Synchrotrons for hadron therapy, part 1

The treatment of cancer with accelerator beams has a long history with linacs, cyclotrons and now synchrotrons being exploited for this purpose. Treatment techniques can be broadly divided into the use of spread-out beams and scanned 'pencil' beams. The Bragg-peak behaviour of hadrons makes them ideal candidates for the latter. The combination of precisely focused 'pencil' beams with controllable penetration (Bragg peak) and high, radio-biological efficiency (light ions) opens the way to treating the more awkward tumours that are radio-resistant, complex in shape and lodged against critical organs. To accelerate light ions (probably carbon) with pulse-to-pulse energy variation, a synchrotron is the natural choice. The beam scanning system is controlled via an on-line measurement of the particle flux entering the patient and, for this reason, the beam spill must be extended in time (seconds) by a slow-extraction scheme. The quality of the dose intensity profile ultimately depends on the uniformity of the beam spill. This is the greatest challenge for the synchrotron, since slow-extraction schemes are notoriously sensitive. This paper reviews the extraction techniques, describes methods for smoothing the beam spill and outlines the implications for the extraction line and beam delivery system

Proton-Ion Medical Machine Study (PIMMS), 1

The Proton-Ion Medical Machine Study (PIMMS) group was formed following an agreement between the Med-AUSTRON (Austria) and the TERA Foundation (Italy) to combine their efforts in the design of a cancer therapy synchrotron. CERN agreed to host this study in its PS Division and a close collaboration was set up with GSI (Germany). The study group was later joined by Onkologie-2000 (Czech Republic). Effort was first focused on the theoretical understanding of slow extraction and the techniques required to produce a smooth beam spill for the conformal treatment of complex-shaped tumours with a sub-millimetre accuracy by active scanning with proton and carbon ion beams. Considerations for passive scanning were also included. The more general and theoretical aspects of the study are recorded in Part I and the more specific technical design considerations are presented in a second volume Part II. The PIMMS team started their work in January 1996 in the PS Division and continued for a period of three years

New Cretaceous empidoids and the Mesozoic dance fly revolution (Diptera: Empidoidea)

Dance flies and relatives (Empidoidea) are a diverse and ecologically important group of Diptera in nearly all modern terrestrial ecosystems. Their fossil record, despite being scattered, attests to a long evolutionary history dating back to the early Mesozoic. Here, we describe seven new species of Empidoidea from Cretaceous Kachin amber inclusions, assigning them to the new genus Electrochoreutes gen.n. (type species: Electrochoreutes trisetigerus sp.n.) based on unique apomorphies among known Diptera. Like many extant dance flies, the males of Electrochoreutes are characterized by species-specific sexually dimorphic traits, which are likely to have played a role in courtship. The fine anatomy of the fossils was investigated through high-resolution X-ray phase-contrast microtomography to reconstruct their phylogenetic affinities within the empidoid clade, using cladistic reasoning. Morphology-based phylogenetic analyses including a selection of all extant family- and subfamily-ranked empidoid clades along with representatives of all extinct Mesozoic genera, were performed using a broad range of analytical methods (maximum parsimony, maximum-likelihood and Bayesian inference). These analyses converged in reconstructing Electrochoreutes as a stem-group representative of the Dolichopodidae, suggesting that complex mating rituals evolved in this lineage during the Cretaceous

The use of pocket-size imaging devices: a position statement of the European Association of Echocardiography.

Pocket-size imaging devices are a completely new type of echo machines which have recently reached the market. They are very cheap, smartphone-size hand-held echo machines with limited technical capabilities. The aim of this European Association of Echocardiography (EAE) position paper is to provide recommendations on the use of pocket-size imaging devices in the clinical arena by profiling the educational needs of potential users other than cardiologists experts in echo. EAE recommendations about pocket-size imaging devices can be summarized in: (1) pocket-size imaging devices do not provide a complete diagnostic echocardiographic examination. The range of indications for their use is therefore limited. (2) Imaging assessment with pocket-size imaging devices should be reported as part of the physical examination of the patient. Image data should be stored according to the applicable national rules for technical examinations. (3) With the exception of cardiologists who are certified for transthoracic echocardiography according to national legislation, specific training and certification is recommended for all users. The certification should be limited to the clinical questions that can potentially be answered by pocket-size devices. (4) The patient has to be informed that an examination with the current generation of pocket-size imaging devices does not replace a complete echocardiogram.Peer reviewe

Evaluation of Left Atrial Size and Function: Relevance for Clinical Practice

Left atrial (LA) structural and functional evaluation have recently emerged as powerful biomarkers for adverse events in a variety of cardiovascular conditions. Moreover, noninvasive evaluation of LA pressure has gained importance in the characterization of the hemodynamic profile of patients. This review describes the methodology, benefits and pitfalls of measuring LA size and function by echocardiography and provides a brief overview of the prognostic utility of newer echocardiographic metrics of LA geometry and function (i.e., three-dimensional volumes, longitudinal strain, and phasic function parameters)

Discovery of Lebambromyia in Myanmar cretaceous amber: phylogenetic and biogeographic implications (Insecta, Diptera, Phoroidea)

Lebambromyia sacculifera sp. nov. is described from Late Cretaceous amber from Myan-mar, integrating traditional observation techniques and X-ray phase contrast microtomography. Lebambromyia sacculifera is the second species of Lebambromyia after L. acrai Grimaldi and Cumming, described from Lebanese amber (Early Cretaceous), and the first record of this taxon from Myanmar amber, considerably extending the temporal and geographic range of this genus. The new specimen bears a previously undetected set of phylogenetically relevant characters such as a postpedicel sacculus and a prominent clypeus, which are shared with Ironomyiidae and Eumuscomorpha. Our cladistic analyses confirmed that Lebambromyia represented a distinct monophyletic lineage related to Platypezidae and Ironomyiidae, though its affinities are strongly influenced by the interpretation and coding of the enigmatic set of features characterizing these fossil flies

Use of artificial intelligence to automatically predict the optimal patient-specific inversion time for late gadolinium enhancement imaging. Tool development and clinical validation

Introduction With the worldwide diffusion of cardiac magnetic resonance (CMR), demand on image quality has grown. CMR late gadolinium enhancement (LGE) imaging provides critical diagnostic and prognostic information, and guides management. The identification of optimal Inversion Time (TI), a time-sensitive parameter closely linked to contrast kinetics, is pivotal for correct myocardium nulling. However, determining the optimal TI can be challenging in some diseases and for less experienced operators. Purpose To develop and test an artificial intelligence tool to automatically predict the personalised optimal TI in LGE imaging. Methods The tool, named THAITI, consists of a Random Forest regression model. It considers, as input parameters, patient-specific TI determinants (age, gender, weight, height, kidney function, heart rate) and CMR scan-specific TI determinants (B0, contrast type and dose, time elapsed from contrast injection). THAITI was trained on 219 patients (3585 images) with mixed conditions who underwent CMR (1.5T; Gadobutrol; averaged, MOCO, free-breathing true-FISP IR [1]) for clinical reasons. The dataset was split with a 90–10 policy: 90% of data for training, and 10% for testing. THAITI’s hyperparameters were optimised by embedding k-fold cross validation into an evolutionary computation algorithm, and the best performing model was finally evaluated on the test set. A graphical user interface was also developed. Clinical validation was performed on 55 consecutive patients, randomised to experimental (THAITI-set TI) vs control (operator-set TI) group. Image quality was assessed blindly by 2 independent experienced operators by a 4-points Likert scale, and by means of the contrast/enhancement ratio (CER) (i.e., signal intensity of enhanced/remote myocardium ratio). Results In the testing set, the TI predicted by THAITI differed from the ground truth by ≥ 5ms in 16% of cases. At clinical validation, myocardial nulling quality did not differ between the experimental vs the control group either by CER or visual assessment, with an overall "optimal" or "good" nulling in 96% vs 93%, respectively. Conclusions Using main determinants of contrast kinetics, THAITI efficiently predicted the optimal TI for CMR-LGE imaging. The tool works as a stand-alone on laptops/mobile devices, not requiring adjunctive scanner technology and thus has great potential for diffusion, including in small or recently opened CMR services, and in low-resource settings. Additional development is ongoing to increase generalisability (multi-vendor, multi-sequence, multi-contrast) and to test its potential to further improve CMR-LGE image quality and reduce the need for repeated imaging for inexperienced operators. Figure 1. Top: THAITI interface. Bottom: examples of experimental group CMR-LGE imaging. Table 1. Control vs experimental group. Data expressed as absolute number (%), mean ± SD, median [IQR]. ⧧ T-test; * Chi-square

Proton-Ion Medical Machine Study (PIMMS), 2

The Proton-Ion Medical Machine Study (PIMMS) group was formed following an agreement between the Med-AUSTRON (Austria) and the TERA Foundation (Italy) to combine their efforts in the design of a cancer therapy synchrotron capable of accelerating either light ions or protons. CERN agreed to support and host this study in its PS Division. A close collaboration was also set up with GSI (Germany). The study group was later joined by Onkologie-2000 (Czech Republic). Effort was first focused on the theoretical understanding of slow extraction and the techniques required to produce a smooth beam spill for the conformal treatment of complex-shaped tumours with a sub-millimetre accuracy by active scanning with proton and carbon ion beams. Considerations for passive beam spreading were also included for protons. The study has been written in two parts. The more general and theoretical aspects are recorded in Part I and the specific technical design considerations are presented in the present volume, Part II. An accompanying CD-ROM contains supporting publications made by the team and data files for calculations. The PIMMS team started its work in January 1996 in the PS Division and continued for a period of four years

An atypical case of pulmonary embolism from a jugular vein

Neck venous malformations and their potentially life-threatening complications are rarely reported in the available literature. Cases of aneurysmal or hypo-plastic jugular vein thrombosis associated with systemic embolization have not been frequently reported. We present the case of a 60-year-old male, without any known risk factors for thromboembolic disease, admitted for sudden onset dyspnea. The physical examination was remarkable for a right lateral cervical mass, expanding with Valsalva maneuver. Thoracic CT with contrast established the diagnosis of bilateral pulmonary embolism and raised the suspicion of superior vena cava and right atrial thrombosis. Bedside transthoracic echocardiography confirmed the presence of a large right atrial thrombus, with intermittent protrusion through the tricuspid valve. Systemic thrombolysis with Alteplase was initiated shortly after diagnosis, in parallel with unfractionated heparin, with complete resolution of the intracavitary thrombus documented by echocardiography. The patient showed significant improvement in symptoms and was later started on oral anticoagulation. Computed vascular tomography of the neck was performed before discharge, showing hypoplasia of the left internal jugular vein and aneurismal dilation of the contralateral internal jugular vein, without thrombosis. There were no identifiable systemic causes for thrombosis. Surgical resection of the aneurismal jugular vein was excluded, because of its potential to cause intracranial hypertension. The preferred therapeutic option in this case was long-term oral anticoagulation

Characterization of soft x-ray echo-enabled harmonic generation free-electron laser pulses in the presence of incoherent electron beam energy modulations

Echo-enabled harmonic generation free-electron lasers (EEHG FELs) are promising candidates to produce fully coherent soft x-ray pulses by virtue of efficient high-harmonic frequency up-conversion from ultraviolet lasers. The ultimate spectral limit of EEHG, however, remains unclear, because of the broadening and distortions induced in the output spectrum by residual broadband energy modulations in the electron beam. We present a mathematical description of the impact of incoherent (broadband) energy modulations on the bunching spectrum produced by the microbunching instability through both the accelerator and the EEHG line. The model is in agreement with a systematic experimental characterization of the FERMI EEHG FEL in the photon energy range 130\u2013210 eV. We find that amplification of electron beam energy distortions primarily in the EEHG dispersive sections explains an observed reduction of the FEL spectral brightness proportional to the EEHG harmonic number. Local maxima of the FEL spectral brightness and of the spectral stability are found for a suitable balance of the dispersive sections\u2019 strength and the first seed laser pulse energy. Such characterization provides a benchmark for user experiments and future EEHG implementations designed to reach shorter wavelengths