Low-Dimensional Stochastic Modeling of the Electrical Properties of Biological Tissues

Uncertainty quantification plays an important role in biomedical engineering as measurement data is often unavailable and literature data shows a wide variability. Using state-of-the-art methods one encounters difficulties when the number of random inputs is large. This is the case, e.g., when using composite Cole-Cole equations to model random electrical properties. It is shown how the number of parameters can be significantly reduced by the Karhunen-Loeve expansion. The low-dimensional random model is used to quantify uncertainties in the axon activation during deep brain stimulation. Numerical results for a Medtronic 3387 electrode design are given.Comment: 4 pages, 5 figure

Dermatofibrosarcoma protuberans: Surgical excision versus Mohs surgery

The purpose of this project was to compare the recurrence rates of dermatofibrsarcoma protuberans (DFSP) treated with surgical excision (SE) and Mohs surgery (MS) at Yale. Patients were identified through the dermatopathology laboratory database and stratified by treatment. The following information was collected: age at onset, sex, disease state (primary presentation versus recurrence), tumor site, preoperative tumor size, postoperative defect size, excisional margin, duration of follow-up, and recurrence after treatment. Of the 30 patients, 14 were in the SE group, and 16 were in the MS group. There were no recurrences in the SE group, and there was 1 recurrence (6%) in the MS group, which occurred 37 months post-operatively. The average area of the tumors were 12.1 cm2 ± 16.1 (SE) and 5.3 cm2 ± 5.9 (MS), and the mean excisional margins were 3.8 cm ± 1.6 (SE) and 1.4 cm± 0.5 (MS). The mean duration of follow-up in the SE group was 33 months ± 41 (range: 1-116 months), and the mean duration of follow-up in the MS group was 26 months ± 25 (range: 2 to 69 months.) Although the MS group had a higher recurrence rate than the SE group, using the recurrence rates to make meaningful conclusions about the efficacy of the two treatment modalities is limited by the small n, lack of randomization to either procedure, and duration of follow-up. Once these issues are addressed, recurrence rates must also be adjusted for patient and tumor characteristics, that are associated with higher recurrence rates

Adhesion of osteoblasts to a nanorough titanium implant surface

This work considers the adhesion of cells to a nanorough titanium implant surface with sharp edges. The basic assumption was that the attraction between the negatively charged titanium surface and a negatively charged osteoblast is mediated by charged proteins with a distinctive quadrupolar internal charge distribution. Similarly, cation-mediated attraction between fibronectin molecules and the titanium surface is expected to be more efficient for a high surface charge density, resulting in facilitated integrin mediated osteoblast adhesion. We suggest that osteoblasts are most strongly bound along the sharp convex edges or spikes of nanorough titanium surfaces where the magnitude of the negative surface charge density is the highest. It is therefore plausible that nanorough regions of titanium surfaces with sharp edges and spikes promote the adhesion of osteoblasts

Uncertainty Modeling and Analysis of the European X-ray Free Electron Laser Cavities Manufacturing Process

This paper reports on comprehensive efforts on uncertainty quantification and global sensitivity analysis for accelerator cavity design. As a case study object the TESLA shaped superconducting cavities, as produced for the European X-ray Free Electron Laser (EXFEL), are selected. The choice for these cavities is explained by the available measurement data that can be leveraged to substantiate the simulation model. Each step of the manufacturing chain is documented together with the involved uncertainties. Several of these steps are mimicked on the simulation side, e.g. by introducing a random eigenvalue problem. The uncertainties are then quantified numerically and in particular the sensitivities give valuable insight into the systems behavior. We also compare these findings to purely statistical studies carried out for the manufactured cavities. More advanced, adaptive, surrogate modeling techniques are adopted, which are crucial to incorporate a large number of uncertain parameters. The main contribution is the detailed comparison and fusion of measurement results for the EXFEL cavities on the one hand and simulation based uncertainty studies on the other hand. After introducing the quantities of physical interest for accelerator cavities and the Maxwell eigenvalue problem, the details on the manufacturing of the EXFEL cavities and measurements are reported. This is followed by uncertainty modeling with quantification studies

Long-term stimulation with alternating electric fields modulates the differentiation and mineralization of human pre-osteoblasts

Biophysical stimulation by electric fields can promote bone formation in bone defects of critical size. Even though, long-term effects of alternating electric fields on the differentiation of osteoblasts are not fully understood. Human pre-osteoblasts were stimulated over 31 days to gain more information about these cellular processes. An alternating electric field with 0.7 Vrms and 20 Hz at two distances was applied and viability, mineralization, gene expression, and protein release of differentiation factors were analyzed. The viability was enhanced during the first days of stimulation. A higher electric field resulted in upregulation of typical osteogenic markers like osteoprotegerin, osteopontin, and interleukin-6, but no significant changes in mineralization. Upregulation of the osteogenic markers could be detected with a lower electric field after the first days of stimulation. As a significant increase in the mineralized matrix was identified, an enhanced osteogenesis due to low alternating electric fields can be assumed

Discrimination between the effects of pulsed electrical stimulation and electrochemically conditioned medium on human osteoblasts

Background Electrical stimulation is used for enhanced bone fracture healing. Electrochemical processes occur during the electrical stimulation at the electrodes and influence cellular reactions. Our approach aimed to distinguish between electrochemical and electric field effects on osteoblast-like MG-63 cells. We applied 20 Hz biphasic pulses via platinum electrodes for 2 h. The electrical stimulation of the cell culture medium and subsequent application to cells was compared to directly stimulated cells. The electric field distribution was predicted using a digital twin. Results Cyclic voltammetry and electrochemical impedance spectroscopy revealed partial electrolysis at the electrodes, which was confirmed by increased concentrations of hydrogen peroxide in the medium. While both direct stimulation and AC-conditioned medium decreased cell adhesion and spreading, only the direct stimulation enhanced the intracellular calcium ions and reactive oxygen species. Conclusion The electrochemical by-product hydrogen peroxide is not the main contributor to the cellular effects of electrical stimulation. However, undesired effects like decreased adhesion are mediated through electrochemical products in stimulated medium. Detailed characterisation and monitoring of the stimulation set up and electrochemical reactions are necessary to find safe electrical stimulation protocols.Open Access funding enabled and organized by Projekt DEAL. This research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), grant number SFB ELAINE, 1270/1,2–299150580. We also acknowledge the funding from Atracción de Talento Programme, Modalidad‑1 Ref. 2019‑T1/IND‑1335 and the grant PID2021‑128611OB‑I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe.Peer reviewe

Lead-DBS v3.0: Mapping Deep Brain Stimulation Effects to Local Anatomy and Global Networks.

Following its introduction in 2014 and with support of a broad international community, the open-source toolbox Lead-DBS has evolved into a comprehensive neuroimaging platform dedicated to localizing, reconstructing, and visualizing electrodes implanted in the human brain, in the context of deep brain stimulation (DBS) and epilepsy monitoring. Expanding clinical indications for DBS, increasing availability of related research tools, and a growing community of clinician-scientist researchers, however, have led to an ongoing need to maintain, update, and standardize the codebase of Lead-DBS. Major development efforts of the platform in recent years have now yielded an end-to-end solution for DBS-based neuroimaging analysis allowing comprehensive image preprocessing, lead localization, stimulation volume modeling, and statistical analysis within a single tool. The aim of the present manuscript is to introduce fundamental additions to the Lead-DBS pipeline including a deformation warpfield editor and novel algorithms for electrode localization. Furthermore, we introduce a total of three comprehensive tools to map DBS effects to local, tract- and brain network-levels. These updates are demonstrated using a single patient example (for subject-level analysis), as well as a retrospective cohort of 51 Parkinson's disease patients who underwent DBS of the subthalamic nucleus (for group-level analysis). Their applicability is further demonstrated by comparing the various methodological choices and the amount of explained variance in clinical outcomes across analysis streams. Finally, based on an increasing need to standardize folder and file naming specifications across research groups in neuroscience, we introduce the brain imaging data structure (BIDS) derivative standard for Lead-DBS. Thus, this multi-institutional collaborative effort represents an important stage in the evolution of a comprehensive, open-source pipeline for DBS imaging and connectomics