Deep learning-based dose prediction for magnetic resonance-guided prostate radiotherapy.

Background: Daily adaptive radiotherapy, as performed with the Elekta Unity MR-Linac, requires choosing between different adaptation methods, namely ATP (Adapt to Position) and ATS (Adapt to Shape), where the latter requires daily re-contouring to obtain a dose plan tailored to the daily anatomy. These steps are inherently resource-intensive, and quickly predicting the dose distribution and the dosimetric evaluation criteria while the patient is on the table could facilitate a fast selection of adaptation method and decrease the treatment times.

Purpose: In this work, we aimed to develop a deep-learning-based dose-prediction pipeline for prostate MR-Linac treatments.

The Quality Assurance of a 1.5 T MR-Linac.

The recent introduction of a commercial 1.5 T MR-linac system has considerably improved the image quality of the patient acquired in the treatment unit as well as enabling online adaptive radiation therapy (oART) treatment strategies. Quality Assurance (QA) of this new technology requires new methodology that allows for the high field MR in a linac environment.

Enantioselective conjugate addition to nitroolefins catalysed by helical peptides with a single remote stereogenic centre.

Two short pentapeptides rich in α-aminoisobutyric acid (Aib) residues have been shown to act as enantioselective organocatalysts for the conjugate addition of nucleophiles to nitroolefins. An L-alanine terminated peptide, (Aib)(L-Ala)NHBu, which has neither functionalised sidechains nor a highly designed reactive site, used an exposed N-terminal primary amine and the amide bonds of the backbone to mediate catalysis. Folding of this peptide into a 3 helical structure was observed by crystallography.

Anion-Dependent Hydrogen-Bond Polarity Switching in Ethylene-bridged Urea Oligomers.

The reversible coordination of anions to an N,N'-disubstituted 3,5-bis(trifluoromethyl)phenylurea located at a terminus of a linear chain of ethylene-bridged hydrogen-bonded ureas triggers a cascade of conformational changes. A series of hydrogen-bond polarity reversals propagates along the oligomer, leading to a global switch of its hydrogen-bond directionality. The induced polarity switch, transmitted through four reversible urea groups, results in a change in emission and excitation wavelengths of a fluorophore located at the opposite terminus of the oligomer.

Switching imidazole reactivity by dynamic control of tautomer state in an allosteric foldamer.

Molecular biology achieves control over complex reaction networks by means of molecular systems that translate a chemical input (such as ligand binding) into an orthogonal chemical output (such as acylation or phosphorylation). We present an artificial molecular translation device that converts a chemical input - the presence of chloride ions - into an unrelated chemical output: modulation of the reactivity of an imidazole moiety, both as a Brønsted base and as a nucleophile. The modulation of reactivity operates through the allosteric remote control of imidazole tautomer states.

Dosimetric validation of the couch and coil model for high-field MR-linac treatment planning.

Purpose: The precision of the dose delivery in radiation therapy with high-field MR-linacs is challenging due to the substantial variation in the beam attenuation of the patient positioning system (PPS) (the couch and coils) as a function of the gantry angle. This work aimed to compare the attenuation of two PPSs located at two different MR-linac sites through measurements and calculations in the treatment planning system (TPS).

Methods: Attenuation measurements were performed at every 1° gantry angle at the two sites with a cylindrical water phantom with a Farmer chamber inserted along the rotational axis of the phantom.

Supramolecular interactions between ethylene-bridged oligoureas: nanorings and chains formed by cooperative positive allostery.

Ethylene-bridged oligoureas are dynamic foldamers in which the polarity of a coherent chain of intramolecular hydrogen bonds may be controlled by intra- or intermolecular interactions with hydrogen-bond donors or acceptors. In this paper, we describe the way that supramolecular interactions between ethylene-bridged oligoureas bearing a 3,5-bis(trifluoromethyl)phenylurea (BTMP) terminus leads to higher-order structures both in the crystalline state and in solution. The oligoureas self-assemble by head-to-tail hydrogen bonding interactions to form either supramolecular 'nanorings' with cyclic hydrogen bond chain directionality, or supramolecular helical chains of hydrogen bonds.

Adaptive dose painting for prostate cancer.

Purpose: Dose painting (DP) is a radiation therapy (RT) strategy for patients with heterogeneous tumors delivering higher dose to radiation resistant regions and less to sensitive ones, thus aiming to maximize tumor control with limited side effects. The success of DP treatments is influenced by the spatial accuracy in dose delivery. Adaptive RT (ART) workflows can reduce the overall geometric dose delivery uncertainty.

Patient specific deep learning based segmentation for magnetic resonance guided prostate radiotherapy.

Background And Purpose: Treatments on combined Magnetic Resonance (MR) scanners and Linear Accelerators (Linacs) for radiotherapy, called MR-Linacs, often require daily contouring. Currently, deformable image registration (DIR) algorithms propagate contours from reference scans, however large shape and size changes can be troublesome. Artificial neural network (ANN) based contouring may alleviate this issue, however generally requires large datasets for training.

α-Amino-iso-Butyric Acid Foldamers Terminated with Rhodium(I) N-Heterocyclic Carbene Catalysts.

To investigate how remotely induced changes in ligand folding might affect catalysis by organometallic complexes, dynamic α-amino-iso-butyric acid (Aib) peptide foldamers bearing rhodium(I) N-heterocyclic carbene (NHC) complexes have been synthesized and studied. X-ray crystallography of a foldamer with an N-terminal azide and a C-terminal Rh(NHC)(Cl)(diene) complex showed a racemate with a chiral axis in the Rh(NHC) complex and a distorted 3 helical body. Replacing the azide with either one or two chiral L-α-methylvaline (L-αMeVal) residues gave diastereoisomeric foldamers that each possessed point, helical and axial chirality.

Intrafractional motion models based on principal components in Magnetic Resonance guided prostate radiotherapy.

Background And Purpose: Devices that combine an MR-scanner with a Linac for radiotherapy, referred to as MR-Linac systems, introduce the possibility to acquire high resolution images prior and during treatment. Hence, there is a possibility to acquire individualised learning sets for motion models for each fraction and the construction of intrafractional motion models. We investigated the feasibility for a principal component analysis (PCA) based, intrafractional motion model of the male pelvic region.

A molecular communication channel consisting of a single reversible chain of hydrogen bonds in a conformationally flexible oligomer.

Communication of information through the global switching of conformation in synthetic molecules has hitherto entailed the inversion of chirality. Here, we report a class of oligomer through which information may be communicated through a global reversal of polarity. Ethylene-bridged oligoureas are constitutionally symmetrical, conformationally flexible molecules organized by a single chain of hydrogen bonds running the full length of the oligomer.

End-to-end validation of the geometric dose delivery performance of MR linac adaptive radiotherapy.

The clinical introduction of hybrid magnetic resonance (MR) guided radiotherapy (RT) delivery systems has led to the need to validate the end-to-end dose delivery performance on such machines. In the current study, an MR visible phantom was developed and used to test the spatial deviation between planned and delivered dose at two 1.5 T MR linear accelerator (MR linac) systems, including pre-treatment imaging, dose planning, online imaging, image registration, plan adaptation, and dose delivery.

Probabilistic optimization of dose coverage in radiotherapy.

Background And Purpose: Probabilistic optimization is an alternative to margins for handling geometrical uncertainties in treatment planning of radiotherapy where uncertainties are explicitly incorporated in the optimization. We present a novel probabilistic method based on the same statistical measures as those behind conventional margin based planning.

Material And Methods: (PD) was defined as the dose coverage that a treatment plan meet or exceed to a given probability.

Dose coverage calculation using a statistical shape model-applied to cervical cancer radiotherapy.

A comprehensive methodology for treatment simulation and evaluation of dose coverage probabilities is presented where a population based statistical shape model (SSM) provide samples of fraction specific patient geometry deformations. The learning data consists of vector fields from deformable image registration of repeated imaging giving intra-patient deformations which are mapped to an average patient serving as a common frame of reference. The SSM is created by extracting the most dominating eigenmodes through principal component analysis of the deformations from all patients.

Assessing guideline impact on referral patterns of post-prostatectomy patients to radiation oncologists.

Introduction: Adjuvant radiotherapy (aRT) can improve biochemical progression-free survival in patients with high-risk features (HRF) after radical prostatectomy (RP). Guidelines from Alberta and the Genitourinary Radiation Oncologists of Canada (GUROC) recommend that patients with HRF be referred to radiation oncologists (RO) based on the findings from three randomized, controlled trials (RCT). Our study examines the impact of these recommendations both pre- (2005) and post- (2012) publication of RCT and GUROC guideline establishment.

Fast dose algorithm for generation of dose coverage probability for robustness analysis of fractionated radiotherapy.

A fast algorithm is constructed to facilitate dose calculation for a large number of randomly sampled treatment scenarios, each representing a possible realisation of a full treatment with geometric, fraction specific displacements for an arbitrary number of fractions. The algorithm is applied to construct a dose volume coverage probability map (DVCM) based on dose calculated for several hundred treatment scenarios to enable the probabilistic evaluation of a treatment plan.For each treatment scenario, the algorithm calculates the total dose by perturbing a pre-calculated dose, separately for the primary and scatter dose components, for the nominal conditions.

Dose mapping sensitivity to deformable registration uncertainties in fractionated radiotherapy - applied to prostate proton treatments.

Background: Calculation of accumulated dose in fractionated radiotherapy based on spatial mapping of the dose points generally requires deformable image registration (DIR). The accuracy of the accumulated dose thus depends heavily on the DIR quality. This motivates investigations of how the registration uncertainty influences dose planning objectives and treatment outcome predictions.

Computed CH acidity of biaryl compounds and their deprotonative metalation by using a mixed lithium/zinc-TMP base.

With the aim of synthesizing biaryl compounds, several aromatic iodides were prepared by the deprotonative metalation of methoxybenzenes, 3-substituted naphthalenes, isoquinoline, and methoxypyridines by using a mixed lithium/zinc-TMP (TMP=2,2,6,6-tetramethylpiperidino) base and subsequent iodolysis. The halides thus obtained, as well as commercial compounds, were cross-coupled under palladium catalysis (e.g.

Directed remote aromatic metalations: mechanisms and driving forces.

Directed remote aromatic metalations are useful synthetic transformations allowing for rapid regioselective access to elaborate highly substituted carbocyclic aromatic and heteroaromatic systems. This review unravels the tangle of data reported on directed remote aromatic metalations. Through a careful analysis of critically selected examples, advanced rationalizations of remote metalation regioselectivities are presented.

Mitochondrially targeted α-tocopheryl succinate is antiangiogenic: potential benefit against tumor angiogenesis but caution against wound healing.

Aims: A plausible strategy to reduce tumor progress is the inhibition of angiogenesis. Therefore, agents that efficiently suppress angiogenesis can be used for tumor suppression. We tested the antiangiogenic potential of a mitochondrially targeted analog of α-tocopheryl succinate (MitoVES), a compound with high propensity to induce apoptosis.

Mitochondrial targeting of α-tocopheryl succinate enhances its pro-apoptotic efficacy: a new paradigm for effective cancer therapy.

Mitochondria are emerging as intriguing targets for anti-cancer agents. We tested here a novel approach, whereby the mitochondrially targeted delivery of anti-cancer drugs is enhanced by the addition of a triphenylphosphonium group (TPP(+)). A mitochondrially targeted analog of vitamin E succinate (MitoVES), modified by tagging the parental compound with TPP(+), induced considerably more robust apoptosis in cancer cells with a 1-2 log gain in anti-cancer activity compared to the unmodified counterpart, while maintaining selectivity for malignant cells.