Navigator channel adaptation to reconstruct three dimensional heart volumes from two dimensional radiotherapy planning data

BACKGROUND: Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients. METHODS: Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient. RESULTS: The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62). CONCLUSIONS: The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Transcription errors induce proteotoxic stress and shorten cellular lifespan

Transcription errors occur in all living cells; however, it is unknown how these errors affect cellular health. To answer this question, we monitored yeast cells that were genetically engineered to display error-prone transcription. We discovered that these cells suffer from a profound loss in proteostasis, which sensitizes them to the expression of genes that are associated with protein-folding diseases in humans; thus, transcription errors represent a new molecular mechanism by which cells can acquire disease. We further found that the error rate of transcription increases as cells age, suggesting that transcription errors affect proteostasis particularly in aging cells. Accordingly, transcription errors accelerate the aggregation of a peptide that is implicated in Alzheimer’s disease, and shorten the lifespan of cells. These experiments reveal a novel, basic biological process that directly affects cellular health and aging

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation

Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2–5.3) and IL-6 (OR; 95% CI: 2.6; 1.03–6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2–6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3–5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1–3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1–4.2)

Interfraction liver shape variability and impact on GTV position during liver stereotactic radiotherapy using abdominal compression

PURPOSE: For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. METHODS AND MATERIALS: Evaluable patients were treated in a Research Ethics Board–approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCT scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house–developed finite-element model–based deformable registration (MORFEUS). RESULTS: We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left–right (LR), anterior–posterior (AP), and superior–inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left–right, anterior–posterior, and superior–inferior directions, respectively. CONCLUSIONS: Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid liver-to-liver registrations on respiratory sorted CBCT scans were small in most patients (<5 mm)

Navigator channel adaptation to reconstruct three dimensional heart volumes from two dimensional radiotherapy planning data

Abstract Background Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients. Methods Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient. Results The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62). Conclusions The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects