Convolutional LSTM model for cine image prediction of abdominal motion.

Objective.In this study, we tackle the challenge of latency in magnetic resonance linear accelerator (MR-Linac) systems, which compromises target coverage accuracy in gated real-time radiotherapy. Our focus is on enhancing motion prediction precision in abdominal organs to address this issue. We developed a convolutional long short-term memory (convLSTM) model, utilizing 2D cine magnetic resonance (cine-MR) imaging for this purpose.Approach.Our model, featuring a sequence-to-one architecture with six input frames and one output frame, employs structural similarity index measure (SSIM) as loss function. Data was gathered from 17 cine-MRI datasets using the Philips Ingenia MR-sim system and an Elekta Unity MR-Linac equivalent sequence, focusing on regions of interest (ROIs) like the stomach, liver, pancreas, and kidney. The datasets varied in duration from 1 to 10 min.Main results.The study comprised three main phases: hyperparameter optimization, individual training, and transfer learning with or without fine-tuning. Hyperparameters were initially optimized to construct the most effective model. Then, the model was individually applied to each dataset to predict images four frames ahead (1.24-3.28 s). We evaluated the model's performance using metrics such as SSIM, normalized mean square error, normalized correlation coefficient, and peak signal-to-noise ratio, specifically for ROIs with target motion. The average SSIM values achieved were 0.54, 0.64, 0.77, and 0.66 for the stomach, liver, kidney, and pancreas, respectively. In the transfer learning phase with fine-tuning, the model showed improved SSIM values of 0.69 for the liver and 0.78 for the kidney, compared to 0.64 and 0.37 without fine-tuning.Significance. The study's significant contribution is demonstrating the convLSTM model's ability to accurately predict motion for multiple abdominal organs using a Unity-equivalent MR sequence. This advancement is key in mitigating latency issues in MR-Linac radiotherapy, potentially improving the precision and effectiveness of real-time treatment for abdominal cancers.

Development and Qualification of Physiologically Based Pharmacokinetic Models for Drugs With Atypical Distribution Behavior: A Desipramine Case Study.

Desipramine is a secondary tricyclic amine, which is primarily metabolized by cytochrome 2D6. It shows a high volume of distribution (Vss) (10-50 L/kg) due to its high lipophilicity, unspecific phospholipid binding, and lysosomal trapping. The objective of this study was to develop and qualify a physiologically based pharmacokinetic (PBPK) model for desipramine, which accounts for the high Vss of the drug following intravenous and oral administration of doses up to 100 mg. The model also accounts for the extended time to reach maximum concentration after oral dosing due to enterocyte trapping. Once developed and qualified in adults, we characterized the dynamic changes in metabolism and pharmacokinetics of desipramine after birth by scaling the system-specific parameters of the model from adults to pediatrics. The developed modeling strategy provides a prototypical workflow that can also be applied to other drugs with similar properties and a high volume of distribution.

Influence of smokeless tobacco exposure on detoxification status and chromosomal damage in male and female habitues.

In India, a large number of tobacco chewers and masheri users are chronically exposed to tobacco genotoxicants. Detoxification processes involving cellular glutathione (GSH) and glutathione S-transferases (GST) determine the outcome of exposure to environmental mutagens including those present in tobacco. Hence, in this study, GSH levels, GST activity, GSTM1 genotype and cytogenetic damage were determined using lymphocytes from 114 smokeless tobacco habitues and controls. The study groups comprised of male tobacco chewers, female masheri users, and age- and sex-matched controls. Irrespective of the tobacco habit, GSH levels and GST activity were higher in females than in males. In both the groups of habitues, GSH levels were similar to those in controls, while a significant reduction in GST activity was observed in tobacco chewers only. The frequency of cytogenetic alterations was significantly elevated in both the groups of habitues with respect to controls. However, break-type aberrations were more frequent in tobacco chewers while gaps were commonly observed in masheri users. Differences in the nature of chromosomal alterations in the two groups of habitues appeared to be related to variation in total tobacco exposure and gender-related differences in the efficacy of the GSH/GST detoxification system.