.0 v. 28.0, second, third and fourth quarters, respectively). In conclusion, meat inspection results in much lower tail lesion prevalences than tail lesion assessment from pictures, even if only the category ‘necrosis’ is compared. Advising farms on tail biting using the management tool SchwIP helped to decrease the prevalence of tail lesions on problem farms.     

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition

The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult. New radiological tools are emerging, however, that allow one to noninvasively investigate the function of select groups of adult-born neurons through accurate and precise anatomical targeting in small animals. Focal ionizing radiation inhibits the birth and differentiation of new neurons, and allows targeting of specific neural progenitor regions. In order to illuminate the potential functional role that adult hypothalamic neurogenesis plays in the regulation of physiological processes, we developed a noninvasive focal irradiation technique to selectively inhibit the birth of adult-born neurons in the hypothalamic median eminence. We describe a method for Computer tomography-guided focal irradiation (CFIR) delivery to enable precise and accurate anatomical targeting in small animals. CFIR uses three-dimensional volumetric image guidance for localization and targeting of the radiation dose, minimizes radiation exposure to nontargeted brain regions, and allows for conformal dose distribution with sharp beam boundaries. This protocol allows one to ask questions regarding the function of adult-born neurons, but also opens areas to questions in areas of radiobiology, tumor biology, and immunology. These radiological tools will facilitate the translation of discoveries at the bench to the bedside.