303. Image registration – precise quality assessment of radiotherapy without necessity of showing corresponding points in simulation and portal images

PurposeEnabling the quality assessment of radiotherapy to be made in daily practice, using the new software tool to analyze the simulation and portal images.MethodIn the registration of the anatomical structures as well as the irradiation fields, the features used as landmarks are the edges. The significant edge fragments must be chosen manually, but without showing any specific corresponding points. Field edges marked with wires in the simulation image are found fully automatically with the original combination of a dedicated line edge detector and a version of hierarchical, combined Hough transform. The registration is guided by the robust accuracy criterion using the modified Hausdorff distance measure. The only parameter of the measure – quantile rank, or share of data used in comparison – is not fixed, but evolves from 1 to 0 during the optimization of the accuracy. This has two advantages. 1: The user can choose the result found for the share corresponding to the actual share of erroneous data in the images, which can be seen only after the results for all the possible ranks are known. 2: The algorithm can avoid the local minima. The registration takes few seconds on a typical PC. The method has been implemented in a software tool which supports the complete process of measurement, and has been tested in clinical triais with positive result.ConclusionsThe modified Hausdorff distance measure with evolving rank is a good and efficient registration accuracy measure for quality assessment of radiotherapy based on the comparison of portal and simulation images

3/Evaluation of set-up deviations during the irradiation of patients suffering from breast cancer treated with two different techniques

PurposeTo present results of patient positioning during routine radiotherapy for patients treated after mastectomy and to compare the inaccuracies in patient set-up for this group of patients and for the patients treated after breast conserving therapy with tangential fields.Methods and materialsIn total, the analysis comprised 56 pairs of portal and simulator films for 14 consecutive patients treated following breast conserving therapy and 98 pairs of portal and simulator films for 20 consecutive patients treated after mastectomy. For the first group the tangential field technique (TF technique) was used, for the second the inverse hockey stick technique (IHS technique). The comparison of the treatment reproducibility obtained for both groups of patients was performed in terms of systematic and random error calculated for the whole groups and by the comparison of cumulative distribution of the length of the displacement vector.ResultsIn the IHS and TF techniques for medial and lateral fields, displacement larger than 5 mm occurred in 28.3%, 15.8% and 25.4% respectively. For the IHS technique, the systematic errors for lateral and cranial-caudal direction were 1.9 and 1.7 mm respectively (1 standard deviation – SD), the random errors for lateral and cranial-caudal direction were 2.0 and 2.5 mm. For the TF technique, the systematic errors for lateral and cranial-caudal direction were 2.6 and 1.3 mm for medial field and 3.7 and 0.7 mm for lateral fields respectively, the random errors for lateral and cranial-caudal direction were 2.2 and 1.0 mm for medial field and 2.9 and 1.1 for lateral field respectively. Rotations were negligible in the HIS technique. For the TF technique the systematic component and random component amounted to about 2.0 degrees (1 SD).ConclusionsBoth the inverse hockey stick and standard tangential techniques showed good reproducibility of patients set-up with respect to cranial-caudal direction. For the TF technique, the accuracy should be improved for the medial field with respect to the ventral-dorsal direction

On an Asymptotic Series of Ramanujan

An asymptotic series in Ramanujan's second notebook (Entry 10, Chapter 3) is concerned with the behavior of the expected value of $\phi(X)$ for large $\lambda$ where $X$ is a Poisson random variable with mean $\lambda$ and $\phi$ is a function satisfying certain growth conditions. We generalize this by studying the asymptotics of the expected value of $\phi(X)$ when the distribution of $X$ belongs to a suitable family indexed by a convolution parameter. Examples include the problem of inverse moments for distribution families such as the binomial or the negative binomial.Comment: To appear, Ramanujan

25. Assessment of the accuracy of radiotherapy by digital superposition of portal and rference images

Teleradiotherapy imposes the requirement of high accuracy in reference to its medical as well as technical aspects. Close adherence to the geometrical parameters set up in therapy planning is vital. The current location of the irradiation field and anatomical structures can be recorded in the portal image acquired during the therapy course. Assessment of the treatment accuracy consists in registration (overlaying) of the reference and the portal image to compare the layout of anatomical structures and the irradiation field. Edges of the compared features are difficult to find in the portal image, which is inherently of low contrast. Hence, not all the edges present in the reference image can be found in the portal one, and the comparison of geometries in these images is difficult and time-consuming. There exists a need for a tool that could support and objectify this process.At present the accuracy assessment is done manually by an experienced observer. As a rule, this tedious procedure is not performed routinely. The wide literature on image registration refers to portal images made with beams generated in accelerators rather than with the cobalt apparata. In Poland more than a half of patients are treated with cobalt. There are numerous references to image registration methods tailored for finding the fitting and non-fitting fragments of the compared edges. The majority of these methods lack generality.The methodology to be presented is general and requires little user intervention.•Features to be matched: edges of selected anatomical structures, irradiation field and shields, as seen in scanned images.•Edge detector: zero-second-derivative with scale fitted to noise and scale of edges, separately in portal and reference images.•Geometrical transformation: affine (2 translations, rotation, 2 scalings – along two coordinate axes).•Measure of fitting accuracy: modified Hausdorff distance measure – robust method based on voting. Parts of the contours that do not fit the general tendency are rejected. This is vital if portal images made with cobalt apparata are analysed.•Optimisation method for finding the best transformation: maximum gradient (chamfer matching).•Final fit can be calculated with le least squares method for only those pixels which were classified as fitting.•Speed-ups: hierarchical method (pyramid of resolutions); in some cases: pre-calculated virtual transformations.•Automatic classification of edges as belonging to anatomic structures, irradiation field or shields is possible.•Experiments with enhancing the contrast of portal images using the optical system transfer function concept.The software tool will be presented which makes it possible to correct the therapeutic system geometry or the location of the patient. Full control of the physician over the measurement process will be maintained, according to the requirement of human decision-making in the therapeutical process. The registration (overlaying) of a portal and a reference image is visualised for verification. Manual corrections of the result will be possible in the final version of the program.Acknowledgement The work is supported by the Committee for Scientific Research within the grant no. KBN 4 P05B 064 18

DNA methylation in human gastric epithelial cells defines regional identity without restricting lineage plasticity

BACKGROUND: Epigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronic Helicobacter pylori infections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail. RESULTS: Here, we establish gastric mucosa derived primary cell cultures as a reliable source of native human epithelium. We describe the DNA methylation landscape across the phenotypically different regions of the healthy human stomach, i.e., antrum, corpus, fundus together with the corresponding transcriptomes. We show that stable regional DNA methylation differences translate to a limited extent into regulation of the transcriptomic phenotype, indicating a largely permissive epigenetic regulation. We identify a small number of transcription factors with novel region-specific activity and likely epigenetic impact in the stomach, including GATA4, IRX5, IRX2, PDX1 and CDX2. Detailed analysis of the Wnt pathway reveals differential regulation along the craniocaudal axis, which involves non-canonical Wnt signaling in determining cell fate in the proximal stomach. By extending our analysis to pre-neoplastic lesions and gastric cancers, we conclude that epigenetic dysregulation characterizes intestinal metaplasia as a founding basis for functional changes in gastric cancer. We present insights into the dynamics of DNA methylation across anatomical regions of the healthy stomach and patterns of its change in disease. Finally, our study provides a well-defined resource of regional stomach transcription and epigenetics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01406-4

Evaluating the validity and applicable domain of the toxic load model: Impact of concentration vs. time profile on inhalation lethality of hydrogen cyanide

The ten Berge model (or ‘‘toxic load’’ model) is often used to estimate the acute toxicity for varying combinations of inhaled concentration and duration. Expressed as Cn X t = toxic load (TL), TLs are assumed constant for various combinations of concentration (C) and time (t). Experimental data in a recent acute inhalation study of rats exposed to time-varying concentrations of hydrogen cyanide (HCN) supported the validity of the toxic load model except under very brief, discontinuous, high concentration exposures. In the present investigation, experiments were conducted to extend the evaluation of the applicable domain of the model for acute lethality of HCN in the rat (cumulative exposure range of 2900–11,000 ppm min). The lethality of HCN over very short (\u3c5 min) durations of high concentrations did not conform to the toxic load model. A value of n = 1.57 was determined for uninterrupted exposures P5 min. For 30-min exposures, the presence or absence of a gap between two exposure pulses of different concentrations, the relative duration, relative height, and the ordering of the pulses (low then high, vs. high then low) did not appear to have a meaningful impact on the toxic load required for median lethality

Charting the Chemical and Mechanistic Scope of Light-Triggered Protein Ligation

The creation of discrete, covalent bonds between a protein and a functional molecule like a drug, fluorophore, or radiolabeled complex is essential for making state-of-the-art tools that find applications in basic science and clinical medicine. Photochemistry offers a unique set of reactive groups that hold potential for the synthesis of protein conjugates. Previous studies have demonstrated that photoactivatable desferrioxamine B (DFO) derivatives featuring a para-substituted aryl azide ($ArN_3$) can be used to produce viable zirconium-89-radiolabeled monoclonal antibodies ($^{89}Zr-mAbs$) for applications in noninvasive diagnostic positron emission tomography (PET) imaging of cancers. Here, we report on the synthesis, $^{89}Zr$-radiochemistry, and light-triggered photoradiosynthesis of $^{89}Zr$-labeled human serum albumin (HSA) using a series of 14 different photoactivatable DFO derivatives. The photoactive groups explore a range of substituted, and isomeric $ArN_3$ reagents, as well as derivatives of benzophenone, a para-substituted trifluoromethyl phenyl diazirine, and a tetrazole species. For the compounds studied, efficient photochemical activation occurs inside the UVA-to-visible region of the electromagnetic spectrum (∼365–450 nm) and the photochemical reactions with HSA in water were complete within 15 min under ambient conditions. Under standardized experimental conditions, photoradiosynthesis with compounds 1–14 produced the corresponding $^{89}ZrDFO-PEG_{3}-HSA$ conjugates with decay-corrected isolated radiochemical yields between 18.1 ± 1.8% and 62.3 ± 3.6%. Extensive density functional theory (DFT) calculations were used to explore the reaction mechanisms and chemoselectivity of the light-induced bimolecular conjugation of compounds 1–14 to protein. The photoactivatable DFO-derivatives operate by at least five distinct mechanisms, each producing a different type of bioconjugate bond. Overall, the experimental and computational work presented here confirms that photochemistry is a viable option for making diverse, functionalized protein conjugates