Limited genetic parallels underlie convergent evolution of quantitative pattern variation in mimetic butterflies.

Mimetic systems allow us to address the question of whether the same genes control similar phenotypes in different species. Although widespread parallels have been found for major effect loci, much less is known about genes that control quantitative trait variation. In this study, we identify and compare the loci that control subtle changes in the size and shape of forewing pattern elements in two Heliconius butterfly co-mimics. We use quantitative trait locus (QTL) analysis with a multivariate phenotyping approach to map the variation in red pattern elements across the whole forewing surface of Heliconius erato and Heliconius melpomene. These results are compared with a QTL analysis of univariate trait changes, and show that our resolution for identifying small effect loci is somewhat improved with the multivariate approach, but also that different loci are detected with these different approaches. QTL likely corresponding to the known patterning gene optix were found in both species but otherwise, a remarkably low level of genetic parallelism was found. This lack of similarity indicates that the genetic basis of convergent traits may not be as predictable as assumed from studies that focus solely on Mendelian traits.

Rapid 4D-MRI reconstruction using a deep radial convolutional neural network: Dracula.

BACKGROUND AND PURPOSE: 4D and midposition MRI could inform plan adaptation in lung and abdominal MR-guided radiotherapy. We present deep learning-based solutions to overcome long 4D-MRI reconstruction times while maintaining high image quality and short scan times. METHODS: Two 3D U-net deep convolutional neural networks were trained to accelerate the 4D joint MoCo-HDTV reconstruction. For the first network, gridded and joint MoCo-HDTV-reconstructed 4D-MRI were used as input and target data, respectively, whereas the second network was trained to directly calculate the midposition image. For both networks, input and target data had dimensions of 256 × 256 voxels (2D) and 16 respiratory phases. Deep learning-based MRI were verified against joint MoCo-HDTV-reconstructed MRI using the structural similarity index (SSIM) and the naturalness image quality evaluator (NIQE). Moreover, two experienced observers contoured the gross tumour volume and scored the images in a blinded study. RESULTS: For 12 subjects, previously unseen by the networks, high-quality 4D and midposition MRI (1.25 × 1.25 × 3.3 mm3) were each reconstructed from gridded images in only 28 seconds per subject. Excellent agreement was found between deep-learning-based and joint MoCo-HDTV-reconstructed MRI (average SSIM ≥ 0.96, NIQE scores 7.94 and 5.66). Deep-learning-based 4D-MRI were clinically acceptable for target and organ-at-risk delineation. Tumour positions agreed within 0.7 mm on midposition images. CONCLUSION: Our results suggest that the joint MoCo-HDTV and midposition algorithms can each be approximated by a deep convolutional neural network. This rapid reconstruction of 4D and midposition MRI facilitates online treatment adaptation in thoracic or abdominal MR-guided radiotherapy.

Synthetic 4D-CT of the thorax for treatment plan adaptation on MR-guided radiotherapy systems.

MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors. Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCTD). The second step added spine density information using an atlas of CT and Dixon MRI (sCTDS). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCTDSL). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCTD,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p  = 0.05). Compared to sCTD and sCTDS, planning on sCTDSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCTDSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCTDSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems.

Phenotypic variation in Heliconius erato crosses shows that iridescent structural colour is sex-linked and controlled by multiple genes.

Bright, highly reflective iridescent colours can be seen across nature and are produced by the scattering of light from nanostructures. Heliconius butterflies have been widely studied for their diversity and mimicry of wing colour patterns. Despite iridescence evolving multiple times in this genus, little is known about the genetic basis of the colour and the development of the structures which produce it. Heliconius erato can be found across Central and South America, but only races found in western Ecuador and Colombia have developed blue iridescent colour. Here, we use crosses between iridescent and non-iridescent races of H. erato to study phenotypic variation in the resulting F2 generation. Using measurements of blue colour from photographs, we find that iridescent structural colour is a quantitative trait controlled by multiple genes, with strong evidence for loci on the Z sex chromosome. Iridescence is not linked to the Mendelian colour pattern locus that also segregates in these crosses (controlled by the gene cortex). Small-angle X-ray scattering data show that spacing between longitudinal ridges on the scales, which affects the intensity of the blue reflectance, also varies quantitatively in F2 crosses.

Treating locally advanced lung cancer with a 1.5T MR-Linac - Effects of the magnetic field and irradiation geometry on conventionally fractionated and isotoxic dose-escalated radiotherapy.

PURPOSE: This study investigates the feasibility and potential benefits of radiotherapy with a 1.5T MR-Linac for locally advanced non-small cell lung cancer (LA NSCLC) patients. MATERIAL AND METHODS: Ten patients with LA NSCLC were retrospectively re-planned six times: three treatment plans were created according to a protocol for conventionally fractionated radiotherapy and three treatment plans following guidelines for isotoxic target dose escalation. In each case, two plans were designed for the MR-Linac, either with standard (∼7mm) or reduced (∼3mm) planning target volume (PTV) margins, while one conventional linac plan was created with standard margins. Treatment plan quality was evaluated using dose-volume metrics or by quantifying dose escalation potential. RESULTS: All generated treatment plans fulfilled their respective planning constraints. For conventionally fractionated treatments, MR-Linac plans with standard margins had slightly increased skin dose when compared to conventional linac plans. Using reduced margins alleviated this issue and decreased exposure of several other organs-at-risk (OAR). Reduced margins also enabled increased isotoxic target dose escalation. CONCLUSION: It is feasible to generate treatment plans for LA NSCLC patients on a 1.5T MR-Linac. Margin reduction, facilitated by an envisioned MRI-guided workflow, enables increased OAR sparing and isotoxic target dose escalation for the respective treatment approaches.

Symptomatic Control of Neuroendocrine Tumours with Everolimus.

Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, increases progression-free survival in patients with advanced neuroendocrine tumours. Patients with neuroendocrine tumours and symptomatic carcinoid have inferior health-related quality of life than those without symptoms. We aimed to evaluate the effect of everolimus on symptomatic control of neuroendocrine tumours. Fifteen patients with metastatic neuroendocrine disease pre-treated with depot octreotide received combination everolimus and octreotide (midgut = 8, pancreatic = 3, other = 4). Reasons for initiation of everolimus were progressive disease (PD) by response evaluation criteria in solid tumours (n = 5), worsening syndromic symptomology (n = 5), or both (n = 5). Symptomatic and objective response and toxicity were evaluated using standard criteria. 7/10 patients who were syndromic had improvements in symptomology, with a mean duration of symptom control 13.9 months (range 1-39). All 10 symptomatic patients had non pancreatic neuroendocrine (pNET) primaries, and with everolimus, 6/10 had reduced stool frequency, 3/7 had a reduction of asthenia, and 5/7 had reduced frequency and severity of flushing. Sixty percent of patients experienced any grade toxicities, including the following: 40% grade 1/2 stomatitis, 7% grade 3/4 stomatitis, 20% grade 1/2 rash, 13% diarrhoea, and one case of pneumonitis. In this cohort of 15 patients, we demonstrated that 70% of non pNET individuals with common carcinoid syndrome symptoms resistant to depot octreotide had improvement in these symptoms on institution of everolimus, with meaningful durations of symptom control. Although this data is observational, to our knowledge, this represents the largest analysis of carcinoid syndrome control with combined everolimus and octreotide.