Breathing Movements Research Articles

The Effect of Three Different Positioning Approaches for Prone Rectum Radiotherapy on Positioning Accuracy and Treatment Margins

The positioning accuracy of rectal radiotherapy patients was greatly affected by the immobilization gadget, breathing motion, bladder volume etc. Prone is one of the common treatment positions for rectum radiotherapy patients as it can displace the small bowels to reduce side effects. Our team would like to further enhance positioning accuracy by evaluating different positioning approaches. A total of 16 patients from each group were selected retrospectively. All patients fulfilled the bladder (±20% of CT-sim bladder volume) and bowel (empty bowel before the treatment) protocol before entering the treatment unit. Group A patients were positioned using commercial prone pelvic board (Orfit, Belgium) combined with thermoplastic membrane and skin markings; Group B patients were fixed with innovative prone pelvic board and vac-bag which positioned using skin markings. First three fractions and once weekly CBCT images were retrieved for data analysis. Group C patients were fixed the same as Group B and positioned using skin markings during the first fraction. New reference surface for the SGRT system (Vision RT Ltd, UK) was captured after CBCT shifts applied. The subsequent treatment, patient was aligned to ±0.1 cm and ±1.5° according to the new reference surface. CBCT shifts that were taken at fraction 2, 3, 4 and once weekly were recorded in 6 degrees of freedom. A total of 112 sets of data were retrieved from each groups respectively. The results were compared using nonparametric tests based on the normal distribution of the data. PTV margins (M) were calculated using the formula M = 2.5Σ+0.7σ. Positioning errors were shown in Table 1. The median positioning errors was statistically significant in lateral, vertical, roll and yaw for Group A and B. Whereas, Group C positioning errors was superior to Group B in all axes (p<0.05) except roll and yaw directions. The margins of Group A, B and C were 0.68cm, 1.17cm and 0.62cm; 0.56cm, 0.99cm and 0.75cm; 0.39cm, 0.36cm and 0.34cm in lateral, longitudinal and vertical directions. The results shown that Group B margins was smaller than Group A in lateral and longitudinal directions. Group C required the least margins. Positioning prone rectum patients using innovative pelvic board with the aid of surface guidance resulted in higher accuracy and smaller margins especially in longitudinal direction. Accurate positioning and good reproducibility could potentially reduce the margins from 6mm to 4mm for our prone rectum radiotherapy patients.

Real Time Volumetric MRI for MR-Guided 3D Motion Tracking via Sparse Prior-Augmented Neural Representation Learning

To reconstruct volumetric MRI from orthogonal cine acquisition aided by sparse priors of 2 static 3D MRI through implicit neural representation (NeRP) learning, with the goal of eliminating large-scale training datasets for data-driven sparse MRI reconstruction and supporting clinical workflow of real time 3D motion tracking during MR-guided radiotherapy. A multi-layer perceptron network was trained to learn the NeRP of a patient-specific MRI dataset, where the network takes 4D data coordinates of voxel locations and motion states as inputs and outputs corresponding voxel intensities. By first learning the NeRP of 2 static 3D MRI with different breathing motion states, prior knowledge of patient breathing motion was embedded into network weights through optimization. The prior knowledge was then augmented from 2 to 31 motion states by querying the optimized network at interpolated/extrapolated motion state coordinates. Starting from the prior-augmented network as an initialization point, the network was further trained using sparse samples of 2 orthogonal cine slices. The final volumetric reconstruction was obtained by querying the trained network at desired 3D spatial locations. We evaluated the proposed method using 5-minute volumetric MRI time series with 340 ms temporal resolution collected from 7 liver carcinoma patients. The time series was acquired using golden-angle radial MRI sequence and reconstructed through retrospective sorting. Two MRI with inhale and exhale states respectively were selected from the first 30 sec of the time series for prior embedding and augmentation. The remaining 4.5-min time series was used for volumetric reconstruction evaluation, where we retrospectively subsampled each MRI to 2 orthogonal slices and compared network-reconstructed images to ground truth images in terms of image quality and the capability of supporting 3D target motion tracking. Across the 7 patients evaluated, the peak signal to noise ratio between model reconstruction and ground truth was 54.66 ± 6.16 dB and the structural similarity index measure was 0.99 ± 0.01. Gross tumor volume (GTV) contours estimated by deforming a reference state MRI to model-reconstructed and ground truth MRI showed good consistency. The 95-percentile Hausdorff distance between GTV contours was 1.89 ± 1.13 mm, which is less than the voxel dimension. The mean GTV centroid position difference between ground truth and model estimation was less than 1 mm in all 3 orthogonal directions. Volumetric MRI from orthogonal cine acquisition with sparse priors is feasible by modeling prior knowledge through implicit neural representation learning. The model-reconstructed images showed sufficient accuracy in supporting 3D motion tracking of abdominal targets. By eliminating the need for large scale training datasets, the method promises to enable clinical implementation of 3D motion tracking for precision radiation therapy.

Impact of Breast Volume on Achieving a Conservative Heart and Target Coverage Metric for Patients Receiving Whole Breast Radiotherapy in a Statewide Consortium

Radiation to large breast volumes (BV) has been associated with increased dose inhomogeneities, breast fibrosis, and induration. Radiation exposure to the heart during breast radiotherapy has been associated with late cardiovascular morbidity and mortality. This study, therefore, investigates the impact of BV on achieving optimal lumpectomy cavity target coverage (V95% [%] >95) while maintaining mean heart dose constraints (MHD, mean [Gy] <1) across a range of BV from patients enrolled in a statewide consortium. A retrospective analysis was conducted for 2,506 patients receiving left-sided whole breast moderately-hypofractionated (2.5-2.8 Gy/fx) radiotherapy without nodal fields between 2018-2022. The BV was calculated for each patient from contours in the treatment planning system, and the volume distribution partitioned into quartiles. Dosimetric parameters were calculated from dose-volume histograms. The percentage of patients in which the metrics were achieved was calculated for each BV quartile for different treatment positions: all positions, supine, supine with breathing motion management, and prone. The BV ranges within the quartiles (∼620 patients/quartile) were ≤720.0 cc, 720.1 to ≤1065.0 cc, 1065.1 to ≤1500.0 cc, and >1500.0 cc for quartiles Q1-Q4, respectively. Of the 2,506 patients, 76% were treated supine (of which 41.6% were treated using breathing motion management techniques), 23.5% were treated prone, and 0.5% were treated decubitus. Discrete percentages of patients able to meet the metrics are provided in the table. An increase in BV from Q1 to Q4 correlated with lower percentages of patients meeting the MHD metric, however no correlation was observed between BV and target coverage. Treating supine with breathing motion management resulted in a higher percentage of patients meeting the MHD metric (odds ratio (OR) = 1.96 relative to supine without motion management, p<0.0001), while the prone setup proved to be the superior technique across all quartiles (OR = 3.95 relative to supine, p<0.0001). Increasing BVs resulted in lower percentages of patients receiving MHD≤1 Gy. Thus, cardiac sparing may be more difficult to achieve in patients with larger BV. Utilization of alternate treatment positions, such as supine with breathing motion management and prone, greatly improved the percentage of patients able to meet the MHD metric without sacrificing target coverage in all quartiles. Prone positioning was the technique least susceptible to BV effects in meeting the MHD≤1 Gy goal.

Enhancing Clinical Accuracy in DIBH Pattern Detection with a Combined Ultrasonic and IR Sensor System

This study aimed to develop a DIBH monitoring system using IR (Infrared- VL6180X Time of Flight) distance sensors and a microcontroller, and to demonstrate its functionality and performance in various irregular free and DIBH breathings from the left breast and lung patients. A total of ten patients who performed DIBH breathing for treatment planning and optimized treatment delivery were randomly selected for the study. The breathing motion of the system was tested using an RPM (Real-Time Positioning Management) phantom. The IR sensors were interfaced with an Arduino microcontroller, and a body phantom was used to mimic the DIBH pattern on a CT scan. The detector holder was mounted perpendicularly between the xiphoid and umbilicus, with the ability to compensate for various patient body habitus and adapt to clinical setups. The plastic devices were 3D printed, and the sensors were mounted approximately 100mm apart to receive directed echo signals and prevent unwanted signals from scattering. The IR sensor DIBH system was able to detect and record the patient's breathing pattern in real-time. The IR sensor showed better visualization of breathing rhythm with fewer fluctuations and reduced noise than the previous ultrasonic sensor system. The breathing amplitude and duration for the patients were compared to our treatment planning of Varian Eclipse and verified in TrueBeam's Breath-Hold Gating mode. The amplitude and duration from the primary study were measured to ±5mm, including 3mm sensor noise level and ±1.5 second. The IR sensor DIBH system demonstrated better performance compared to the ultrasonic sensor, with a better visualization of breathing rhythm and reduced fluctuations and noise. It provided a clinically acceptable DIBH pattern for monitoring chest and abdominal motion in patients with irregular breathing. The findings of this study have the potential to enhance clinical accuracy in radiation therapy treatment planning and delivery for patients undergoing DIBH.

Quantification of Hepatocellular Carcinoma Vascular Dynamics With Contrast-Enhanced Ultrasound for LI-RADS Implementation.

The aim of this study is to describe a comprehensive contrast-enhanced ultrasound (CEUS) imaging protocol and analysis method to implement CEUS LI-RADS (Liver Imaging Reporting and Data System) in a quantifiable manner. The methods that are validated with a prospective single-center study aim to simplify CEUS LI-RADS evaluation, remove observer bias, and potentially improve the sensitivity of CEUS LI-RADS. This prospective single-center study enrolled patients with hepatocellular carcinoma (April 2021-June 2022; N = 31; mean age ± SD, 67 ± 6 years; 24 men/7 women). For each patient, at least 2 CEUS loops spanning over 5 minutes were collected for different lesion scan planes using an articulated arm to hold the transducer. Automatic respiratory gating and motion compensation algorithms removed errors due to breathing motion. The long axis of the lesion was measured in the contrast and fundamental images to capture nodule size. Parametric processing of time-intensity curve analysis on linearized data provided quantifiable information of the wash-in and washout dynamics via rise time ( RT ) and degree of washout ( DW ) parameters extracted from the time-intensity curve, respectively. A Welch t test was performed between lesion and parenchyma RT for each lesion to confirm statistically significant differences. P values for bootstrapped 95% confidence intervals of the relative degree of washout ( rDW ), ratio of DW between the lesion and surrounding parenchyma, were computed to quantify lesion washout. Coefficient of variation (COV) of RT , DW , and rDW was calculated for each patient between injections for both the lesion and surrounding parenchyma to gauge reproducibility of these metrics. Spearman rank correlation tests were performed among size, RT , DW , and rDW values to evaluate statistical dependence between the variables. The mean ± SD lesion diameter was 23 ± 8 mm. The RT for all lesions, capturing arterial phase hyperenhancement, was shorter than that of surrounding liver parenchyma ( P < 0.05). All lesions also demonstrated significant ( P < 0.05) but variable levels of washout at both 2-minute and 5-minute time points, quantified in rDW . The COV of RT for the lesion and surrounding parenchyma were both 11%, and the COV of DW and rDW at 2 and 5 minutes ranged from 22% to 31%. Statistically significant relationships between lesion and parenchyma RT and between lesion RT and lesion DW at the 2- and 5-minute time points were found ( P < 0.05). The imaging protocol and analysis method presented provide robust, quantitative metrics that describe the dynamic vascular patterns of LI-RADS 5 lesions classified as hepatocellular carcinomas. The RT of the bolus transit quantifies the arterial phase hyperenhancement, and the DW and rDW parameters quantify the washout from linearized CEUS intensity data. This unique methodology is able to implement the CEUS-LIRADS scheme in a quantifiable manner for the first time and remove its existing issues of currently being qualitative and suffering from subjective evaluations.

Stage separation of recoverable liquid launch vehicle by using moving pulsating ball analogue for propellant sloshing

In the process of stage separation of recoverable liquid launch vehicles, because of the large amount of residual fuel in the storage tanks, the influence of liquid sloshing on separation safety must be considered. Considering calculation simplicity and operation practicability, the Moving Pulsating Ball Model (MPBM) of large amplitude liquid sloshing is introduced into the calculation of launch vehicle stage separation. Combining the dynamic equation of the model with the energy relationship during “breathing movement”, the formula calculating the force of liquid on the rigid body is derived. Compared with the calculations of commercial CFD calculation software, the accuracy of MPBM model is verified. Then, all the external forces and moments are applied to the rigid body of the stages, so that the translational and rotational dynamic equations of the stages are obtained respectively. According to the relative position of the two stages, the geometric shape of the interstage section and the engine of the second stage, the minimum clearance in the separation process can be decided to guarantee that the separation process is safe.

Wavelet Analysis of Respiratory Muscle sEMG Signals during the Physiological Breakpoint of Static Dry End-Expiratory Breath-Holding in Naive Apneists: A Pilot Study.

The wavelet spectral characteristics of three respiratory muscle signals (scalenus (SC), parasternal intercostal (IC), and rectus abdominis (RA)) and one locomotor muscle (brachioradialis (BR)) were analyzed in the time-frequency (T-F) domain during voluntary breath-holding (BH), with a focus on the physiological breakpoint that is commonly considered the first involuntary breathing movement (IBM) that signals the end of the easy-going phase of BH. The study was performed for an end-expiratory BH physiological breaking point maneuver on twelve healthy, physically active, naive breath-holders/apneists (six professional athletes; six recreational athletes, and two individuals in the post-COVID-19 period) using surface electromyography (sEMG). We observed individual effects that were dependent on muscle oxygenation and each person's fitness, which were consistent with the mechanism of motor unit (MU) recruitment and the transition of slow-twitch oxidative (type 1) to fast-twitch glycolytic (type 2) muscle fibers. Professional athletes had longer BH durations (BHDs) and strong hypercapnic responses regarding the expiratory RA muscle, which is activated abruptly at higher BHDs in a person-specific range below 250 Hz and is dependent on the BHD. This is in contrast with recreational athletes, who had strong hypoxic responses regarding inspiratory IC muscle, which is activated faster and gradually in the frequency range of 250-450 Hz (independent of the person and BHD). This pilot study preliminarily indicates that it is possible to noninvasively assess the physiological characteristics of skeletal muscles, especially oxygenation, and improve physical fitness tests by determining the T-F features of elevated myoelectric IC and RA activity during BH.

Cone-beam CT in lung biopsy: a clinical practice review on lessons learned and future perspectives.

Pulmonary nodules with intermediate to high risk of malignancy should preferably be diagnosed with image guide minimally invasive diagnostics before treatment. Several technological innovations have been developed to endobronchially navigate to these lesions and obtain tissue for diagnosis. This review addresses these technological advancements in navigation bronchoscopy in three basic steps: navigation, position confirmation and acquisition, with a specific focus on cone-beam computed tomography (CBCT). For navigation purposes ultrathin bronchoscopy combined with virtual bronchoscopy navigation, electromagnetic navigation and robotic assisted bronchoscopy all achieve good results as a navigation guidance tool, but cannot confirm location or guide biopsy positioning. Diagnostic yield has seen improvement by combining these techniques with a secondary imaging tool like radial endobronchial ultrasound (rEBUS) and fluoroscopy. For confirmation of lesion access, rEBUS provides local detailed ultrasound-imaging and can be used to confirm lesion access in combination with fluoroscopy, measure nodule-contact area length and determine catheter position for sampling. CBCT is the only technology that can provide precise 3D positioning confirmation. When focusing on tissue acquisition, there is often more than 10% difference between reaching the target and getting a diagnosis. This discrepancy is multifactorial and caused by breathing movements, small samples sizes, instrument tip displacements by tool rigidity and tumour inhomogeneity. Yield can be improved by targeting fluorodeoxyglucose (FDG)-avid regions, immediate feedback of rapid onsite evaluation, choosing sampling tools with different passive stiffnesses, by increasing the number biopsies taken and (future) catheter modifications like (robotic assisted-) active steering. CBCT with augmented fluoroscopy (CBCT-AF) based navigation bronchoscopy combines navigation guidance with 3D-image confirmation of instrument-in-lesion positioning in one device. CBCT-AF allows for overlaying the lesion and navigation pathway and the possibility to outline trans-parenchymal pathways. It can help guide and verify sampling in 3D in near real-time. Disadvantages are the learning curve, the inherent use of radiation and limited availability/access to hybrid theatres. A mobile C-arm can provide 3D imaging, but lower image quality due to lower power and lower contrast-to-noise ratio is a limiting factor. In conclusion, a multi-modality approach in experienced hands seems the best option for achieving a diagnostic accuracy >85%. Either adequate case selection or detailed 3D imaging are essential to obtain high accuracy. For current and future transbronchial treatments, high-resolution (CBCT) 3D-imaging is essential.

High-fidelity Database-free Deep Learning Reconstruction for Real-time Cine Cardiac MRI.

Real-time cine cardiac MRI provides an ECG-free free-breathing alternative to clinical gold-standard ECG-gated breath-hold segmented cine MRI for evaluation of heart function. Real-time cine MRI data acquisition during free breathing snapshot imaging enables imaging of patient cohorts that cannot be imaged with segmented or breath-hold acquisitions, but requires rapid imaging to achieve sufficient spatial-temporal resolutions. However, at high acceleration rates, conventional reconstruction techniques suffer from residual aliasing and temporal blurring, including advanced methods such as compressed sensing with radial trajectories. Recently, deep learning (DL) reconstruction has emerged as a powerful tool in MRI. However, its utility for free-breathing real-time cine MRI has been limited, as database-learning of spatio-temporal correlations with varying breathing and cardiac motion patterns across subjects has been challenging. Zero-shot self-supervised physics-guided deep learning (PG-DL) reconstruction has been proposed to overcome such challenges of database training by enabling subject-specific training. In this work, we adapt zero-shot PG-DL for real-time cine MRI with a spatio-temporal regularization. We compare our method to TGRAPPA, locally low-rank (LLR) regularized reconstruction and database-trained PG-DL reconstruction, both for retrospectively and prospectively accelerated datasets. Results on highly accelerated real-time Cartesian cine MRI show that the proposed method outperforms other reconstruction methods, both visibly in terms of noise and aliasing, and quantitatively.

Optimization of non-endorectal prostate MR image quality using PI-QUAL: A multidisciplinary team approach

PurposeTo evaluate the utility of the PI-QUAL score in assessing protocol changes aimed to improve image quality from a non-endorectal coil prostate MR imaging protocol during a 9-month quality improvement (QI) project and to quantify the inter-reader agreement of PI-QUAL scores between radiologists, technologists, and physicists. MethodsThis retrospective study audited 1,012 multiparametric prostate MRI examinations as part of a national QI project according to the PI-QUAL standard. PI-QUAL scores were used to inform MR protocol changes. Following the project, 4 radiologists, 2 technologists, and 1 medical physicist collectively audited an additional set of 150 examinations to identify statistical improvements in image quality using the two-tailed Wilcoxon rank sum test. The improvements due to individual protocol changes were assessed among subsets of the 1,012 examinations which compared examinations occurring before and after the isolated protocol change. Inter-reader variability was assessed using the percent majority agreement and the average standard deviation of PI-QUAL scores between evaluators. ResultsDuring this QI project, PI-QUAL scores improved from 3.67 ± 0.75 to 4.16 ± 0.59 (p < 0.01) after implementing a series of protocol changes. Among a subset of 451 cases, we found that adopting R/L rather than A/P phase encoding reduced distortion in diffusion-weighted imaging (DW) from 21.6% (41/190 A/P phase encoded cases) to 11.5% (30/261 R/L phase encoded cases) (p < 0.01). Similarly, in the same 451 cases, adopting R/L phase encoding in T2WI reduced breathing motion artifacts from 34.6% (94/272 A/P phase encoding cases) to 12.8% (23/179 R/L phase encoding cases) (p < 0.01). DWI wraparound artifact was mitigated by employing a full-pelvis shim and enabling the abdomen shim option. The occurrence of low signal-to-noise ratio was reduced from 19.4% (19/98 cases without a weight-based threshold) to 6.3% (10/160) by instituting a weight-based threshold for using an endorectal coil (p < 0.01). The percent majority agreement was similar between radiologists, technologists and physicists, and all evaluators combined (72%, 77%, and 67%, respectively). ConclusionsPI-QUAL can evaluate image quality changes resulting from protocol optimizations at both the exam- and series-levels. With training, radiologists, technologists, and physicists can perform PI-QUAL scoring with similar performance. Broadening the scope of the quality improvement team can result in meaningful and lasting change.

Peptide-Functionalized Electrospun Meshes for the Physiological Cultivation of Pulmonary Alveolar Capillary Barrier Models in a 3D-Printed Micro-Bioreactor.

In vitro environments that realize biomimetic scaffolds, cellular composition, physiological shear, and strain are integral to developing tissue models of organ-specific functions. In this study, an in vitro pulmonary alveolar capillary barrier model is developed that closely mimics physiological functions by combining a synthetic biofunctionalized nanofibrous membrane system with a novel three-dimensional (3D)-printed bioreactor. The fiber meshes are fabricated from a mixture of polycaprolactone (PCL), 6-armed star-shaped isocyanate-terminated poly(ethylene glycol) (sPEG-NCO), and Arg-Gly-Asp (RGD) peptides by a one-step electrospinning process that offers full control over the fiber surface chemistry. The tunable meshes are mounted within the bioreactor where they support the co-cultivation of pulmonary epithelial (NCI-H441) and endothelial (HPMEC) cell monolayers at air-liquid interface under controlled stimulation by fluid shear stress and cyclic distention. This stimulation, which closely mimics blood circulation and breathing motion, is observed to impact alveolar endothelial cytoskeleton arrangement and improve epithelial tight junction formation as well as surfactant protein B production compared to static models. The results highlight the potential of PCL-sPEG-NCO:RGD nanofibrous scaffolds in combination with a 3D-printed bioreactor system as a platform to reconstruct and enhance in vitro models to bear a close resemblance to in vivo tissues.

Parameter based 4D dose calculations for proton therapy.

Background and purpose Retrospective log file-based analysis provides the actual dose delivered based on the patient's breathing and the daily beam-delivery dynamics. To predict the motion sensitivity of the treatment plan on a patient-specific basis before treatment start a prospective tool is required. Such a parameter-based tool has been investigated with the aim to be used in clinical routine. Materials and Methods 4D dose calculations (4DDC) were performed for seven cancer patients with small breathing motion treated with scanned pulsed proton beams. Validation of the parameter-based 4DDC (p-4DDC) method was performed with an anthropomorphic phantom and patient data employing measurements and a log file-based 4DDC tool. The dose volume histogram parameters () were investigated for the target and the organs at risk, compared to static and the file-based approach. Results The difference between the measured and the p-4DDC dose was within the deviation of the measurements. The maximum deviation was 0.4Gy. For the planning target volume varied up to 15% compared to the static scenario, while the results from the log file and p-4DDC agreed within 2%. For the liver patients, deviated up to 35% compared to static and 10% comparing the two 4DDC tools, while for the pancreas patients the varied up to 45% and 11%, respectively. Conclusion The results showed that p-4DDC could be used prospectively. The next step will be the clinical implementation of the p-4DDC tool, which can support a decision to either adapt the treatment plan or apply motion mitigation strategies.

A Correction Method for Muscle Stiffness Sensors to Measure Transversus Abdominis Activity

The transversus abdominis muscle is important for various human functions, including the prevention of back pain and the use of muscle activity values as an indicator for the treatment of urinary incontinence. Measuring muscle activity is an effective means of evaluating whether correct training has been performed. The transversus abdominis muscle stiffness sensor developed in a previous study used a method in which a belt with a sensor attached was wrapped around the lower back, which made measurement simple but also caused problems owing to the influence of phenomena other than muscle activity on the measurement data. Therefore, we propose a novel correction method to calculate the muscle activity of this sensor accurately, which can be used for simple measurements. We propose a formula to compensate for effects other than muscle activity based on a model equation that includes contact conditions and belt tension, which affect the muscle stiffness sensor value. We evaluated the validity of the correction equation from simulations and the change in similarity owing to the correction by simultaneously measuring the muscle action potentials and muscle stiffness sensor values during breathing movements with muscle activity. The proposed correction method improved the muscle stiffness data during respiration and contraction. It is possible to improve the measurement accuracy by improving the calibration method and hardware.

Unobtrusive cot side sleep stage classification in preterm infants using ultra-wideband radar

BackgroundSleep is an important driver of development in infants born preterm. However, continuous unobtrusive sleep monitoring of infants in the neonatal intensive care unit (NICU) is challenging.ObjectiveTo assess the feasibility of ultra-wideband (UWB) radar for sleep stage classification in preterm infants admitted to the NICU.MethodsActive and quiet sleep were visually assessed using video recordings in 10 preterm infants (recorded between 29 and 34 weeks of postmenstrual age) admitted to the NICU. UWB radar recorded all infant's motions during the video recordings. From the baseband data measured with the UWB radar, a total of 48 features were calculated. All features were related to body and breathing movements. Six machine learning classifiers were compared regarding their ability to reliably classify active and quiet sleep using these raw signals.ResultsThe adaptive boosting (AdaBoost) classifier achieved the highest balanced accuracy (81%) over a 10-fold cross-validation, with an area under the curve of receiver operating characteristics (AUC-ROC) of 0.82.ConclusionsThe UWB radar data, using the AdaBoost classifier, is a promising method for non-obtrusive sleep stage assessment in very preterm infants admitted to the NICU.

High-speed low-noise optical respiratory monitoring for spot scanning proton therapy

PurposeTo investigate a novel optical markerless respiratory sensor for surface guided spot scanning proton therapy and to measure its main technical characteristics. MethodsThe main characteristics of the respiratory sensor including sensitivity, linearity, noise, signal-to-noise, and time delay were measured using a dynamic phantom and electrical measuring equipment on a laboratory stand. The respiratory signals of free breathing and deep-inspiration breath-hold patterns were acquired for various distances with a volunteer. A comparative analysis of this sensor with existing commercially available and experimental respiratory monitoring systems was carried out based on several criteria including principle of operation, patient contact, application to proton therapy, distance range, accuracy (noise, signal-to-noise ratio), and time delay (sampling rate). ResultsThe sensor provides optical respiratory monitoring of the chest surface over a distance range of 0.4–1.2 m with the RMS noise of 0.03–0.60 mm, SNR of 40–15 dB (for motion with peak-to-peak of 10 mm), and time delay of 1.2 ± 0.2 ms. ConclusionsThe investigated optical respiratory sensor was found to be appropriate to use in surface guided spot scanning proton therapy. This sensor combined with a fast respiratory signal processing algorithm may provide accurate beam control and a fast response in patients’ irregular breathing movements. A careful study of correlation between the respiratory signal and 4DCT data of tumor position will be required before clinical implementation.

NMR approaches to study proteins integrating globular and disordered domains: the case of c-Src

Abstract Nuclear Magnetic Resonance is one of the most versatile structural biology tools. Its unique capacities remain unchallenged by the advances in other techniques, experimental, like cryo-electron microscopy, or computational, such as AlphaFold. In this perspective article we present the role played by various NMR techniques in the study of c-Src, a non-receptor protein tyrosine kinase that contains globular and intrinsically disordered domains. We show (i) how NMR helped chemical biology to discover the regulatory role of the Unique domain, (ii) its role in the characterization of the fuzzy intramolecular complex connecting the disordered region with the globular core through the SH3 domain, (iii) the identification of salt bridges connecting the main post-translational sites of the Unique domain with neighbor basic residues, and, (iv) the characterization of breathing motions and the independent dynamics of the two lobes of the kinase domain.

Dosimetric Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy.

Background Breathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. Method The study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liver-directed SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20and V30. Statistical analyses were performed to compare results. Results The findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. Conclusion This dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.

Reduced dynamic complexity allows structure elucidation of an excited state of KRASG13D

Localized dynamics of RAS, including regions distal to the nucleotide-binding site, is of high interest for elucidating the mechanisms by which RAS proteins interact with effectors and regulators and for designing inhibitors. Among several oncogenic mutants, methyl relaxation dispersion experiments reveal highly synchronized conformational dynamics in the active (GMPPNP-bound) KRASG13D, which suggests an exchange between two conformational states in solution. Methyl and 31P NMR spectra of active KRASG13D in solution confirm a two-state ensemble interconverting on the millisecond timescale, with a major Pγ atom peak corresponding to the dominant State 1 conformation and a secondary peak indicating an intermediate state different from the known State 2 conformation recognized by RAS effectors. High-resolution crystal structures of active KRASG13D and KRASG13D-RAF1 RBD complex provide snapshots of the State 1 and 2 conformations, respectively. We use residual dipolar couplings to solve and cross-validate the structure of the intermediate state of active KRASG13D, showing a conformation distinct from those of States 1 and 2 outside the known flexible switch regions. The dynamic coupling between the conformational exchange in the effector lobe and the breathing motion in the allosteric lobe is further validated by a secondary mutation in the allosteric lobe, which affects the conformational population equilibrium.

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

A motion model-guided 4D dose reconstruction for pencil beam scanned proton therapy

Objective. 4D dose reconstruction in proton therapy with pencil beam scanning (PBS) typically relies on a single pre-treatment 4DCT (p4DCT). However, breathing motion during the fractionated treatment can vary considerably in both amplitude and frequency. We present a novel 4D dose reconstruction method combining delivery log files with patient-specific motion models, to account for the dosimetric effect of intra- and inter-fractional breathing variability. Approach. Correlation between an external breathing surrogate and anatomical deformations of the p4DCT is established using principal component analysis. Using motion trajectories of a surface marker acquired during the dose delivery by an optical tracking system, deformable motion fields are retrospectively reconstructed and used to generate time-resolved synthetic 4DCTs (‘5DCTs’) by warping a reference CT. For three abdominal/thoracic patients, treated with respiratory gating and rescanning, example fraction doses were reconstructed using the resulting 5DCTs and delivery log files. The motion model was validated beforehand using leave-one-out cross-validation (LOOCV) with subsequent 4D dose evaluations. Moreover, besides fractional motion, fractional anatomical changes were incorporated as proof of concept. Main results. For motion model validation, the comparison of 4D dose distributions for the original 4DCT and predicted LOOCV resulted in 3%/3 mm gamma pass rates above 96.2%. Prospective gating simulations on the p4DCT can overestimate the target dose coverage V95% by up to 2.1% compared to 4D dose reconstruction based on observed surrogate trajectories. Nevertheless, for the studied clinical cases treated with respiratory-gating and rescanning, an acceptable target coverage was maintained with V95% remaining above 98.8% for all studied fractions. For these gated treatments, larger dosimetric differences occurred due to CT changes than due to breathing variations. Significance. To gain a better estimate of the delivered dose, a retrospective 4D dose reconstruction workflow based on motion data acquired during PBS proton treatments was implemented and validated, thus considering both intra- and inter-fractional motion and anatomy changes.