Considerations for Upright Particle Therapy Patient Positioning and Associated Image Guidance

Particle therapy is a rapidly growing field in cancer therapy. Worldwide, over 100 centers are in operation, and more are currently in construction phase. The interest in particle therapy is founded in the superior target dose conformity and healthy tissue sparing achievable through the particles’ inverse depth dose profile. This physical advantage is, however, opposed by increased complexity and cost of particle therapy facilities. Particle therapy, especially with heavier ions, requires large and costly equipment to accelerate the particles to the desired treatment energy and steer the beam to the patient. A significant portion of the cost for a treatment facility is attributed to the gantry, used to enable different beam angles around the patient for optimal healthy tissue sparing. Instead of a gantry, a rotating chair positioning system paired with a fixed horizontal beam line presents a suitable cost-efficient alternative. Chair systems have been used already at the advent of particle therapy, but were soon dismissed due to increased setup uncertainty associated with the upright position stemming from the lack of dedicated image guidance systems. Recently, treatment chairs gained renewed interest due to the improvement in beam delivery, commercial availability of vertical patient CT imaging and improved image guidance systems to mitigate the problem of anatomical motion in seated treatments. In this review, economical and clinical reasons for an upright patient positioning system are discussed. Existing designs targeted for particle therapy are reviewed, and conclusions are drawn on the design and construction of chair systems and associated image guidance. Finally, the different aspects from literature are channeled into recommendations for potential upright treatment layouts, both for retrofitting and new facilities

Considerations for Upright Particle Therapy Patient Positioning and Associated Image Guidance

Particle therapy is a rapidly growing field in cancer therapy. Worldwide, over 100 centers are in operation, and more are currently in construction phase. The interest in particle therapy is founded in the superior target dose conformity and healthy tissue sparing achievable through the particles’ inverse depth dose profile. This physical advantage is, however, opposed by increased complexity and cost of particle therapy facilities. Particle therapy, especially with heavier ions, requires large and costly equipment to accelerate the particles to the desired treatment energy and steer the beam to the patient. A significant portion of the cost for a treatment facility is attributed to the gantry, used to enable different beam angles around the patient for optimal healthy tissue sparing. Instead of a gantry, a rotating chair positioning system paired with a fixed horizontal beam line presents a suitable cost-efficient alternative. Chair systems have been used already at the advent of particle therapy, but were soon dismissed due to increased setup uncertainty associated with the upright position stemming from the lack of dedicated image guidance systems. Recently, treatment chairs gained renewed interest due to the improvement in beam delivery, commercial availability of vertical patient CT imaging and improved image guidance systems to mitigate the problem of anatomical motion in seated treatments. In this review, economical and clinical reasons for an upright patient positioning system are discussed. Existing designs targeted for particle therapy are reviewed, and conclusions are drawn on the design and construction of chair systems and associated image guidance. Finally, the different aspects from literature are channeled into recommendations for potential upright treatment layouts, both for retrofitting and new facilities

A phosphoinositide hub connects CLE peptide signaling and polar auxin efflux regulation

Auxin efflux through plasma-membrane-integral PIN-FORMED (PIN) carriers is essential for plant tissue organization and tightly regulated. For instance, a molecular rheostat critically controls PIN-mediated auxin transport in developing protophloem sieve elements of Arabidopsis roots. Plasma-membrane-association of the rheostat proteins, BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX), is reinforced by interaction with PHOSPHATIDYLINOSITOL-4-PHOSPHATE-5-KINASE (PIP5K). Genetic evidence suggests that BRX dampens autocrine signaling of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 45 (CLE45) peptide via its receptor BARELY ANY MERISTEM 3 (BAM3). How excess CLE45-BAM3 signaling interferes with protophloem development and whether it does so directly or indirectly remains unclear. Here we show that rheostat polarity is independent of PIN polarity, but interdependent with PIP5K. Catalytically inactive PIP5K confers rheostat polarity without reinforcing its localization, revealing a possible PIP5K scaffolding function. Moreover, PIP5K and PAX cooperatively control local PIN abundance. We further find that CLE45-BAM3 signaling branches via RLCK-VII/PBS1-LIKE (PBL) cytoplasmic kinases to destabilize rheostat localization. Our data thus reveal antagonism between CLE45-BAM3-PBL signaling and PIP5K that converges on auxin efflux regulation through dynamic control of PAX polarity. Because second-site bam3 mutation suppresses root as well as shoot phenotypes of pip5k mutants, CLE peptide signaling likely modulates phosphoinositide-dependent processes in various developmental contexts

Investigating Slit-Collimator-Produced Carbon Ion Minibeams with High-Resolution CMOS Sensors

Particle minibeam therapy has demonstrated the potential for better healthy tissue sparing due to spatial fractionation of the delivered dose. Especially for heavy ions, the spatial fractionation could enhance the already favorable differential biological effectiveness at the target and the entrance region. Moreover, spatial fractionation could even be a viable option for bringing ions heavier than carbon back into patient application. To understand the effect of minibeam therapy, however, requires careful conduction of pre-clinical experiments, for which precise knowledge of the minibeam characteristics is crucial. This work introduces the use of high-spatial-resolution CMOS sensors to characterize collimator-produced carbon ion minibeams in terms of lateral fluence distribution, secondary fragments, track-averaged linear energy transfer distribution, and collimator alignment. Additional simulations were performed to further analyze the parameter space of the carbon ion minibeams in terms of beam characteristics, collimator positioning, and collimator manufacturing accuracy. Finally, a new concept for reducing the neutron dose to the patient by means of an additional neutron shield added to the collimator setup is proposed and validated in simulation. The carbon ion minibeam collimator characterized in this work is used in ongoing pre-clinical experiments on heavy ion minibeam therapy at the GSI

Range margin reduction in carbon ion therapy: potential benefits of using radioactive ion beams

Radiotherapy with heavy ions, in particular, 12C beams, is one of the most advanced forms of cancer treatment. Sharp dose gradients and high biological effectiveness in the target region make them an ideal tool to treat deep-seated and radioresistant tumors, however, at the same time, sensitive to small errors in the range prediction. Safety margins are added to the tumor volume to mitigate these uncertainties and ensure its uniform coverage, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully exploit the benefits of a sharp Bragg peak, a large effort is put into establishing precise range verification methods for the so-called image-guided radiotherapy. Despite positron emission tomography being widely in use for this purpose in 12C ion therapy, the low count rates, biological washout, and broad shape of the activity distribution still limit its precision to a few millimeters. Instead, radioactive beams used directly for treatment would yield an improved signal and a closer match with the dose fall-off, potentially enabling precise in vivo beam range monitoring. We have performed a treatment planning study to estimate the possible impact of the reduced range uncertainties, enabled by radioactive 11C beams treatments, on sparing critical organs in the tumor proximity. We demonstrate that (i) annihilation maps for 11C ions can in principle reflect even millimeter shifts in dose distributions in the patient, (ii) outcomes of treatment planning with 11C beams are significantly improved in terms of meeting the constraints for the organs at risk compared to 12C plans, and (iii) less severe toxicities for serial and parallel critical organs can be expected following 11C treatment with reduced range uncertainties, compared to 12C treatments

Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL), DSM-5 update: translation into Brazilian Portuguese

Brazilian governmental research funding agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Brazilian governmental research funding agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Brazilian governmental research funding agency Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)ShireNovartisEli LillyJanssen-CilagUniv Fed Rio Grande do Sul, Fac Med, Dept Psiquiatria, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Fac Med, Dept Pediat, Porto Alegre, RS, BrazilUniv Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilPontifica Univ Catolica Rio Grande do Sul, Dev Cognit Neurosci Res Grp GNCD, Porto Alegre, RS, BrazilInst Bairral Psiquiatria, Ctr Integrado Desenvolvimento Infancia & Adolesce, Itapira, BrazilUniv Fed Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilWeb of Scienc