Bridging imaging users to imaging analysis - A community survey.

The 'Bridging Imaging Users to Imaging Analysis' survey was conducted in 2022 by the Center for Open Bioimage Analysis (COBA), BioImaging North America (BINA) and the Royal Microscopical Society Data Analysis in Imaging Section (RMS DAIM) to understand the needs of the imaging community. Through multichoice and open-ended questions, the survey inquired about demographics, image analysis experiences, future needs and suggestions on the role of tool developers and users. Participants of the survey were from diverse roles and domains of the life and physical sciences. To our knowledge, this is the first attempt to survey cross-community to bridge knowledge gaps between physical and life sciences imaging. Survey results indicate that respondents' overarching needs are documentation, detailed tutorials on the usage of image analysis tools, user-friendly intuitive software, and better solutions for segmentation, ideally in a format tailored to their specific use cases. The tool creators suggested the users familiarise themselves with the fundamentals of image analysis, provide constant feedback and report the issues faced during image analysis while the users would like more documentation and an emphasis on tool friendliness. Regardless of the computational experience, there is a strong preference for 'written tutorials' to acquire knowledge on image analysis. We also observed that the interest in having 'office hours' to get an expert opinion on their image analysis methods has increased over the years. The results also showed less-than-expected usage of online discussion forums in the imaging community for solving image analysis problems. Surprisingly, we also observed a decreased interest among the survey respondents in deep/machine learning despite the increasing adoption of artificial intelligence in biology. In addition, the community suggests the need for a common repository for the available image analysis tools and their applications. The opinions and suggestions of the community, released here in full, will help the image analysis tool creation and education communities to design and deliver the resources accordingly.

Bridging Imaging Users to Imaging Analysis - A community survey.

The "Bridging Imaging Users to Imaging Analysis" survey was conducted in 2022 by the Center for Open Bioimage Analysis (COBA), Bioimaging North America (BINA), and the Royal Microscopical Society Data Analysis in Imaging Section (RMS DAIM) to understand the needs of the imaging community. Through multi-choice and open-ended questions, the survey inquired about demographics, image analysis experiences, future needs, and suggestions on the role of tool developers and users. Participants of the survey were from diverse roles and domains of the life and physical sciences. To our knowledge, this is the first attempt to survey cross-community to bridge knowledge gaps between physical and life sciences imaging. Survey results indicate that respondents' overarching needs are documentation, detailed tutorials on the usage of image analysis tools, user-friendly intuitive software, and better solutions for segmentation, ideally in a format tailored to their specific use cases. The tool creators suggested the users familiarize themselves with the fundamentals of image analysis, provide constant feedback, and report the issues faced during image analysis while the users would like more documentation and an emphasis on tool friendliness. Regardless of the computational experience, there is a strong preference for 'written tutorials' to acquire knowledge on image analysis. We also observed that the interest in having 'office hours' to get an expert opinion on their image analysis methods has increased over the years. In addition, the community suggests the need for a common repository for the available image analysis tools and their applications. The opinions and suggestions of the community, released here in full, will help the image analysis tool creation and education communities to design and deliver the resources accordingly.

Impact of and Response to Cyberattacks in Radiation Oncology.

Cyberattacks on health care facilities are increasing and significantly affecting health care delivery throughout the world. The recent cyberattack on our hospital-based radiation facility exposed vulnerabilities of radiation oncology systems and highlighted the dependence of radiation treatment on integrated and complex radiation planning, delivery and verification systems. After the cyberattack on our health care facility, radiation oncology staff reconstructed patient information, schedules, and radiation plans from existing paper records and physicians developed a system to triage patients requiring immediate transfer of radiation treatment to nearby facilities. Medical physics and hospital information technology collaborated to restore services without access to the system backup or network connectivity. Ultimately, radiation treatments resumed incrementally as systems were restored and rebuilt. The experiences and lessons learned from this response were reviewed. The successes and shortcomings were incorporated into recommendations to provide guidance to other radiation facilities in preparation for a possible cyberattack. Our response and recommendations are intended to serve as a starting point to assist other facilities in cybersecurity preparedness planning. Because there is no one-size-fits-all response, each department should determine its specific vulnerabilities, risks, and available resources to create an individualized plan.

Ultrasound for the Objective Measurement of Breast Lymphedema.

OBJECTIVES: Breast lymphedema has supplanted upper extremity lymphedema as a common and debilitating sequela of breast cancer treatment, but has no objective measurement. We assessed the utility of ultrasound-measured difference in dermal thickness between affected and unaffected breasts as a measure of breast lymphedema. We associated this measure with patient characteristics, treatment parameters, and patient-reported impact on quality of life. METHODS: We enrolled 30 invasive breast carcinoma patients treated with breast-conserving surgery, sentinel lymph node biopsy, and radiotherapy, and 10 control patients evaluated for benign breast conditions without prior breast surgery or radiotherapy. Patient and treatment variables were ascertained from medical records and radiotherapy instruments. Impacts on quality of life were measured with a modified Disability of the Arm, Shoulder, and Hand questionnaire. We characterized breast lymphedema by calculating the difference in ultrasound-measured dermal thickness between affected and unaffected breasts. Associations with patient characteristics, treatment, and quality of life were quantified with log-binomial regression models. RESULTS: Breast lymphedema was defined as a dermal thickness difference of >0.3 mm. Nineteen patients in the invasive group (63%) had breast lymphedema by this definition. We observed positive associations between ultrasound-defined breast lymphedema and surgical factors (size of primary tumor, number of lymph nodes removed), radiotherapy factors (breast volume irradiated, receipt of radiation boost), and patient-reported outcomes (sleep quality and overall confidence). CONCLUSIONS: Difference in dermal thickness is an easy and inexpensive measurement for quantifying breast lymphedema, and correlates with treatment parameters and patient-reported impacts on quality of life.

Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model.

PURPOSE: The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). METHODS: We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). RESULTS: For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. CONCLUSION: We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.

Asthma and obesity: endotoxin another insult to add to injury?

Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.

Neuronal Graphs: A Graph Theory Primer for Microscopic, Functional Networks of Neurons Recorded by Calcium Imaging.

Connected networks are a fundamental structure of neurobiology. Understanding these networks will help us elucidate the neural mechanisms of computation. Mathematically speaking these networks are "graphs"-structures containing objects that are connected. In neuroscience, the objects could be regions of the brain, e.g., fMRI data, or be individual neurons, e.g., calcium imaging with fluorescence microscopy. The formal study of graphs, graph theory, can provide neuroscientists with a large bank of algorithms for exploring networks. Graph theory has already been applied in a variety of ways to fMRI data but, more recently, has begun to be applied at the scales of neurons, e.g., from functional calcium imaging. In this primer we explain the basics of graph theory and relate them to features of microscopic functional networks of neurons from calcium imaging-neuronal graphs. We explore recent examples of graph theory applied to calcium imaging and we highlight some areas where researchers new to the field could go awry.

Assessing Laparoscopic Surgical Skills Using Similarity Network Models: A Pilot Study.

Background: Medical devices are becoming more complex, and doctors need to learn quickly how to use new medical tools. However, it is challenging to objectively assess the fundamental laparoscopic surgical skill level and determine skill readiness for advancement. There is a lack of objective models to compare performance between medical trainees and experienced doctors. Methods: This article discusses the use of similarity network models for individual tasks and a combination of tasks to show the level of similarity between residents and medical students while performing each task and their overall laparoscopic surgical skill level using a medical device (eg laparoscopic instruments). When a medical student is connected to most residents, that student is competent to the next training level. Performance of sixteen participants (5 residents and 11 students) while performing 3 tasks in 3 different training schedules is used in this study. Results: The promising result shows the general positive progression of students over 4 training sessions. Our results also indicate that students with different training schedules have different performance levels. Students' progress in performing a task is quicker if the training sessions are held more closely compared to when the training sessions are far apart in time. Conclusions: This study provides a graph-based framework for evaluating new learners' performance on medical devices and their readiness for advancement. This similarity network method could be used to classify students' performance using similarity thresholds, facilitating decision-making related to training and progression through curricula.

The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.

PURPOSE: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. METHODS: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. RESULTS: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (ß = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (ß = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (ß = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure. CONCLUSION: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

New horizons from novel therapies in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.

Author Correction: Adaptive prospective optical gating enables day-long 3D time-lapse imaging of the beating embryonic zebrafish heart.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Walking with added mass magnifies salient features of human foot energetics.

The human foot serves numerous functional roles during walking, including shock absorption and energy return. Here, we investigated walking with added mass to determine how the foot would alter its mechanical work production in response to a greater force demand. Twenty-one healthy young adults walked with varying levels of added body mass: 0%, +15% and +30% (relative to their body mass). We quantified mechanical work performed by the foot using a unified deformable segment analysis and a multi-segment foot model. We found that walking with added mass tended to magnify certain features of the foot's functions. Magnitudes of both positive and negative mechanical work, during stance in the foot, increased when walking with added mass. Yet, the foot preserved similar amounts of net negative work, indicating that the foot dissipates energy overall. Furthermore, walking with added mass increased the foot's negative work during early stance phase, highlighting the foot's role as a shock-absorber. During mid to late stance, the foot produced greater positive work when walking with added mass, which coincided with greater work from the structures spanning the midtarsal joint (i.e. arch). While this study captured the overall behavior of the foot when walking with varying force demands, future studies are needed to further determine the relative contribution of active muscles and elastic tissues to the foot's overall energy.

The multiscale top-hat tensor enables specific enhancement of curvilinear structures in 2D and 3D images.

Quantification and modelling of curvilinear structures in 2D and 3D images is a common challenge in a wide range of biomedical applications. Image enhancement is a crucial pre-processing step for curvilinear structure quantification. Many of the existing state-of-the-art enhancement approaches still suffer from contrast variations and noise. In this paper, we propose to address such problems via the use of a multiscale image processing approach, called Multiscale Top-Hat Tensor (MTHT). MTHT produces a better quality enhancement of curvilinear structures in low contrast and noisy images compared with other approaches in a range of 2D and 3D biomedical images. The proposed approach combines multiscale morphological filtering with a local tensor representation of curvilinear structure. The MTHT approach is validated on 2D and 3D synthetic and real images, and is also compared to the state-of-the-art curvilinear structure enhancement approaches. The obtained results demonstrate that the proposed approach provides high-quality curvilinear structure enhancement, allowing high accuracy segmentation and quantification in a wide range of 2D and 3D image datasets.

Identification of a subset of trace amine-associated receptors and ligands as potential modulators of insulin secretion.

The worldwide prevalence of diabetes has reached 8.5% among adults, and this is characterised by elevated glucose concentrations and failing insulin secretion. Furthermore, most people with type 2 diabetes are either obese or overweight, with the associated dyslipidaemia contributing to the development of insulin resistance and increased cardiovascular risk. Here we incubated INS-1 pancreatic ß-cells for 72 h in RPMI-1640 media, or media supplemented with 28 mM glucose, 200 µM palmitic acid, and 200 µM oleic acid as a cellular model of diabetic glucolipotoxicity. Illumina HiSeq gene expression analysis showed the trace amine-associated receptor (TAAR) family to be among the most highly downregulated by glucolipotoxicity. Importantly, MetaCore integrated knowledge database, from Clarivate Analytics, indicated potential TAAR impact on insulin secretion through adenylyl cyclase signalling pathways. We therefore investigated the effect of TAAR ligands on cAMP signalling and insulin secretion, and found that only the branch of the TAAR family tree that is activated by isopentylamine, 2-phenylethylamine, p-tyramine, and agmatine significantly increased intracellular cAMP and resulted in increased insulin secretion from INS-1 cells and primary mouse islets under normal conditions. Crucially however, this enhancement was not evident when the receptor family was downregulated by glucolipotoxic conditions. This data indicates that a subset of TAARs are regulators of insulin secretion in pancreatic ß-cells, and that their downregulation contributes to glucolipotoxic inhibition of insulin secretion. As such they may be potential targets for treatment of type 2 diabetes.

Adaptive prospective optical gating enables day-long 3D time-lapse imaging of the beating embryonic zebrafish heart.

Three-dimensional fluorescence time-lapse imaging of the beating heart is extremely challenging, due to the heart's constant motion and a need to avoid pharmacological or phototoxic damage. Although real-time triggered imaging can computationally "freeze" the heart for 3D imaging, no previous algorithm has been able to maintain phase-lock across developmental timescales. We report a new algorithm capable of maintaining day-long phase-lock, permitting routine acquisition of synchronised 3D + time video time-lapse datasets of the beating zebrafish heart. This approach has enabled us for the first time to directly observe detailed developmental and cellular processes in the beating heart, revealing the dynamics of the immune response to injury and witnessing intriguing proliferative events that challenge the established literature on cardiac trabeculation. Our approach opens up exciting new opportunities for direct time-lapse imaging studies over a 24-hour time course, to understand the cellular mechanisms underlying cardiac development, repair and regeneration.

A sensorless force-feedback system for robot-assisted laparoscopic surgery.

The existing surgical robots for laparoscopic surgery offer no or limited force feedback, and there are many problems for the traditional sensor-based solutions. This paper builds a teleoperation surgical system and validates the effectiveness of sensorless force feedback. The tool-tissue interaction force at the surgical grasper tip is estimated using the driving motor's current, and fed back to the master robot with position-force bilateral control algorithm. The stiffness differentiation experiment and tumor detection experiment were conducted. In the stiffness differentiation experiment, 43 out of 45 pairs of ranking relationships were identified correctly, yielding a success rate of 96%. In the tumor detection experiment, 4 out of 5 participants identified the correct tumor location with force feedback, yielding a success rate of 80%. The proposed sensorless force-feedback system for robot-assisted laparoscopic surgery can help surgeons regain tactile information and distinguish between the healthy and cancerous tissue.

Daily localization of partial breast irradiation patients with three-dimensional ultrasound imaging.

PURPOSE: Accurate localization of the lumpectomy cavity during accelerated partial breast radiation (APBR) is essential for daily setup to ensure the prescribed dose encompasses the target and avoids unnecessary irradiation to surrounding normal tissues. Three-dimensional ultrasound (3D-US) allows direct visualization of the lumpectomy cavity without additional radiation exposure. The purpose of this study was to evaluate the feasibility of 3D-US in daily target localization for APBR. MATERIALS AND METHODS: Forty-seven patients with stage I breast cancer who underwent breast conserving surgery were treated with a 2-week course of APBR. Patients with visible lumpectomy cavities on high quality 3D-US images were included in this analysis. Prior to each treatment, X-ray and 3D-US images were acquired and compared to images from simulation to confirm accurate position and determine shifts. Volume change of the lumpectomy cavity was determined daily with 3D-US. RESULTS: A total of 118 images of each modality from 12 eligible patients were analyzed. The average change in cavity volume was 7.8% (range, -24.1% to 14.4%) on 3D-US from simulation to the end-of-treatment. Based on 3D-US, significantly larger shifts were necessary compared to portal films in all three dimensions: anterior/posterior (p = 7E-11), left/right (p = 0.002), and superior/inferior (p = 0.004). CONCLUSION: Given that the lumpectomy cavity is not directly visible via X-ray images, accurate positioning may not be fully achieved by X-ray images. Therefore, when the lumpectomy cavity is visible on US, 3D-US can be considered as an alternative to X-ray imaging during daily positioning for selected patients treated with APBR, thus avoiding additional exposure to ionizing radiation.