Reducing MRI-guided radiotherapy planning and delivery times via efficient leaf sequencing and segment shape optimization algorithms.

Objective.Extended treatment session times are an operational limitation in magnetic resonance imaging guided adaptive radiotherapy (MRIgRT). In this study a novel leaf sequencing algorithm called optimal fluence levels (OFL) and an optimization algorithm called pseudo gradient descent (PGD) are evaluated with respect to plan quality, beam complexity, and the ability to reduce treatment session times on the Elekta Unity MRIgRT system.Approach.Ten total patients were evaluated on this Institutional Review Board approved study: three with prostate cancer, three with oligometastases, two with pancreatic cancer, and two with liver cancer. Plans were generated using the clinical Monaco Hyperion optimizer and leaf sequencer and then re-optimized using OFL and PGD (OFL + PGD) while holding all IMRT constraints and planning parameters constant. All plans were normalized to ensure 95% of the PTV received the prescription dose. A paired t-test was used to evaluate statistical significance.Main Results.Plan quality in terms of dosimetric OAR sparing was found to be equivalent between the OFL + PGD and conventional Monaco Hyperion optimizer plans. The OFL + PGD plans had a reduction in optimization time of 51.4% ± 5.0% (p = 0.002) and reduction in treatment delivery time of 10.6% ± 7.5% (p = 0.005). OFL + PGD generated plans had on average 13.2% ± 12.6% fewer multi-leaf collimator (MLC) segments (p = 0.009) and 0.1 ± 0.1 lower plan averaged beam modulation (PM) (p = 0.004) relative to the Monaco Hyperion plans.Significance.The OFL + PGD algorithms more quickly generate Unity treatment plans that are faster to deliver than with the conventional approach and without compromising dosimetric plan quality. This is likely due to a delivery complexity reduction enabled by OFL + PGD relative to the Monaco Hyperion plans.

Automatic reconstruction of the delivered dose of the day using MR-linac treatment log files and online MR imaging.

BACKGROUND AND PURPOSE: Anatomical changes during external beam radiotherapy prevent the accurate delivery of the intended dose distribution. Resolving the delivered dose, which is currently unknown, is crucial to link radiotherapy doses to clinical outcomes and ultimately improve the standard of care. MATERIAL AND METHODS: In this study, we present a dose reconstruction workflow based on data routinely acquired during MR-guided radiotherapy. It employs 3D MR images, 2D cine MR images and treatment machine log files to calculate the delivered dose taking intrafractional motion into account. The developed pipeline was used to measure anatomical changes and assess their dosimetric impact in 89 prostate radiotherapy fractions delivered with a 1.5 T MR-linac at our institute. RESULTS: Over the course of radiation delivery, the CTV shifted 0.6 mm ± 2.1 mm posteriorly and 1.3 mm ± 1.5 mm inferiorly. When extrapolating the dose changes in each case to 20 fractions, the mean clinical target volume D98% and clinical target volume D50% dose-volume metrics decreased by 1.1 Gy ± 1.6 Gy and 0.1 Gy ± 0.2 Gy, respectively. Bladder D3% did not change (0.0 Gy ± 1.2 Gy), while rectum D3% decreased by 1.0 Gy ± 2.0 Gy. Although anatomical changes and their dosimetric impact were small in the majority of cases, large intrafractional motion caused the delivered dose to substantially deviate from the intended plan in some fractions. CONCLUSIONS: The presented end-to-end workflow is able to reliably, non-invasively and automatically reconstruct the delivered prostate radiotherapy dose by processing MR-linac treatment log files and online MR images. In the future, we envision this workflow to be adapted to other cancer sites and ultimately to enter widespread clinical use.

Sequence analysis of the medium and small RNAs of impatiens necrotic spot virus reveals segment reassortment but not recombination.

The complete sequence of the medium (M) and small (S) RNA genome segments were determined for twelve isolates of impatiens necrotic spot virus from eight plant species. The M- and S-RNAs of these isolates shared 97-99% and 93-98% nucleotide sequence identity, respectively, with the corresponding full-length sequences available in public databases. Phylogenetic analysis based on the M- or S-RNA sequences showed incongruence in the phylogenetic position of some isolates, suggesting intraspecies segment reassortment. The lack of phylogenetic discordance in individual and concatenated sequences of individual genes encoded by M- or S-RNAs suggests that segment reassortment rather than recombination is driving evolution of these INSV isolates.

An efficient and high fidelity method for amplification, cloning and sequencing of complete tospovirus genomic RNA segments.

Tospoviruses (genus Tospovirus, family Bunyaviridae) are responsible for major losses in an extensive range of crops worldwide. New species of these single-stranded, ambisense RNA viruses regularly emerge and have been shown to maintain heterogeneous populations with individual isolates having quite variable biological and virulence characteristics. Most tospovirus phylogenetic studies have focused on analysis of a single gene, most often the nucleocapsid protein gene. Complete genomic RNA segment amplification as a single fragment would facilitate more detailed analyses of genome-wide sequence variability, but obtaining such sequences for a large number of tospovirus isolates using traditional methods of amplification and cloning of small overlapping fragments is tedious, time consuming and expensive. In this study, protocols were optimized to amplify, clone and sequence full-length M- and S-RNA genome segments of Tomato spotted wilt virus and Impatiens necrotic spot virus. The strategy presented here is straightforward, scalable and offers several advantages over the previously commonplace and overlapping amplicon-based approach. Use of whole genome segments, instead of individual gene sequences or defined portions of genome segments, will facilitate a better understanding of the underlying molecular diversity of tospoviruses in mixed infections.

Emergence of Groundnut ringspot virus and Tomato chlorotic spot virus in Vegetables in Florida and the Southeastern United States.

Groundnut ringspot virus (GRSV) and Tomato chlorotic spot virus (TCSV) are two emerging tospoviruses in Florida. In a survey of the southeastern United States, GRSV and TCSV were frequently detected in solanaceous crops and weeds with tospovirus-like symptoms in south Florida, and occurred sympatrically with Tomato spotted wilt virus (TSWV) in tomato and pepper in south Florida. TSWV was the only tospovirus detected in other survey locations, with the exceptions of GRSV from tomato (Solanum lycopersicum) in South Carolina and New York, both of which are first reports. Impatiens (Impatiens walleriana) and lettuce (Lactuca sativa) were the only non-solanaceous GRSV and/or TCSV hosts identified in experimental host range studies. Little genetic diversity was observed in GRSV and TCSV sequences, likely due to the recent introductions of both viruses. All GRSV isolates characterized were reassortants with the TCSV M RNA. In laboratory transmission studies, Frankliniella schultzei was a more efficient vector of GRSV than F. occidentalis. TCSV was acquired more efficiently than GRSV by F. occidentalis but upon acquisition, transmission frequencies were similar. Further spread of GRSV and TCSV in the United States is possible and detection of mixed infections highlights the opportunity for additional reassortment of tospovirus genomic RNAs.