Technical note: Characterization of a multi-point scintillation dosimetry research platform for a low-field MR-Linac.

BACKGROUND: MRI-guided radiation therapy (MRgRT) requires unique quality assurance equipment to address MR-compatibility needs, minimize electron return effect, handle complex dose distributions, and evaluate real-time dosimetry for gating. Plastic scintillation detectors (PSDs) are an attractive option to address these needs. PURPOSE: To perform a comprehensive characterization of a multi-probe PSD system in a low-field 0.35 T MR-linac, including detector response assessment and gating performance. METHODS: A four-channel PSD system (HYPERSCINT RP-200) was assembled. A single channel was used to evaluate repeatability, percent depth dose (PDD), detector response as a function of orientation with respect to the magnetic field, and intersession variability. All four channels were used to evaluate repeatability, linearity, and output factors. The four PSDs were integrated into an MR-compatible motion phantom at isocenter and in gradient regions. Experiments were conducted to evaluate gating performance and tracking efficacy. RESULTS: For repeatability, the maximum standard deviation of repeated measurements was 0.13% (single PSD). Comparing the PSD to reference data, PDD had a maximum difference of 1.12% (10 cm depth, 6.64 × 6.64 cm2). Percent differences for rotated detector setups were negligible (< 0.3%). All four PSDs demonstrated linear response over 10-1000 MU delivered and the maximum percent difference between the baseline and measured output factors was 0.78% (2.49 × 2.49 cm2). Gating experiments had 400 cGy delivered to isocenter with < 0.8 cGy variation for central axis measures and < 0.7 cGy for the gradient sampled region. Real-time dosimetry measurements captured spurious beam-on incidents that correlated to tracking algorithm inaccuracies and highlighted gating parameter impact on delivery efficiency. CONCLUSIONS: Characterization of the multi-point PSD dosimetry system in a 0.35 T MR-linac demonstrated reliability in a low-field MR-Linac setting, with high repeatability, linearity, small intersession variability, and similarity to baseline data for PDD and output factors. Time-resolved, multi-point dosimetry also showed considerable promise for gated MR-Linac applications.

A lesion-mimic mutant of Catharanthus roseus accumulates the opioid agonist, akuammicine.

Catharanthus roseus is a medicinal plant that produces an abundance of monoterpenoid indole alkaloids (MIAs), notably including the anticancer compounds vinblastine and vincristine. While the canonical pathway leading to these drugs has been resolved, the regulatory and catalytic mechanisms controlling many lateral branches of MIA biosynthesis remain largely unknown. Here, we describe an ethyl methanesulfonate (EMS) C. roseus mutant (M2-117523) that accumulates high levels of MIAs. The mutant exhibited stunted growth, partially chlorotic leaves, with deficiencies in chlorophyll biosynthesis, and a lesion-mimic phenotype. The lesions were sporadic and spontaneous, appearing after the first true bifoliate and continuing throughout development. The lesions are also the site of high concentrations of akuammicine, a minor constituent of wild type C. roseus leaves. In addition to akuammicine, the lesions were enriched in 25 other MIAs, resulting, in part, from a higher metabolic flux through the pathway. The unique metabolic shift was associated with significant upregulation of biosynthetic and regulatory genes involved in the MIA pathway, including the transcription factors WRKY1, CrMYC2, and ORCA2, and the biosynthetic genes STR, GO, and Redox1. Following the lesion-mimic mutant (LMM) phenotype, the accumulation of akuammicine is jasmonate (JA)-inducible, suggesting a role in plant defence response. Akuammicine is medicinally significant, as a weak opioid agonist, with a preference for the κ-opioid receptor, and a potential anti-diabetic. Further study of akuammicine biosynthesis and regulation can guide plant and heterologous engineering for medicinal uses.