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.

Zonally Magnified Oblique Multislice and Non-Zonally Magnified Oblique Multislice DWI of the Cervical Spinal Cord.

BACKGROUND AND PURPOSE: The zonally magnified oblique multislice EPI (ZOOM-EPI) diffusion-weighted sequence has been visually shown to provide superior MR diffusion image quality compared with the full-FOV single-shot EPI sequence (non-ZOOM-EPI) in the adult cervical spinal cord. The purpose of this study was to examine the diffusion tensor imaging indices in the normal human cervical spinal cord between ZOOMED and non-ZOOMED DTI acquisitions and determine whether DTI values are comparable between direct and indirect age-matched groups. MATERIALS AND METHODS: Fifty-four subjects 23-58 years of age (9 direct age-matched and 45 indirect age-matched) were scanned using a 1.5T scanner. Diffusion tensor indices including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were generated from the DTI dataset. These DTI values were calculated for both ZOOM and non-ZOOM acquisitions and compared at each intervertebral disc level. The variability of the DTI values for ZOOM and non-ZOOM sequences was measured using a coefficient of variation within direct and indirect age-matched controls. RESULTS: The mean diffusivity, axial diffusivity, and radial diffusivity values obtained along the cervical spinal cord in the age-matched controls showed a significant decrease using the ZOOM sequence (P = .05, P = .002, and P < .001). Mean fractional anisotropy showed a significant increase (P = .04) using the ZOOM sequence. The indirect age-matched controls showed a statistically significant increase in fractional anisotropy (P = .03) and a decrease in mean diffusivity (P = .002), axial diffusivity (P < .001), and radial diffusivity (P = .002) using the ZOOM sequence. Less variability has been shown in DTI using the ZOOM sequence compared with the non-ZOOM sequence in both direct and indirect age groups. The ZOOM sequence exhibited higher SNR (SNRZOOM = 22.84 ± 7.59) compared with the non-ZOOM sequence (SNRnon-ZOOM = 19.7 ± 7.05). However, when we used a 2-tailed t test assuming unequal variances, the ZOOM sequence did not demonstrate a statistically significant increase. CONCLUSIONS: ZOOM DTI acquisition methods provide superior image quality and precision over non-ZOOM techniques and are recommended over conventional full-FOV single-shot EPI DTI for clinical applications in cervical spinal cord imaging.

The use of uterotonic drugs during caesarean section.

The administration of oxytocic drugs during caesarean section is an important intervention to prevent uterine atony or treat established postpartum haemorrhage. Considerable past and current research has shown that these agents have a narrow therapeutic range. A detailed knowledge by anaesthetists of optimal doses and side effects is therefore required. Oxytocin remains the first line agent. In view of receptor desensitisation, second line agents may be required, namely ergot alkaloids and prostaglandins. This review examines the adverse haemodynamic and side effects, and methods for their limitation. An approach to dosing and choices of agent for the limitation of postpartum haemorrhage is suggested.

Mechanism of muscle glycogen autoregulation in humans.

To examine the mechanism by which muscle glycogen limits its own synthesis, muscle glycogen and glucose 6-phosphate (G-6-P) concentrations were measured in seven healthy volunteers during a euglycemic ( approximately 5.5 mM)-hyperinsulinemic ( approximately 450 pM) clamp using (13)C/(31)P nuclear magnetic resonance spectroscopy before and after a muscle glycogen loading protocol. Rates of glycogen synthase (V(syn)) and phosphorylase (V(phos)) flux were estimated during a [1-(13)C]glucose (pulse)-unlabeled glucose (chase) infusion. The muscle glycogen loading protocol resulted in a 65% increase in muscle glycogen content that was associated with a twofold increase in fasting plasma lactate concentrations (P < 0.05 vs. basal) and an approximately 30% decrease in plasma free fatty acid concentrations (P < 0.001 vs. basal). Muscle glycogen loading resulted in an approximately 30% decrease in the insulin-stimulated rate of net muscle glycogen synthesis (P < 0.05 vs. basal), which was associated with a twofold increase in intramuscular G-6-P concentration (P < 0.05 vs. basal). Muscle glycogen loading also resulted in an approximately 30% increase in whole body glucose oxidation rates (P < 0.05 vs. basal), whereas there was no effect on insulin-stimulated rates of whole body glucose uptake ( approximately 10.5 mg. kg body wt(-1). min(-1) for both clamps) or glycogen turnover (V(syn)/V(phos) was approximately 23% for both clamps). In conclusion, these data are consistent with the hypothesis that glycogen limits its own synthesis through feedback inhibition of glycogen synthase activity, as reflected by an accumulation of intramuscular G-6-P, which is then shunted into aerobic and anaerobic glycolysis.

Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes.

BACKGROUND: Insulin resistance, a major factor in the pathogenesis of type 2 diabetes mellitus, is due mostly to decreased stimulation of glycogen synthesis in muscle by insulin. The primary rate-controlling step responsible for the decrease in muscle glycogen synthesis is not known, although hexokinase activity and glucose transport have been implicated. METHODS: We used a novel nuclear magnetic resonance approach with carbon-13 and phosphorus-31 to measure intramuscular glucose, glucose-6-phosphate, and glycogen concentrations under hyperglycemic conditions (plasma glucose concentration, approximately 180 mg per deciliter [10 mmol per liter]) and hyperinsulinemic conditions in six patients with type 2 diabetes and seven normal subjects. In vivo microdialysis of muscle tissue was used to determine the gradient between plasma and interstitial-fluid glucose concentrations, and open-flow microperfusion was used to determine the concentrations of insulin in interstitial fluid. RESULTS: The time course and concentration of insulin in interstitial fluid were similar in the patients with diabetes and the normal subjects. The rates of whole-body glucose metabolism and muscle glycogen synthesis and the glucose-6-phosphate concentrations in muscle were approximately 80 percent lower in the patients with diabetes than in the normal subjects under conditions of matched plasma insulin concentrations. The mean (+/-SD) intracellular glucose concentration was 2.0+/-8.2 mg per deciliter (0.11+/-0.46 mmol per liter) in the normal subjects. In the patients with diabetes, the intracellular glucose concentration was 4.3+/-4.9 mg per deciliter (0.24+/-0.27 mmol per liter), a value that was 1/25 of what it would be if hexokinase were the rate-controlling enzyme in glucose metabolism. CONCLUSIONS: Impaired insulin-stimulated glucose transport is responsible for the reduced rate of insulin-stimulated muscle glycogen synthesis in patients with type 2 diabetes mellitus.

Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.

Recent muscle biopsy studies have shown a relation between intramuscular lipid content and insulin resistance. The aim of this study was to test this relation in humans by using a novel proton nuclear magnetic resonance (1H NMR) spectroscopy technique, which enables non-invasive and rapid (approximately 45 min) determination of intramyocellular lipid (IMCL) content. Normal weight non-diabetic adults (n = 23, age 29+/-2 years. BMI = 24.1+/-0.5 kg/m2) were studied using cross-sectional analysis. Insulin sensitivity was assessed by a 2-h hyperinsulinaemic (approximately 450 pmol/l)-euglycaemic (approximately 5 mmol/l) clamp test. Intramyocellular lipid concentrations were determined by using localized 1H NMR spectroscopy of soleus muscle. Simple linear regression analysis showed an inverse correlation (r = -0.579, p = 0.0037) [corrected] between intramyocellular lipid content and M-value (100-120 min of clamp) as well as between fasting plasma non-esterified fatty acid concentration and M-value (r = -0.54, p = 0.0267). Intramyocellular lipid content was not related to BMI, age and fasting plasma concentrations of triglycerides, non-esterified fatty acids, glucose or insulin. These results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans.

Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.

To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%-60% lower following the lipid infusion compared with the glycerol infusion and were associated with a approximately 90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity.

Efficacy and duration of action of procaterol, a new bronchodilator.

Procaterol, a new beta-adrenergic agonist, was tested in two different doses in patients with reversible airway obstruction. Single oral doses of 0.05 or 0.1 mg produce an increase in measured expiratory flow rates, and the peak and duration of action are both dose related. Side effects reported during this one-day study were similar to those described with other compounds of this class; they were considered to be mild by the patients and the investigator. From these results, further investigation of this agent in bronchoconstrictive disease appears warranted.