Electrical stimulation of the nucleus basalis of meynert:a systematic review of preclinical and clinical data

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been clinically investigated in Alzheimer's disease (AD) and Lewy body dementia (LBD). However, the clinical effects are highly variable, which questions the suggested basic principles underlying these clinical trials. Therefore, preclinical and clinical data on the design of NBM stimulation experiments and its effects on behavioral and neurophysiological aspects are systematically reviewed here. Animal studies have shown that electrical stimulation of the NBM enhanced cognition, increased the release of acetylcholine, enhanced cerebral blood flow, released several neuroprotective factors, and facilitates plasticity of cortical and subcortical receptive fields. However, the translation of these outcomes to current clinical practice is hampered by the fact that mainly animals with an intact NBM were used, whereas most animals were stimulated unilaterally, with different stimulation paradigms for only restricted timeframes. Future animal research has to refine the NBM stimulation methods, using partially lesioned NBM nuclei, to better resemble the clinical situation in AD, and LBD. More preclinical data on the effect of stimulation of lesioned NBM should be present, before DBS of the NBM in human is explored further

Схеми скорочення необхідного об'єму вимірювань у методі контролю стаціонарної підйомної установки

Предлагается последовательная процедура принятия решения относительно вектора характеристик контролируемой стационарной подъемной установки, которая является некоторым обобщением процедуры Вальда и позволяет получить выигрыш в среднем объеме испытаний, аналогичный обычному «вальдовскому» выигрышу для случая двух гипотез. Предлагаемая последовательная процедура позволяет учитывать дополнительную информацию и за счет этого получить добавочный выигрыш в объеме контроля стационарной подъемной установки.Offers a consistent decision-making procedure for the vector characteristics of the controlled stationary hoist, which is a generalization of Wald's procedure and provides a gain in the average volume of tests, similar to the usual "of Wald's" winning the case of two hypotheses. The proposed sequential procedure takes into account the additional information and thereby obtain additional gains in the amount of control a stationary hoist

Using Intratumor Heterogeneity of Immunohistochemistry Biomarkers to Classify Laryngeal and Hypopharyngeal Tumors Based on Histologic Features

Haralick texture features are used to quantify the spatial distribution of signal intensities within an image. In this study, the heterogeneity of proliferation (Ki-67 expression) and immune cells (CD45 expression) within tumors was quantified and used to classify histologic characteristics of larynx and hypopharynx carcinomas. Of 21 laryngectomy specimens, 74 whole-mount tumor slides were scored on histologic characteristics. Ki-67 and CD45 immunohistochemistry was performed, and all sections were digitized. The tumor area was annotated in QuPath. Haralick features independent of the diaminobenzidine intensity were extracted from the isolated diaminobenzidine signal to quantify intratumor heterogeneity. Haralick features from both Ki-67 and CD45 were used as input for a principal component analysis. A linear support vector machine was fitted to the first 4 principal components for classification and validated with a leave-one-patient-out cross-validation method. Significant differences in individual Haralick features were found between cohesive and noncohesive tumors for CD45 (angular second motion: P =.03, inverse difference moment: P =.009, and entropy: P =.02) and between the larynx and hypopharynx tumors for both CD45 (angular second motion: P =.03, inverse difference moment: P =.007, and entropy: P =.005) and Ki-67 (correlation: P =.003). Therefore, these features were used for classification. The linear classifier resulted in a classification accuracy of 85% for site of origin and 81% for growth pattern. A leave-one-patient-out cross-validation resulted in an error rate of 0.27 and 0.35 for both classifiers, respectively. In conclusion, we show a method to quantify intratumor heterogeneity of immunohistochemistry biomarkers using Haralick features. This study also shows the feasibility of using these features to classify tumors by histologic characteristics. The classifiers created in this study are a proof of concept because more data are needed to create robust classifiers, but the method shows potential for automated tumor classification.</p

Correlation and colocalization of HIF-1a and pimonidazole staining for hypoxia in laryngeal squamous cell carcinomas:A digital, single-cell-based analysis

OBJECTIVE: Tumor hypoxia results in worse local control and patient survival. We performed a digital, single-cell-based analysis to compare two biomarkers for hypoxia (hypoxia-inducible factor 1-alpha [HIF-1α] and pimonidazole [PIMO]) and their effect on outcome in laryngeal cancer patients treated with accelerated radiotherapy with or without carbogen breathing and nicotinamide (AR versus ARCON). MATERIALS AND METHODS: Immunohistochemical staining was performed for HIF-1α and PIMO in consecutive sections of 44 laryngeal cancer patients randomized between AR and ARCON. HIF-1α expression and PIMO-binding were correlated using digital image analysis in QuPath. High-density areas for each biomarker were automatically annotated and staining overlap was analyzed. Kaplan-Meier survival analyses for local control, regional control and disease-free survival were performed to predict a response benefit of ARCON over AR alone for each biomarker. RESULTS: 106 Tissue fragments of 44 patients were analyzed. A weak, significant positive correlation was observed between HIF-1α and PIMO positivity on fragment level, but not on patient level. A moderate strength correlation (r = 0.705, p < 0.001) was observed between the number of high-density staining areas for both biomarkers. Staining overlap was poor. HIF-1α expression, PIMO-binding or a combination could not predict a response benefit of ARCON over AR. CONCLUSION: Digital image analysis to compare positive cell fractions and staining overlap between two hypoxia biomarkers using open-source software is feasible. Our results highlight that there are distinct differences between HIF-1α and PIMO as hypoxia biomarkers and therefore suggest co-existence of different forms of hypoxia within a single tumor

Physics of IED Blast Shock Tube Simulations for mTBI Research

Shock tube experiments and simulations are conducted with a spherical gelatin filled skull–brain surrogate, in order to study the mechanisms leading to blast induced mild traumatic brain injury. A shock tube including sensor system is optimized to simulate realistic improvised explosive device blast profiles obtained from full scale field tests. The response of the skull–brain surrogate is monitored using pressure and strain measurements. Fluid–structure interaction is modeled using a combination of computational fluid dynamics (CFD) simulations for the air blast, and a finite element model for the structural response. The results help to understand the physics of wave propagation, from air blast into the skull–brain. The presence of openings on the skull and its orientation does have a strong effect on the internal pressure. A parameter study reveals that when there is an opening in the skull, the skull gives little protection and the internal pressure is fairly independent on the skull stiffness; the gelatin shear stiffness has little effect on the internal pressure. Simulations show that the presence of pressure sensors in the gelatin hardly disturbs the pressure field

Multi-modal volumetric concept activation to explain detection and classification of metastatic prostate cancer on PSMA-PET/CT

Explainable artificial intelligence (XAI) is increasingly used to analyze the behavior of neural networks. Concept activation uses human-interpretable concepts to explain neural network behavior. This study aimed at assessing the feasibility of regression concept activation to explain detection and classification of multi-modal volumetric data. Proof-of-concept was demonstrated in metastatic prostate cancer patients imaged with positron emission tomography/computed tomography (PET/CT). Multi-modal volumetric concept activation was used to provide global and local explanations. Sensitivity was 80% at 1.78 false positive per patient. Global explanations showed that detection focused on CT for anatomical location and on PET for its confidence in the detection. Local explanations showed promise to aid in distinguishing true positives from false positives. Hence, this study demonstrated feasibility to explain detection and classification of multi-modal volumetric data using regression concept activation.Comment: Accepted as: Kraaijveld, R.C.J., Philippens, M.E.P., Eppinga, W.S.C., J\"urgenliemk-Schulz, I.M., Gilhuijs, K.G.A., Kroon, P.S., van der Velden, B.H.M. "Multi-modal volumetric concept activation to explain detection and classification of metastatic prostate cancer on PSMA-PET/CT." MICCAI workshop on Interpretability of Machine Intelligence in Medical Image Computing (iMIMIC), 202

Association of histological features with laryngeal squamous cell carcinoma recurrences:a population-based study of 1502 patients in the Netherlands

BACKGROUND: Recurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival. MATERIAL AND METHODS: Demographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010–2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis. RESULTS: In total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68–1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63–3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48–4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found. CONCLUSION: In this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09533-0

Redefining radiotherapy for early-stage breast cancer with single dose ablative treatment: a study protocol

Contains fulltext : 181789.pdf (publisher's version ) (Open Access

Brain and Head-and-Neck MRI in Immobilization Mask: A Practical Solution for MR-Only Radiotherapy

In brain/head-and-neck radiotherapy (RT), thermoplastic immobilization masks guarantee reproducible patient positioning in treatment position between MRI, CT, and irradiation. Since immobilization masks do not fit in the diagnostic MR head/head-and-neck coils, flexible surface coils are used for MRI imaging in clinical practice. These coils are placed around the head/neck, in contact with the immobilization masks. However, the positioning of these flexible coils is technician dependent, thus leading to poor image reproducibility. Additionally, flexible surface coils have an inferior signal-to-noise-ratio (SNR) compared to diagnostic coils. The aim of this work was to create a new immobilization setup which fits into the diagnostic MR coils in order to enhance MR image quality and reproducibility. For this purpose, a practical immobilization setup was constructed. The performances of the standard clinical and the proposed setups were compared with four tests: SNR, image quality, motion restriction, and reproducibility of inter-fraction subject positioning. The new immobilization setup resulted in 3.4 times higher SNR values on average than the standard setup, except directly below the flexible surface coils where similar SNR was observed. Overall, the image quality was superior for brain/head-and-neck images acquired with the proposed RT setup. Comparable motion restriction in feet-head/left-right directions (maximum motion ≈1 mm) and comparable inter-fraction repositioning accuracy (mean inter-fraction movement 1 ± 0.5 mm) were observed for the standard and the new setup

Unmappable ventricular tachycardia after an old myocardial infarction. Long-term results of substrate modification in patients with an implantable cardioverter defibrillator

Purpose The frequent occurrence of ventricular tachycardia can create a serious problem in patients with an implantable cardioverter defibrillator. We assessed the long-term efficacy of catheter-based substrate modification using the voltage mapping technique of infarct-related ventricular tachycardia and recurrent device therapy. Methods The study population consisted of 27 consecutive patients (age 68 +/- 8 years, 25 men, mean left ventricular ejection fraction 31 +/- 9%) with an old myocardial infarction and multiple and/or hemodynamically not tolerated ventricular tachycardia necessitating repeated device therapy. A total of 31 substrate modification procedures were performed using the three-dimensional electroanatomical mapping system. Patients were followed up for a median of 23.5 (interquartile range 6.5-53.2) months before and 37.8 (interquartile range 11.7-71.8) months after ablation. Antiarrhythmic drugs were not changed after the procedure, and were stopped 6 to 9 months after the procedure in patients who did not show ventricular tachycardia recurrence. Results Median ventricular tachycardias were 1.6 (interquartile range 0.7-6.7) per month before and 0.2 (interquartile range 0.00-1.3) per month after ablation (P = 0.006). Nine ventricular fibrillation episodes were registered in seven patients before and two after ablation (P = 0.025). Median antitachycardia pacing decreased from 1.6 (interquartile range 0.01-5.5) per month before to 0.18 (interquartile range 0.00-1.6) per month after ablation (P = 0.069). Median number of shocks decreased from 0.19 (interquartile range 0.04-0.81) per month before to 0.00 (interquartile range 0.00-0.09) per month after ablation (P = 0.001). One patient had a transient ischemic attack during the procedure, and another developed pericarditis. Nine patients died during follow-up, eight patients due to heart failure and one patient during valve surgery. Conclusion Catheter-based substrate modification using voltage mapping results in a long-lasting reduction of cardioverter defibrillator therapy in patients with multiple and/or hemodynamically not tolerated infarct-related ventricular tachyarrhythmia