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A year-long design project is a typical requirement for an undergraduate engineering degree. However, the abbreviated, two-semester format limits most projects from reaching appropriate maturity for obtaining intellectual property (IP) protection, external funding, and/or peer-reviewed publications. The traditional model may be associated with some dissatisfaction with the abrupt ending of the work, as projects are often just completing their initial proof-of-concept testing after 1 year. This study reports the results of a pilot experiment that allowed such design projects to extend through a second year. We investigated three different mechanisms for continuation: research credits, a second-year curricular course (Advanced Design Teams), and extracurricular support. Students in this program continued to engage with an advisory board of clinicians, engineers, and other professionals, many of whom had assisted with the project during the first year. We investigated whether continuing the projects in a curricular fashion may provide a better avenue for productivity than extracurricular mechanisms. Based on the results of this pilot study, our department has formalized a curriculum to support teams beyond the first year, in which continuing students from the first-year teams can apply to continue their projects for credit toward their degrees.

While deep learning has catalyzed breakthroughs across numerous domains, its broader adoption in clinical settings is inhibited by the costly and time-intensive nature of data acquisition and annotation. To further facilitate medical machine learning, we present an ultrasound dataset of 10,223 brightness-mode (B-mode) images consisting of sagittal slices of porcine spinal cords (N = 25) before and after a contusion injury. We additionally benchmark the performance metrics of several state-of-the-art object detection algorithms to localize the site of injury and semantic segmentation models to label the anatomy for comparison and creation of task-specific architectures. Finally, we evaluate the zero-shot generalization capabilities of the segmentation models on human ultrasound spinal cord images to determine whether training on our porcine dataset is sufficient for accurately interpreting human data. Our results show that the YOLOv8 detection model outperforms all evaluated models for injury localization, achieving a mean Average Precision (mAP50-95) score of 0.606. Segmentation metrics indicate that the DeepLabv3 segmentation model achieves the highest accuracy on unseen porcine anatomy, with a Mean Dice score of 0.587, while SAMed achieves the highest mean Dice score generalizing to human anatomy (0.445). To the best of our knowledge, this is the largest annotated dataset of spinal cord ultrasound images made publicly available to researchers and medical professionals, as well as the first public report of object detection and segmentation architectures to assess anatomical markers in the spinal cord for methodology development and clinical applications.

This erratum is to add author Nicholas J. Durr as a co-corresponding author.

Focused ultrasound (FUS) is an innovative technology that delivers angled acoustic energy to a small target region. Previous FUS technology has demonstrated efficacy in applications such as tumor destruction, nerve modulation, and drug delivery in the brain. We investigated the effects of low-intensity FUS (LIFU) stimulation on the spinal cord and its ability to regulate mean arterial pressure (MAP). We found that LIFU stimulation on exposed rat spinal cord could modulate MAP, causing a decrease when applied at a lower thoracic level and an increase when applied at a lumbosacral level. We also found that shorter stimulation periods (30 s) were more effective in inducing a decrease in MAP than more extended stimulation periods (90 s). The time required to return to baseline for MAP was shown to increase with subsequent periods of FUS stimulation. FUS could enable non-pharmacological, spatially targeted MAP control, especially for impaired patients. Future applications of FUS neuromodulation extend into solutions for clinical blood pressure disorders, such as autonomic dysreflexia or chronic hypertension.

ABSTRACT IMPACT: To track recovery and mitigate additional spinal cord injury (avoiding further paralysis), we are assessing the applicability of an implantable ultrasound device that can monitor the tissue health postoperatively. OBJECTIVES/GOALS: To date, no method has been developed that monitors spinal cord perfusion rate (mL/min/g) or pressure (mmHg) successfully after the surgery. Our goal is to design, construct, and validate (in animal models) a novel sensor that quantifies postoperative tissue perfusion in patients with SCI at the site of and downstream from the injury. METHODS/STUDY POPULATION: A sample size of 10 animals will allow us to test our hypothesis to track tissue perfusion before and after the SCI using ultrasound. After prepping and scrubbing the animal, the skin will be incised with a blade, bony structures will be removed and the spinal cord will be revealed. A 25-g weight will then be dropped from a height of 15 cm, and the animal will be observed for contraction of the lower extremities, a sign that the cord was damaged. Using Doppler ultrasound settings available on commercial transducers, we will investigate the acceptable frequency, as well as proper Doppler mode with and without contrast agents, and with and without elastography (stiffness mapping of the tissue). A range of frequencies will be tested (5 -25 MHz). RESULTS/ANTICIPATED RESULTS: It is expected that at frequencies 12 MHz and above, our radiologist collaborators would be able to easily detect the blood flow. It is also expected that the injury will have a noticeable effect on the changes of this detected blood flow. We aim to present figures demonstrating ultrasound image qualities obtained at various frequencies. We expect three such figures: one for gray scale ultrasound imaging, one for color Doppler and finally, one for spectral Doppler, which is the one mostly used to quantify blood flow. DISCUSSION/SIGNIFICANCE OF FINDINGS: To monitor recovery and mitigate secondary injury in patients with traumatic SCI, there is a need to monitor tissue perfusion intra-operatively. To address this need, we will design, construct, and validate a novel sensor that will postoperatively quantify tissue perfusion for the SCI patients at the site of the injury.

Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman’s ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra.

OBJECTIVES/GOALS: The first aim was to construct a controlled and high resolution FUS water tank characterization system with 1 micron step-sizes. The second aim was to create two unique standardized protocols for mapping the generated acoustic field from FUS transducers; protocol one maps the full 3D field while protocol two rapidly detects changes to the original plot. METHODS/STUDY POPULATION: To accomplish aim one, the focused ultrasound mapping platform was constructed with a water conditioning unit for water degassing and temperature control, a three-axis stage with 1 micron step-size capabilities, and a data plotting software. To measure the outcomes of aim one, the water temperature was monitored, and axis step sizes were measured through ten independent axis translation recordings. To accomplish aim two, FUS acquisitions were executed at different resolutions. For FUS localization at the cellular level, a 1-5 micron step size is required. Once the initial scan was performed, duplicate scans were executed to detect inherent perturbations or errors in the system. Once calculated, the best methods of detecting true changes to FUS signals are proposed. RESULTS/ANTICIPATED RESULTS: The FUS characterization system maintained water temperature and performed 1 micron step-sizes. While pre-existing platforms have demonstrated a resolution of one thousand recordings per cubic millimeter, the proposed system (time and computing power willing) can record one billion recordings per cubic millimeter. In practice, a resolution of 20 micron was sufficient for non-cellular level FUS characterizations. Successive 2D scans were reliably stacked to form a 3D rendering of the generated acoustic field with the average focal point intensity yielding a 1% coefficient of variation between identical scans. This inherent variation can be used as the threshold of significance for true change detection; to rapidly detect changes to the FUS signal, sampling can be performed at regions of high baseline values. DISCUSSION/SIGNIFICANCE: Focused ultrasound medical devices are gaining popularity for treatments including tumor ablation, neuromodulation, and drug delivery; however, the field lacks a standardized method to characterize these FUS transducers. The presented platform and protocols enable a rigorous and high quality translation through verification and validation.

OBJECTIVES/GOALS: This poster shares a case study on how a group at The Johns Hopkins University formed a translational lab missioned to reinvent currently existing treatments for acute spinal cord injuries, implanting in humans within a five-year window. The poster showcases how a project funded by the Defense Advanced Research Projects Agency has been implemented. METHODS/STUDY POPULATION: The translational team; Holistic Electrical; ultrasonic and Physiological Interventions Unburdening those with Spinal cord injury• (HEPIUS) Lab is composed of many parts as listed below: neurosurgeons; engineers; radiologists; public health specialists; statisticians; patient advocates; ethicists; sonographers; researchers; academic collaborators; and specialized industry partners. Sometimes physically separated; the team has videoconferencing carts across locations to stay connected at every step in the process. The lab facilities were organized with several key facets in mind: research and development (R&D); prototyping; fabrication; verification; and validation (V&V); animal model testing; cadaveric testing accessibility; mock operating room for simulations; and collaboration hubs. RESULTS/ANTICIPATED RESULTS: Due to communications with the US Food and Drug Administration (FDA), DARPA, patient advocates, ethicists, internal review boards, and other bodies, the team has a clear path towards clinical translation. The team has the following stages in progress or scheduled: manufacturing devices, benchtop testing, rat and pig models, biocompatibility testing, cadaveric testing, and clinical use. The lab space was designed to achieve these core functions. For rapid, in-house manufacturing, the lab has unique capabilities including 3D metal printing. For experiments, industry collaborations and equipment acquisitions enable the highest quality research. These technologies are assembled into diagnostic, therapeutic, testing, and manufacturing hubs to drive real change in the lives of many; the patient comes first. DISCUSSION/SIGNIFICANCE: This laboratory, team, and system of operation is aimed to enable novel practices for the clinical translation of spinal cord medical solutions. For researchers interested in launching their own translational work, this poster may serve as a reference, example, and inspiration for similar hopeful university-centered hubs.

OBJECTIVES/GOALS: The goal of our multi-institutional team is in our name Holistic Electrical, ultrasonic and Physiological Interventions Unburdening those with Spinal cord injury†(HEPIUS) Lab. Officially, I am a Ph.D. researcher, but the team has empowered me to share insights from being a former spinal cord patient myself – creating a more direct feedback loop. METHODS/STUDY POPULATION: Human-centered design is a method growing in popularity due to its impact on outcomes. Any translational project aspires to utilize some level of patient perspective. Our team has taken several initiatives to make this a part of our core. The team has a dedicated advisor who suffered a spinal cord injury and underwent the current standard of care. There are also non-traditional and unofficial advocates (like myself) on the team. Although I am fully recovered today without any symptoms from a different spinal cord complication, the team equips me with the time and support needed to share my experiences in clinic. The team gives me the opportunity to champion for the most appropriate approaches during official meetings and periodically in the lab whenever a question arises. RESULTS/ANTICIPATED RESULTS: In this poster we aim to discuss the following points: 1.) Team Culture: Those with patient insights will only share if there is an established healthy culture. 2.) Privacy: Just because someone advocates on the behalf of patients does not mean that they need to divulge personal information 3.) Workflow Structure: Sharing patient insight only reaches as far as the organization permits. Thankfully, my team is open to member perspectives and has benefited from several insights already 4.) The art of listening: Patient insights should be listened to and treated with respect, but not as an undebatable suggestion 5.) Rewarding aspects: Sharing patient insights is a very rewarding experience if you feel comfortable enough to share. DISCUSSION/SIGNIFICANCE: Translational teams often rely on statistics, one-time patient interviews, or dedicated individuals in an advocacy role to help guide the project. This poster is intended to highlight some new ways to practice engagement of patient perspectives, while introducing the intricacies of fostering healthy cultures which promote these voices.

Background Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV. Methods Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length. Results Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation ( R 2  = 0.984) and cadaveric ( R 2  = 0.951) models. The SWV decreases in all neurosurgical procedures ( p  < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords. Conclusions This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords. Plain language summary Tethered spinal cord syndrome occurs when surrounding tissue attaches to and causes stretching across the spinal cord. People with a tethered cord can experience weakness, pain, and loss of bladder control. Although increased tension in the spinal cord is known to cause these symptoms, evaluating the amount of stretching remains challenging. We investigated the ability of an ultrasound imaging approach to measure spinal cord tension. We studied our method in a computer simulation, a benchtop validation model, and in six people with tethered cords during surgery that they were undergoing to reduce tension. In each phase, the approach could detect differences between stretched spinal cords and spinal cords in a healthy state. Our method could potentially be used in the future to improve the care of people with a tethered cord. Kerensky et al. quantify tension across human spinal cords in computational simulations, a cadaveric benchtop model, and a neurosurgical case series. Their direct methodology successfully differentiates stretched spinal cords from healthy states in all sub-studies.