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The article presents a study which investigates the efficacy of marking the axilla with radioactive iodine seeds (MARI) as a new procedure for treating breast cancer. The results show that this procedure, which involves neoadjuvant chemotherapy, is feasible for treatment of breast cancer. It was concluded that this procedure has the potential when making axilla-conserving surgery in treating breast cancer.

Background: The aim of this systematic qualitative review was to give an overview of reference ranges defined as normal values or centile charts of regional tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) in term and preterm neonates., Methods: A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed. Additional articles were identified by manual search of cited references. Only human studies in neonates were included., Results: Nineteen studies were identified. Eight described regional tissue oxygen saturation during fetal-to-neonatal transition, six during the first 3 days after birth, four during the first 7 days after birth, and one during the first 8 weeks after birth. Nine described regional tissue oxygen saturation in term, nine in preterm neonates, and one in both. Eight studies published centile charts for cerebral regional tissue oxygen saturation, and only five included large cohorts of infants. Eleven studies described normal values for cerebral, muscle, renal, and abdominal regional tissue oxygen saturation, the majority with small sample sizes. Four studies of good methodological quality were identified describing centile charts of cerebral regional tissue oxygen saturation., Conclusions: In clinical settings, quality centile charts are available and should be the preferred method when using NIRS monitoring., Impact: Near-infrared spectroscopy (NIRS) enables a bed-side non-invasive continuous monitoring of tissue oxygenation. When using NIRS monitoring in a clinical setting, centile charts with good quality are available and should be preferred to normal values. High-quality reference ranges of regional tissue oxygenation in term and preterm born neonates are an important step toward routine clinical application of NIRS., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Cerebral oxygenation monitoring utilising near-infrared spectroscopy (NIRS) is increasingly used to guide interventions in clinical care. The objective of this systematic review with meta-analysis and Trial Sequential Analysis is to evaluate the effects of clinical care with access to cerebral NIRS monitoring in children and adults versus care without., Methods: This review conforms to PRISMA guidelines and was registered in PROSPERO (CRD42020202986). Methods are outlined in our protocol (doi: 10.1186/s13643-021-01660-2)., Results: Twenty-five randomised clinical trials were included (2606 participants). All trials were at a high risk of bias. Two trials assessed the effects of NIRS during neonatal intensive care, 13 during cardiac surgery, 9 during non-cardiac surgery and 1 during neurocritical care. Meta-analyses showed no significant difference for all-cause mortality (RR 0.75, 95% CI 0.51-1.10; 1489 participants; I 2  = 0; 11 trials; very low certainty of evidence); moderate or severe, persistent cognitive or neurological deficit (RR 0.74, 95% CI 0.42-1.32; 1135 participants; I 2  = 39.6; 9 trials; very low certainty of evidence); and serious adverse events (RR 0.82; 95% CI 0.67-1.01; 2132 participants; I 2  = 68.4; 17 trials; very low certainty of evidence)., Conclusion: The evidence on the effects of clinical care with access to cerebral NIRS monitoring is very uncertain., Impact: The evidence of the effects of cerebral NIRS versus no NIRS monitoring are very uncertain for mortality, neuroprotection, and serious adverse events. Additional trials to obtain sufficient information size, focusing on lowering bias risk, are required. The first attempt to systematically review randomised clinical trials with meta-analysis to evaluate the effects of cerebral NIRS monitoring by pooling data across various clinical settings. Despite pooling data across clinical settings, study interpretation was not substantially impacted by heterogeneity. We have insufficient evidence to support or reject the clinical use of cerebral NIRS monitoring., (© 2022. The Author(s).)

Study Objectives: The aim of this study was to investigate the relationship between sleep stages and neural microstructure - measured using diffusion tensor imaging - of the posterior limb of the internal capsule and corticospinal tract in preterm infants., Methods: A retrospective cohort of 50 preterm infants born between 24 + 4 and 29 + 3 weeks gestational age was included in the study. Sleep stages were continuously measured for 5-7 consecutive days between 29 + 0 and 31 + 6 weeks postmenstrual age using an in-house-developed, and recently published, automated sleep staging algorithm based on routinely measured heart rate and respiratory rate. Additionally, a diffusion tensor imaging scan was conducted at term equivalent age as part of standard care. Region of interest analysis of the posterior limb of the internal capsule was performed, and tractography was used to analyze the corticospinal tract. The association between sleep and white matter microstructure of the posterior limb of the internal capsule and corticospinal tract was examined using a multiple linear regression model, adjusted for potential confounders., Results: The results of the analyses revealed an interaction effect between sleep stage and days of invasive ventilation on the fractional anisotropy of the left and right posterior limb of the internal capsule (β = 0.04, FDR-adjusted p = 0.001 and β = 0.04, FDR-adjusted p = 0.02, respectively). Furthermore, an interaction effect between sleep stage and days of invasive ventilation was observed for the radial diffusivity of the mean of the left and right PLIC (β = -4.1e-05, FDR-adjusted p = 0.04)., Conclusions: Previous research has shown that, in very preterm infants, invasive ventilation has a negative effect on white matter tract maturation throughout the brain. A positive association between active sleep and white matter microstructure of the posterior limb of the internal capsule, may indicate a protective role of sleep in this vulnerable population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pediatric sleep-related breathing disorders, or sleep-disordered breathing (SDB), cover a range of conditions, including obstructive sleep apnea, central sleep apnea, sleep-related hypoventilation disorders, and sleep-related hypoxemia disorder. Pediatric SDB is often underdiagnosed, potentially due to difficulties associated with performing the gold standard polysomnography in children. This scoping review aims to: (1) provide an overview of the studies reporting on safe, noncontact monitoring of respiration in young children, (2) describe the accuracy of these techniques, and (3) highlight their respective advantages and limitations. PubMed and EMBASE were searched for studies researching techniques in children <12 years old. Both quantitative data and the quality of the studies were analyzed. The evaluation of study quality was conducted using the QUADAS-2 tool. A total of 19 studies were included. Techniques could be grouped into bed-based methods, microwave radar, video, infrared (IR) cameras, and garment-embedded sensors. Most studies either measured respiratory rate (RR) or detected apneas; n = 2 aimed to do both. At present, bed-based approaches are at the forefront of research in noncontact RR monitoring in children, boasting the most sophisticated algorithms in this field. Yet, despite extensive studies, there remains no consensus on a definitive method that outperforms the rest. The accuracies reported by these studies tend to cluster within a similar range, indicating that no single technique has emerged as markedly superior. Notably, all identified methods demonstrate capability in detecting body movements and RR, with reported safety for use in children across the board. Further research into contactless alternatives should focus on cost-effectiveness, ease-of-use, and widespread availability., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Purpose: Without a clear definition of an optimal treatment plan, no optimization model can be perfect. Therefore, instead of automatically finding a single "optimal" plan, finding multiple, yet different near-optimal plans, can be an insightful approach to support radiation oncologists in finding the plan they are looking for., Methods and Materials: BRIGHT is a flexible AI-based optimization method for brachytherapy treatment planning that has already been shown capable of finding high-quality plans that trade-off target volume coverage and healthy tissue sparing. We leverage the flexibility of BRIGHT to find plans with similar dose-volume criteria, yet different dose distributions. We further describe extensions that facilitate fast plan adaptation should planning aims need to be adjusted, and straightforwardly allow incorporating hospital-specific aims besides standard protocols., Results: Results are obtained for prostate (n = 12) and cervix brachytherapy (n = 36). We demonstrate the possible differences in dose distribution for optimized plans with equal dose-volume criteria. We furthermore demonstrate that adding hospital-specific aims enables adhering to hospital-specific practice while still being able to automatically create cervix plans that more often satisfy the EMBRACE-II protocol than clinical practice. Finally, we illustrate the feasibility of fast plan adaptation., Conclusions: Methods such as BRIGHT enable new ways to construct high-quality treatment plans for brachytherapy while offering new insights by making explicit the options one has. In particular, it becomes possible to present to radiation oncologists a manageable set of alternative plans that, from an optimization perspective are equally good, yet differ in terms of coverage-sparing trade-offs and shape of the dose distribution., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

White matter dysmaturation is commonly seen in preterm infants admitted to the neonatal intensive care unit (NICU). Animal research has shown that active sleep is essential for early brain plasticity. This study aimed to determine the potential of active sleep as an early predictor for subsequent white matter development in preterm infants. Using heart and respiratory rates routinely monitored in the NICU, we developed a machine learning-based automated sleep stage classifier in a cohort of 25 preterm infants (12 females). The automated classifier was subsequently applied to a study cohort of 58 preterm infants (31 females) to extract active sleep percentage over 5-7 consecutive days during 29-32 weeks of postmenstrual age. Each of the 58 infants underwent high-quality T2-weighted magnetic resonance brain imaging at term-equivalent age, which was used to measure the total white matter volume. The association between active sleep percentage and white matter volume was examined using a multiple linear regression model adjusted for potential confounders. Using the automated classifier with a superior sleep classification performance [mean area under the receiver operating characteristic curve (AUROC) = 0.87, 95% CI 0.83-0.92], we found that a higher active sleep percentage during the preterm period was significantly associated with an increased white matter volume at term-equivalent age [ β  = 0.31, 95% CI 0.09-0.53, false discovery rate (FDR)-adjusted p -value = 0.021]. Our results extend the positive association between active sleep and early brain development found in animal research to human preterm infants and emphasize the potential benefit of sleep preservation in the NICU setting., (Copyright © 2024 the authors.)

Introduction: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns., Methods: Retrospective multicenter study included infants with gestational age (GA) 24.0-36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA &lt;28.0 (group 1), 28.0-31.9 (group 2), and 32.0-36.0 weeks (group 3). Early MRI (&lt;36 weeks postmenstrual age or &lt;10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0-44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment &lt;-1 SD at 18-24 months corrected age., Results: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8-58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3-4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0-1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1-21.7) around TEA were associated with adverse neurodevelopmental outcomes., Conclusion: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Magnetic resonance imaging (MRI) including diffusion-weighted imaging within seven days after birth is widely used to obtain prognostic information in neonatal encephalopathy (NE) following perinatal asphyxia. Later MRI could be useful for infants without a neonatal MRI or in the case of clinical concerns during follow-up. Therefore, this review evaluates the association between cranial MRI beyond the neonatal period and neurodevelopmental outcomes following NE., Methods: A systematic literature search was performed using PubMed and Embase on cranial MRI between 2 and 24 months after birth and neurodevelopmental outcomes following NE due to perinatal asphyxia. Two independent researchers performed the study selection and risk of bias analysis. Results were separately described for MRI before and after 18 months., Results: Twelve studies were included (high-quality n = 2, moderate-quality n = 6, low-quality n = 4). All reported on MRI at 2-18 months: seven studies demonstrated a significant association between the pattern and/or severity of injury and overall neurodevelopmental outcomes and three showed a significant association with motor outcome. There were insufficient data on non-motor outcomes and the association between MRI at 18-24 months and neurodevelopmental outcomes., Conclusions: Cranial MRI performed between 2 and 18 months after birth is associated with neurodevelopmental outcomes in NE following perinatal asphyxia. However, more data on the association with non-motor outcomes are needed.

Background: Developmental care is designed to optimize early brain maturation by integrating procedures that support a healing environment. Protecting preterm sleep is important in developmental care. However, it is unclear to what extent healthcare professionals are aware of the importance of sleep and how sleep is currently implemented in the day-to-day care in the neonatal intensive care unit (NICU)., Purpose: Identifying the current state of knowledge among healthcare professionals regarding neonatal sleep and how this is transferred to practice., Methods: A survey was distributed among Dutch healthcare professionals. Three categories of data were sought, including (1) demographics of respondents; (2) questions relating to sleep practices; and (3) objective knowledge questions relating to sleep physiology and importance of sleep. Data were analyzed using Spearman's rho test and Cramer's V test. Furthermore, frequency tables and qualitative analyses were employed., Results: The survey was completed by 427 participants from 34 hospitals in 25 Dutch cities. While healthcare professionals reported sleep to be especially important for neonates admitted in the NICU, low scores were achieved in the area of knowledge of sleep physiology. Most healthcare professionals (91.8%) adapted the timing of elective care procedures to sleep. However, sleep assessments were not based on scientific knowledge. Therefore, the difference between active sleep and wakefulness may often be wrongly assessed. Finally, sleep is rarely discussed between colleagues (27.4% regularly/always) and during rounds (7.5%-14.3% often/always)., Implications: Knowledge about sleep physiology should be increased through education among neonatal healthcare professionals. Furthermore, sleep should be considered more often during rounds and handovers., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the National Association of Neonatal Nurses.)

Unobtrusive monitoring of children's heart rate (HR) and respiratory rate (RR) can be valuable for promoting the early detection of potential health issues, improving communication with healthcare providers and reducing unnecessary hospital visits. A promising solution for wireless vital sign monitoring is radar technology. This paper presents a novel approach for the simultaneous estimation of children's RR and HR utilizing ultra-wideband (UWB) radar using a deep transfer learning algorithm in a cohort of 55 children. The HR and RR are calculated by processing radar signals via spectrogram from time epochs of 10 s (25 sample length of hamming window with 90% overlap) and then transforming the resultant representation into 2-dimensional images. These images were fed into a pre-trained Visual Geometry Group-16 (VGG-16) model (trained on ImageNet dataset), with weights of five added layers fine-tuned using the proposed data. The prediction on the test data achieved a mean absolute error (MAE) of 7.3 beats per minute (BPM < 6.5% of average HR) and 2.63 breaths per minute (BPM < 7% of average RR). We also achieved a significant Pearson's correlation of 77% and 81% between true and extracted for HR and RR, respectively. HR and RR samples are extracted every 10 s.

Objective: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia., Methods: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy., Results: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59., Conclusions: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Critical congenital heart disease (cCHD)-requiring cardiac intervention in the first year of life for survival-occurs globally in 2-3 of every 1000 live births. In the critical perioperative period, intensive multimodal monitoring at a pediatric intensive care unit (PICU) is warranted, as their organs-especially the brain-may be severely injured due to hemodynamic and respiratory events. These 24/7 clinical data streams yield large quantities of high-frequency data, which are challenging in terms of interpretation due to the varying and dynamic physiology innate to cCHD. Through advanced data science algorithms, these dynamic data can be condensed into comprehensible information, reducing the cognitive load on the medical team and providing data-driven monitoring support through automated detection of clinical deterioration, which may facilitate timely intervention., Objective: This study aimed to develop a clinical deterioration detection algorithm for PICU patients with cCHD., Methods: Retrospectively, synchronous per-second data of cerebral regional oxygen saturation (rSO 2 ) and 4 vital parameters (respiratory rate, heart rate, oxygen saturation, and invasive mean blood pressure) in neonates with cCHD admitted to the University Medical Center Utrecht, the Netherlands, between 2002 and 2018 were extracted. Patients were stratified based on mean oxygen saturation during admission to account for physiological differences between acyanotic and cyanotic cCHD. Each subset was used to train our algorithm in classifying data as either stable, unstable, or sensor dysfunction. The algorithm was designed to detect combinations of parameters abnormal to the stratified subpopulation and significant deviations from the patient's unique baseline, which were further analyzed to distinguish clinical improvement from deterioration. Novel data were used for testing, visualized in detail, and internally validated by pediatric intensivists., Results: A retrospective query yielded 4600 hours and 209 hours of per-second data in 78 and 10 neonates for, respectively, training and testing purposes. During testing, stable episodes occurred 153 times, of which 134 (88%) were correctly detected. Unstable episodes were correctly noted in 46 of 57 (81%) observed episodes. Twelve expert-confirmed unstable episodes were missed in testing. Time-percentual accuracy was 93% and 77% for, respectively, stable and unstable episodes. A total of 138 sensorial dysfunctions were detected, of which 130 (94%) were correct., Conclusions: In this proof-of-concept study, a clinical deterioration detection algorithm was developed and retrospectively evaluated to classify clinical stability and instability, achieving reasonable performance considering the heterogeneous population of neonates with cCHD. Combined analysis of baseline (ie, patient-specific) deviations and simultaneous parameter-shifting (ie, population-specific) proofs would be promising with respect to enhancing applicability to heterogeneous critically ill pediatric populations. After prospective validation, the current-and comparable-models may, in the future, be used in the automated detection of clinical deterioration and eventually provide data-driven monitoring support to the medical team, allowing for timely intervention., (©Ruben S Zoodsma, Rian Bosch, Thomas Alderliesten, Casper W Bollen, Teus H Kappen, Erik Koomen, Arno Siebes, Joppe Nijman. Originally published in JMIR Cardio (https://cardio.jmir.org), 16.05.2023.)

Background: Near-infrared spectroscopy (NIRS) relative concentration signals contain 'noise' from physiological processes such as respiration and heart rate. Simultaneous assessment of NIRS and respiratory rate (RR) using a single sensor would facilitate a perfectly time-synced assessment of (cerebral) physiology. Our aim was to extract respiratory rate from cerebral NIRS intensity signals in neonates admitted to a neonatal intensive care unit (NICU). Methods: A novel algorithm, NRR (NIRS RR), is developed for extracting RR from NIRS signals recorded from critically ill neonates. In total, 19 measurements were recorded from ten neonates admitted to the NICU with a gestational age and birth weight of 38 ± 5 weeks and 3092 ± 990 g, respectively. We synchronously recorded NIRS and reference RR signals sampled at 100 Hz and 0.5 Hz, respectively. The performance of the NRR algorithm is assessed in terms of the agreement and linear correlation between the reference and extracted RRs, and it is compared statistically with that of two existing methods. Results: The NRR algorithm showed a mean error of 1.1 breaths per minute (BPM), a root mean square error of 3.8 BPM, and Bland-Altman limits of agreement of 6.7 BPM averaged over all measurements. In addition, a linear correlation of 84.5% ( p < 0.01) was achieved between the reference and extracted RRs. The statistical analyses confirmed the significant ( p < 0.05) outperformance of the NRR algorithm with respect to the existing methods. Conclusions: We showed the possibility of extracting RR from neonatal NIRS in an intensive care environment, which showed high correspondence with the reference RR recorded. Adding the NRR algorithm to a NIRS system provides the opportunity to record synchronously different physiological sources of information about cerebral perfusion and respiration by a single monitoring system. This allows for a concurrent integrated analysis of the impact of breathing (including apnea) on cerebral hemodynamics.

Background: Patients with brain, head, and neck tumors experience a decline in their quality of life due to radiation retinopathy and optic neuropathy. Little is known about the dose-response relationship and patient characteristics. We aimed to systematically review the prevalence of radiation retinopathy and optic neuropathy., Method: The primary outcome was the pooled prevalence of radiation retinopathy and optic neuropathy. The secondary outcome included the effect of the total radiation dose prescribed for the tumor according to the patient's characteristics. Furthermore, we aimed to evaluate the radiation dose parameters for organs at risk of radiation retinopathy and optic neuropathy., Results: The pooled prevalence was 3.8%. No retinopathy was reported for the tumor's prescribed dose of <50 Gy. Optic neuropathy was more prevalent for a prescribed dose of >50 Gy than <50 Gy. We observed a higher prevalence rate for retinopathy (6.0%) than optic neuropathy (2.0%). Insufficient data on the dose for organs at risk were reported., Conclusion: The prevalence of radiation retinopathy was higher compared to optic neuropathy. This review emphasizes the need for future studies considering retinopathy and optic neuropathy as primary objective parameters.

Objective: To investigate the relation between duration of hemodynamically significant patent ductus arteriosus (PDA), cerebral oxygenation, magnetic resonance imaging-determined brain growth, and 2-year neurodevelopmental outcome in a cohort of infants born preterm whose duct was closed surgically., Study Design: Infants born preterm at <30 weeks of gestational age who underwent surgical ductal closure between 2008 and 2018 (n = 106) were included in this observational study. Near infrared spectroscopy-monitored cerebral oxygen saturation during and up to 24 hours after ductal closure and a Bayley III developmental test at the corrected age of 2 years is the institutional standard of care for this patient group. Infants also had magnetic resonance imaging at term-equivalent age., Results: In total, 90 infants fulfilled the inclusion criteria (median [range]: 25.9 weeks [24.0-28.9]; 856 g [540-1350]. Days of a PDA ranged from 1 to 41. Multivariable linear regression analysis showed that duration of a PDA negatively influenced cerebellar growth and motor and cognitive outcome at 2 years of corrected age., Conclusions: Prolonged duration of a PDA in this surgical cohort is associated with reduced cerebellar growth and suboptimal neurodevelopmental outcome., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This prospective study evaluates our first clinical experiences with the novel ``BRachytherapy via artificial Intelligent GOMEA-Heuristic based Treatment planning'' (BRIGHT) applied to high-dose-rate prostate brachytherapy., Methods and Materials: Between March 2020 and October 2021, 14 prostate cancer patients were treated in our center with a 15Gy HDR-brachytherapy boost. BRIGHT was used for bi-objective treatment plan optimization and selection of the most desirable plans from a coverage-sparing trade-off curve. Selected BRIGHT plans were imported into the commercial treatment planning system Oncentra Brachy . In Oncentra Brachy a dose distribution comparison was performed for clinical plan choice, followed by manual fine-tuning of the preferred BRIGHT plan when deemed necessary. The reasons for plan selection, clinical plan choice, and fine-tuning, as well as process speed were monitored. For each patient, the dose-volume parameters of the (fine-tuned) clinical plan were evaluated., Results: In all patients, BRIGHT provided solutions satisfying all protocol values for coverage and sparing. In four patients not all dose-volume criteria of the clinical plan were satisfied after manual fine-tuning. Detailed information on tumour coverage, dose-distribution, dwell time pattern, and insight provided by the patient-specific trade-off curve, were used for clinical plan choice. Median time spent on treatment planning was 42 min, consisting of 16 min plan optimization and selection, and 26 min undesirable process steps., Conclusions: BRIGHT is implemented in our clinic and provides automated prostate high-dose-rate brachytherapy planning with trade-off based plan selection. Based on our experience, additional optimization aims need to be implemented to further improve direct clinical applicability of treatment plans and process efficiency., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Deformable image registration (DIR) can benefit from additional guidance using corresponding landmarks in the images. However, the benefits thereof are largely understudied, especially due to the lack of automatic landmark detection methods for three-dimensional (3D) medical images., Approach: We present a deep convolutional neural network (DCNN), called DCNN-Match, that learns to predict landmark correspondences in 3D images in a self-supervised manner. We trained DCNN-Match on pairs of computed tomography (CT) scans containing simulated deformations. We explored five variants of DCNN-Match that use different loss functions and assessed their effect on the spatial density of predicted landmarks and the associated matching errors. We also tested DCNN-Match variants in combination with the open-source registration software Elastix to assess the impact of predicted landmarks in providing additional guidance to DIR., Results: We tested our approach on lower abdominal CT scans from cervical cancer patients: 121 pairs containing simulated deformations and 11 pairs demonstrating clinical deformations. The results showed significant improvement in DIR performance when landmark correspondences predicted by DCNN-Match were used in the case of simulated ( p = 0 e 0 ) as well as clinical deformations ( p = 0.030 ). We also observed that the spatial density of the automatic landmarks with respect to the underlying deformation affect the extent of improvement in DIR. Finally, DCNN-Match was found to generalize to magnetic resonance imaging scans without requiring retraining, indicating easy applicability to other datasets., Conclusions: DCNN-match learns to predict landmark correspondences in 3D medical images in a self-supervised manner, which can improve DIR performance., (© 2023 The Authors.)

Antenatal assessment of congenital heart disease and associated anomalies by ultrasound has improved perinatal care. Fetal cardiovascular MRI and fetal brain MRI are rapidly evolving for fetal diagnostic testing of congenital heart disease. We give an overview on the use of fetal cardiovascular MRI and fetal brain MRI in congenital heart disease, focusing on the current applications and diagnostic yield of structural and functional imaging during pregnancy. Fetal cardiovascular MRI in congenital heart disease is a promising supplementary imaging method to echocardiography for the diagnosis of antenatal congenital heart disease in weeks 30-40 of pregnancy. Concomitant fetal brain MRI is superior to brain ultrasound to show the complex relationship between fetal haemodynamics in congenital heart disease and brain development., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Domination-based multiobjective (MO) evolutionary algorithms (EAs) are today arguably the most frequently used type of MOEA. These methods, however, stagnate when the majority of the population becomes nondominated, preventing further convergence to the Pareto set. Hypervolume-based MO optimization has shown promising results to overcome this. Direct use of the hypervolume, however, results in no selection pressure for dominated solutions. The recently introduced Sofomore framework overcomes this by solving multiple interleaved single-objective dynamic problems that iteratively improve a single approximation set, based on the uncrowded hypervolume improvement (UHVI). It thereby however loses many advantages of population-based MO optimization, such as handling multimodality. Here, we reformulate the UHVI as a quality measure for approximation sets, called the uncrowded hypervolume (UHV), which can be used to directly solve MO optimization problems with a single-objective optimizer. We use the state-of-the-art gene-pool optimal mixing evolutionary algorithm (GOMEA) that is capable of efficiently exploiting the intrinsically available grey-box properties of this problem. The resulting algorithm, UHV-GOMEA, is compared with Sofomore equipped with GOMEA, and the domination-based MO-GOMEA. In doing so, we investigate in which scenarios either domination-based or hypervolume-based methods are preferred. Finally, we construct a simple hybrid approach that combines MO-GOMEA with UHV-GOMEA and outperforms both., (© 2021 Massachusetts Institute of Technology.)

Objectives: Children with cancer often experience sleep problems, which are associated with many negative physical and psychological health outcomes, as well as with a lower quality of life. Therefore, interventions are strongly required to improve sleep in this population. We evaluated interactive education with respect to sleep hygiene with a social robot at a pediatric oncology outpatient clinic regarding the feasibility, experiences, and preliminary effectiveness., Methods: Researchers approached children (8 to 12 years old) who were receiving anticancer treatment and who were visiting the outpatient clinic with their parents during the two-week study period. The researchers completed observation forms regarding feasibility, and parents completed the Children's Sleep Hygiene Scale before and two weeks after the educational regimen. The experiences of children and parents were evaluated in semi-structured interviews. We analyzed open answers by labeling each answer with a topic reflecting the content and collapsed these topics into categories. We used descriptive statistics to describe the feasibility and experiences, and a dependent-samples t -test to evaluate the preliminary effectiveness., Results: Twenty-eight families participated (58% response rate) and all interactions with the robot were completed. The children and parents reported that they learned something new (75% and 50%, respectively), that they wanted to learn from the robot more often (83% and 75%, respectively), and that they applied the sleeping tips from the robot afterwards at home (54%). Regarding the preliminary effectiveness, children showed a statistically significant improvement in their sleep hygiene ( p = 0.047, d = 0.39)., Conclusions: Providing an educational regimen on sleep hygiene in a novel, interactive way by using a social robot at the outpatient clinic seemed feasible, and the children and parents mostly exhibited positive reactions. We found preliminary evidence that the sleep hygiene of children with cancer improved.

Purpose: Our purpose was to validate and compare the performance of 4 organ dose reconstruction approaches for historical radiation treatment planning based on 2-dimensional radiographs., Methods and Materials: We considered 10 patients with Wilms tumor with planning computed tomography images for whom we developed typical historic Wilms tumor radiation treatment plans, using anteroposterior and posteroanterior parallel-opposed 6 MV flank fields, normalized to 14.4 Gy. Two plans were created for each patient, with and without corner blocking. Regions of interest (lungs, heart, nipples, liver, spleen, contralateral kidney, and spinal cord) were delineated, and dose-volume metrics including organ mean and minimum dose (D mean and D min ) were computed as the reference baseline for comparison. Dosimetry for the 20 plans was then independently reconstructed using 4 different approaches. Three approaches involved surrogate anatomy, among which 2 used demographic-matching criteria for phantom selection/building, and 1 used machine learning. The fourth approach was also machine learning-based, but used no surrogate anatomies. Absolute differences in organ dose-volume metrics between the reconstructed and the reference values were calculated., Results: For D mean and D min (average and minimum point dose) all 4 dose reconstruction approaches performed within 10% of the prescribed dose (≤1.4 Gy). The machine learning-based approaches showed a slight advantage for several of the considered regions of interest. For D max (maximum point dose), the absolute differences were much higher, that is, exceeding 14% (2 Gy), with the poorest agreement observed for near-beam and out-of-beam organs for all approaches., Conclusions: The studied approaches give comparable dose reconstruction results, and the choice of approach for cohort dosimetry for late effects studies should still be largely driven by the available resources (data, time, expertise, and funding)., (© 2022 The Authors.)

It is well known nowadays that radioactivity can destroy the living cells it interacts with. It is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. However, since then, new techniques have been invented that make creative use of the same radioactivity properties of these sources for medical applications. Here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. In brachytherapy (BT), the radioactive sources are used for internal radiation treatment. Current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomography, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. Radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. Radioactive seed localization (RSL) is increasingly popular as an alternative tumor localization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemply the implementation of RSL in a clinic through our experiences at the Netherlands Cancer Institute.

Background: Multiple clinical conditions are associated with cerebral hypoxia/ischaemia and thereby an increased risk of hypoxic-ischaemic brain injury. Cerebral near-infrared spectroscopy monitoring (NIRS) is a tool to monitor brain oxygenation and perfusion, and the clinical uptake of NIRS has expanded over recent years. Specifically, NIRS is used in the neonatal, paediatric, and adult perioperative and intensive care settings. However, the available literature suggests that clinical benefits and harms of cerebral NIRS monitoring are uncertain. As rates of clinically significant hypoxic-ischaemic brain injuries are typically low, it is difficult for randomised clinical trials to capture a sufficiently large number of events to evaluate the clinical effect of cerebral NIRS monitoring, when focusing on specific clinical settings. The aim of this systematic review will be to evaluate the benefits and harms of clinical care with access to cerebral NIRS monitoring versus clinical care without cerebral NIRS monitoring in children and adults across all clinical settings., Methods: We will conduct a systematic review with meta-analysis and trial sequential analysis. We will only include randomised clinical trials. The primary outcomes are all-cause mortality, moderate or severe persistent cognitive or neurological deficit, and proportion of participants with one or more serious adverse events. We will search CENTRAL, EMBASE, MEDLINE, and the Science Citation Index Expanded from their inception and onwards. Two reviewers will independently screen all citations, full-text articles, and extract data. The risk of bias will be appraised using the Cochrane risk of bias tool version 2.0. If feasible, we will conduct both random-effects meta-analysis and fixed-effect meta-analysis of outcome data. Additional analysis will be conducted to explore the potential sources of heterogeneity (e.g. risk of bias, clinical setting)., Discussion: As we include trials across multiple clinical settings, there is an increased probability of reaching a sufficient information size. However, heterogeneity between the included trials may impair our ability to interpret results to specific clinical settings. In this situation, we may have to depend on subgroup analyses with inherent increased risks of type I and II errors., Systematic Review Registration: PROSPERO CRD42020202986 . This systematic review protocol has been submitted for registration in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/prospero) on the 12th of October 2020 and published on the 12th of November 2020 (registration ID CRD42020202986 ).

Background: Postmortem examinations frequently show cerebellar injury in infants with severe hypoxic-ischemic encephalopathy (HIE), while it is less well visible on MRI. The primary aim was to investigate the correlation between cerebellar apparent diffusion coefficient (ADC) values and histopathology in infants with HIE. The secondary aim was to compare ADC values in the cerebellum of infants with HIE and infants without brain injury., Methods: ADC values in the cerebellar vermis, hemispheres and dentate nucleus (DN) of (near-)term infants with HIE (n = 33) within the first week after birth were compared with neonates with congenital non-cardiac anomalies, normal postoperative MRIs and normal outcome (n = 22). Microglia/macrophage activation was assessed using CD68 and/or HLA-DR staining and Purkinje cell (PC) injury using H&E-stained slices. The correlation between ADC values and the histopathological measures was analyzed., Results: ADC values in the vermis (p = 0.021) and DN (p < 0.001) were significantly lower in infants with HIE compared to controls. ADC values in the cerebellar hemispheres were comparable. ADC values in the vermis were correlated with the number and percentage of normal PCs; otherwise ADC values and histology were not correlated., Conclusion: Histopathological injury in the cerebellum is common in infants with HIE. ADC values underestimate histopathological injury., Impact: ADC values might underestimate cerebellar injury in neonates with HIE. ADC values in the vermis and dentate nucleus of infants with HIE are lower compared to controls, but not in the cerebellar hemispheres. Abnormal ADC values are only found when cytotoxic edema is very severe. ADC values in the vermis are correlated with Purkinje cell injury in the vermis; furthermore, there were no correlations between ADC values and histopathological measures.

It is known that to achieve efficient scalability of an Evolutionary Algorithm (EA), dependencies (also known as linkage) must be properly taken into account during variation. In a Gray-Box Optimization (GBO) setting, exploiting prior knowledge regarding these dependencies can greatly benefit optimization. We specifically consider the setting where partial evaluations are possible, meaning that the partial modification of a solution can be efficiently evaluated. Such problems are potentially very difficult, for example, non-separable, multimodal, and multiobjective. The Gene-pool Optimal Mixing Evolutionary Algorithm (GOMEA) can effectively exploit partial evaluations, leading to a substantial improvement in performance and scalability. GOMEA was recently shown to be extendable to real-valued optimization through a combination with the real-valued estimation of distribution algorithm AMaLGaM. In this article, we definitively introduce the Real-Valued GOMEA (RV-GOMEA), and introduce a new variant, constructed by combining GOMEA with what is arguably the best-known real-valued EA, the Covariance Matrix Adaptation Evolution Strategies (CMA-ES). Both variants of GOMEA are compared to L-BFGS and the Limited Memory CMA-ES (LM-CMA-ES). We show that both variants of RV-GOMEA achieve excellent performance and scalability in a GBO setting, which can be orders of magnitude better than that of EAs unable to efficiently exploit the GBO setting.

Purpose: Recently, we introduced a bi-objective optimization approach based on dose-volume indices to automatically create clinically good HDR prostate brachytherapy plans. To calculate dose-volume indices, a reconstruction algorithm is used to determine the 3D organ shape from 2D contours, inevitably containing settings that influence the result. We augment the optimization approach to quickly find plans that are robust to differences in 3D reconstruction., Methods: Studied reconstruction settings were: interpolation between delineated organ contours, overlap between contours, and organ shape at the top and bottom contour. Two options for each setting yields 8 possible 3D organ reconstructions per patient, over which the robust model defines minimax optimization. For the original model, settings were based on our treatment planning system. Both models were tested on data of 26 patients and compared by re-evaluating selected optimized plans both in the original model (1 organ reconstruction, the difference determines the cost), and in the robust model (8 organ reconstructions, the difference determines the benefit)., Results: Robust optimization increased the run time from 3 to 6 min. The median cost for robust optimization as observed in the original model was -0.25% in the dose-volume indices with a range of [-0.01%, -1.03%]. The median benefit of robust optimization as observed in the robust model was 0.93% with a range of [0.19%, 4.16%]. For 4 patients, selected plans that appeared good when optimized in the original model, violated the clinical protocol with more than 1% when considering different settings. This was not the case for robustly optimized plans., Conclusions: Plans of high quality, irrespective of 3D organ reconstruction settings, can be obtained using our robust optimization approach. With its limited effect on total runtime, our approach therefore offers a way to account for dosimetry uncertainties that result from choices in organ reconstruction settings that is viable in clinical practice.