Deep Learning Applications for Acute Stroke Management.

Brain imaging is essential to the clinical care of patients with stroke, a leading cause of disability and death worldwide. Whereas advanced neuroimaging techniques offer opportunities for aiding acute stroke management, several factors, including time delays, inter-clinician variability, and lack of systemic conglomeration of clinical information, hinder their maximal utility. Recent advances in deep machine learning (DL) offer new strategies for harnessing computational medical image analysis to inform decision making in acute stroke. We examine the current state of the field for DL models in stroke triage. First, we provide a brief, clinical practice-focused primer on DL. Next, we examine real-world examples of DL applications in pixel-wise labeling, volumetric lesion segmentation, stroke detection, and prediction of tissue fate postintervention. We evaluate recent deployments of deep neural networks and their ability to automatically select relevant clinical features for acute decision making, reduce inter-rater variability, and boost reliability in rapid neuroimaging assessments, and integrate neuroimaging with electronic medical record (EMR) data in order to support clinicians in routine and triage stroke management. Ultimately, we aim to provide a framework for critically evaluating existing automated approaches, thus equipping clinicians with the ability to understand and potentially apply DL approaches in order to address challenges in clinical practice. ANN NEUROL 2022;92:574-587.

Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film.

PURPOSE: Transcutaneous oxygen tension (TcpO2 ) provides information about blood perfusion in the tissue immediately below the skin. These data are valuable in assessing wound healing problems, diagnosing peripheral vascular/arterial insufficiency, and predicting disease progression or the response to therapy. Currently, TcpO2 is primarily measured using electrochemical skin sensors, which consume oxygen and are prone to calibration errors. The goal of the present study was to develop a reliable method for TcpO2 measurement in human subjects. METHODS: We have developed a novel TcpO2 oximetry method based on electron paramagnetic resonance (EPR) principles with an oxygen-sensing skin adhesive film, named the superficial perfusion oxygen tension (SPOT) chip. The SPOT chip is a 3-mm diameter, 60-µm thick circular film composed of a stable paramagnetic oxygen sensor. The chip is covered with an oxygen-barrier material on one side and secured on the skin by a medical adhesive transfer tape to ensure that only the oxygen that diffuses through the skin surface is measured. The method quantifies TcpO2 through the linewidth of the EPR spectrum. RESULTS: Repeated measurements using a cohort of 10 healthy human subjects showed that the TcpO2 measurements were robust, reliable, and reproducible. The TcpO2 values ranged from 7.8 ± 0.8 to 22.0 ± 1.0 mmHg in the volar forearm skin (N = 29) and 8.1 ± 0.3 to 23.4 ± 1.3 mmHg in the foot (N = 86). CONCLUSIONS: The results demonstrated that the SPOT chip can measure TcpO2 reliably and repeatedly under ambient conditions. The SPOT chip method could potentially be used to monitor TcpO2 in the clinic.

Odontoid fractures in the pediatric population: a systematic review and management algorithm.

Purpose: The management of odontoid fractures in adult patients has been widely described. However, there is sparse literature about this injury in the pediatric population. This study aimed to review published literature regarding the management and outcomes of pediatric odontoid fractures to develop a stepwise treatment algorithm. Methods: A literature review was conducted using PRISMA guidelines on PubMed to identify studies between 1960 and 2023 that reported on the management and outcomes of odontoid fracture in pediatric patients. Studies were included if they were published in English and if their sample included at least four patients aged 0-18, minimum follow-up of 6 weeks, and outcomes for each patient clearly differentiated. Results: In total, 15 studies including 125 pediatric patients with odontoid fractures were included. Treatment options varied from non-operative management with immobilization in rigid collars, halo vests, cervicothoracic orthosis, or soft collars to surgical management with fixation and/or arthrodesis. There were 73 patients initially treated nonoperatively, 47 initially treated surgically, 2 who healed with observation alone, and 3 who died acutely of concomitant injuries. The nonunion rate for nonoperative management was 5.5%. Surgery was successful, demonstrating bony union at final follow-up, in 94.6% of cases treated via a posterior approach and 85.7% of cases treated with an anterior approach. Conclusions: Odontoid fractures must be considered in pediatric patients with cervical spine trauma. This is the largest literature review of pediatric odontoid fractures. Various management strategies exist and can be considered. The proposed algorithm offers an evidence-based framework for the management of pediatric odontoid fractures.

Outcomes of Reverse Total Shoulder Arthroplasty for Proximal Humerus Fracture Versus Rotator Cuff Arthropathy.

INTRODUCTION: Reverse total shoulder arthroplasty (RSA) is used to treat a variety of shoulder-related pathologies. This study compared medium-term clinical outcomes of less than 10-year follow-up in patients treated with RSA for proximal humerus fracture (PHF) versus rotator cuff arthropathy (RCA). METHODS: This retrospective review was conducted at two tertiary care centers, in which self-reported clinical outcomes were assessed using four validated instruments, that is, American Shoulder and Elbow Society (ASES) score, Shoulder Pain and Disability Index (SPADI), visual analog scale (VAS), and shoulder subjective value (SSV). Statistical analyses were performed using linear or logistic regression with generalized estimating equations. RESULTS: Of the 189 patients included in this study, 70 were treated for fracture and 119 for RCA. At a mean postoperative follow-up of 6.4 years, the means were 79.7 for ASES score, 20.8 for SPADI-Total, 0.8 for VAS, and 77.1 for SSV. After adjusting models for covariates, there was no significant difference in average SSV (P = 0.7), VAS (P = 0.7) or SPADI-Pain (P = 0.2) between PHF and RCA cohorts; however, the RCA cohort reported significantly better outcomes in ASES scores (P = 0.002), SPADI-Disability (P < 0.0001), and SPADI-Total (P = 0.0001). DISCUSSION: Patients with RCA and PHF treated with RSA achieved similar medium-term outcomes in several domains, particularly postoperative pain levels; however, patients with PHF reported greater perceived disability. RSA is an effective pain-controlling procedure, but patients may have variable functional outcomes based on the indication for surgery.

Bedside monitoring of hypoxic ischemic brain injury using low-field, portable brain magnetic resonance imaging after cardiac arrest.

BACKGROUND: Assessment of brain injury severity is critically important after survival from cardiac arrest (CA). Recent advances in low-field MRI technology have permitted the acquisition of clinically useful bedside brain imaging. Our objective was to deploy a novel approach for evaluating brain injury after CA in critically ill patients at high risk for adverse neurological outcome. METHODS: This retrospective, single center study involved review of all consecutive portable MRIs performed as part of clinical care for CA patients between September 2020 and January 2022. Portable MR images were retrospectively reviewed by a blinded board-certified neuroradiologist (S.P.). Fluid-inversion recovery (FLAIR) signal intensities were measured in select regions of interest. RESULTS: We performed 22 low-field MRI examinations in 19 patients resuscitated from CA (68.4% male, mean [standard deviation] age, 51.8 [13.1] years). Twelve patients (63.2%) had findings consistent with HIBI on conventional neuroimaging radiology report. Low-field MRI detected findings consistent with HIBI in all of these patients. Low-field MRI was acquired at a median (interquartile range) of 78 (40-136) hours post-arrest. Quantitatively, we measured FLAIR signal intensity in three regions of interest, which were higher amongst patients with confirmed HIBI. Low-field MRI was completed in all patients without disruption of intensive care unit equipment monitoring and no safety events occurred. CONCLUSION: In a critically ill CA population in whom MR imaging is often not feasible, low-field MRI can be deployed at the bedside to identify HIBI. Low-field MRI provides an opportunity to evaluate the time-dependent nature of MRI findings in CA survivors.

Bedside detection of intracranial midline shift using portable magnetic resonance imaging.

Neuroimaging is crucial for assessing mass effect in brain-injured patients. Transport to an imaging suite, however, is challenging for critically ill patients. We evaluated the use of a low magnetic field, portable MRI (pMRI) for assessing midline shift (MLS). In this observational study, 0.064 T pMRI exams were performed on stroke patients admitted to the neuroscience intensive care unit at Yale New Haven Hospital. Dichotomous (present or absent) and continuous MLS measurements were obtained on pMRI exams and locally available and accessible standard-of-care imaging exams (CT or MRI). We evaluated the agreement between pMRI and standard-of-care measurements. Additionally, we assessed the relationship between pMRI-based MLS and functional outcome (modified Rankin Scale). A total of 102 patients were included in the final study (48 ischemic stroke; 54 intracranial hemorrhage). There was significant concordance between pMRI and standard-of-care measurements (dichotomous, κ = 0.87; continuous, ICC = 0.94). Low-field pMRI identified MLS with a sensitivity of 0.93 and specificity of 0.96. Moreover, pMRI MLS assessments predicted poor clinical outcome at discharge (dichotomous: adjusted OR 7.98, 95% CI 2.07-40.04, p = 0.005; continuous: adjusted OR 1.59, 95% CI 1.11-2.49, p = 0.021). Low-field pMRI may serve as a valuable bedside tool for detecting mass effect.

Portable, low-field magnetic resonance imaging enables highly accessible and dynamic bedside evaluation of ischemic stroke.

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.

Use of Portable Imaging Modalities in Patients With Neurologic Disorders: A Case-Based Discussion.

Imaging technologies have significantly improved over the past few decades and play a critical role in the diagnosis and management of patients with neurologic conditions. With the evolution of these technologies to portable versions, significant implications exist for current neurologic care as well as potential improvements for the future. This article serves to describe portable imaging technologies and their potential impact on the field of neurology highlighted through the case of a patient who presented with symptoms consistent with a stroke.

Homoplasy in the evolution of modern human-like joint proportions in Australopithecus afarensis.

The evolution of bipedalism and reduced reliance on arboreality in hominins resulted in larger lower limb joints relative to the joints of the upper limb. The pattern and timing of this transition, however, remains unresolved. Here, we find the limb joint proportions of Australopithecus afarensis, Homo erectus, and Homo naledi to resemble those of modern humans, whereas those of A. africanus, Australopithecus sediba, Paranthropus robustus, Paranthropus boisei, Homo habilis, and Homo floresiensis are more ape-like. The homology of limb joint proportions in A. afarensis and modern humans can only be explained by a series of evolutionary reversals irrespective of differing phylogenetic hypotheses. Thus, the independent evolution of modern human-like limb joint proportions in A. afarensis is a more parsimonious explanation. Overall, these results support an emerging perspective in hominin paleobiology that A. afarensis was the most terrestrially adapted australopith despite the importance of arboreality throughout much of early hominin evolution.

Methodology for Low-Field, Portable Magnetic Resonance Neuroimaging at the Bedside.

Neuroimaging is a critical component of triage and treatment for patients who present with neuropathology. Magnetic resonance imaging and non-contrast computed tomography are the gold standard for diagnosis and prognostication of patients with acute brain injuries. However, these modalities require intra-hospital transport to strict, access-controlled environments, which puts critically ill patients at risk for complications and secondary injuries. A novel, portable MRI (pMRI) device that can be deployed at the patient's bedside provides a needed solution. In a dual-center investigation, Yale New Haven Hospital has obtained regular neuroimaging on patients using the pMRI as part of routine clinical care in the Emergency Department and Intensive Care Unit (ICU) since August of 2020. Massachusetts General Hospital has begun using pMRI in the Neuroscience Intensive Care Unit since January 2021. This technology has expanded the population of patients who can receive MRI imaging by increasing accessibility and timeliness for scan completion by eliminating the need for transport and increasing the potential for serial monitoring. Here we describe our methods for screening, coordinating, and executing pMRI exams and provide further detail on how to scan specific patient populations.

Portable, bedside, low-field magnetic resonance imaging for evaluation of intracerebral hemorrhage.

Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5-3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68-0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90-0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings.

Antiproliferative Effect of a Novel 4,4'-Disulfonyldiarylidenyl Piperidone in Human Colon Cancer Cells.

The synthesis and antiproliferative effect of a novel curcumin analog, 4,4'-disulfonyldiarylidenyl piperidone, are reported. The design of the molecule is based on the fusion of an antiproliferative segment, namely diarylidenyl piperidone (DAP), with N-hyroxypyrroline, which is known to metabolically convert to nitroxide and protect healthy cells. Cellular uptake, metabolic conversion, cytotoxicity and antiproliferative effect of the DAP derivative against HCT-116 human colon cancer cells have been determined. Based on cell viability and proliferation assays as well as western-blot analysis of major transcription factors and inhibitory proteins, it is determined that the DAP compound is cytotoxic by inhibiting cell survival and proliferation pathways. The findings may have important implications in the design and development of effective anticancer agents.

Supplemental Oxygen Protects Heart Against Acute Myocardial Infarction.

Myocardial infarction (MI), which occurs often due to acute ischemia followed by reflow, is associated with irreversible loss (death) of cardiomyocytes. If left untreated, MI will lead to progressive loss of viable cardiomyocytes, deterioration of cardiac function, and congestive heart failure. While supplemental oxygen therapy has long been in practice to treat acute MI, there has not been a clear scientific basis for the observed beneficial effects. Further, there is no rationale for the amount or duration of administration of supplemental oxygenation for effective therapy. The goal of the present study was to determine an optimum oxygenation protocol that can be clinically applicable for treating acute MI. Using EPR oximetry, we studied the effect of exposure to supplemental oxygen cycling (OxCy) administered by inhalation of 21-100% oxygen for brief periods (15-90 min), daily for 5 days, using a rat model of acute MI. Myocardial oxygen tension (pO2), cardiac function and pro-survival/apoptotic signaling molecules were used as markers of treatment outcome. OxCy resulted in a significant reduction of infarct size and improvement of cardiac function. An optimal condition of 30-min OxCy with 95% oxygen + 5% CO2 under normobaric conditions was found to be effective for cardioprotection.