Optimization and validation of a fat-on-a-chip model for non-invasive therapeutic drug discovery.

Obesity is a significant public health concern that is closely associated with various comorbidities such as heart disease, stroke, type II diabetes (T2D), and certain cancers. Due to the central role of adipose tissue in many disease etiologies and the pervasive nature in the body, engineered adipose tissue models are essential for drug discovery and studying disease progression. This study validates a fat-on-a-chip (FOAC) model derived from primary mature adipocytes. Our FOAC model uses a Micronit perfusion device and introduces a novel approach for collecting continuous data by using two non-invasive readout techniques, resazurin and glucose uptake. The Micronit platform proved to be a reproducible model that can effectively maintain adipocyte viability, metabolic activity, and basic functionality, and is capable of mimicking physiologically relevant responses such as adipocyte hypertrophy and insulin-mediated glucose uptake. Importantly, we demonstrate that adipocyte size is highly dependent on extracellular matrix properties, as adipocytes derived from different patients with variable starting lipid areas equilibrate to the same size in the hyaluronic acid hydrogel. This model can be used to study T2D and monitor adipocyte responses to insulin for longitudinally tracking therapeutic efficacy of novel drugs or drug combinations.

Increasing Risks to the Health of the Invertebrates-Balancing between Harm and Benefit.

The article discusses the issue of extensive use of detergents and sanitizers in the time of new challenges associated with the COVID-19 (SARS-CoV-2) pandemic. These agents could pose threats to the existence of free-living invertebrates as essential components of the ecosystem. The biological effects of the mentioned classes of substances, their metabolites, and combined effects in the mixture have not been studied enough. The main challenges in trying to balance the threats and benefits of using such substances are the lack of knowledge of the biological effects of these products, the gaps in testing invertebrates' responses, and changes in environment-related regulations to minimize risks to animals and humans. Numerous studies in this field still leave research gaps, particularly concerning the combined toxicity of well-known and widely used disinfectants, surfactants, and heavy metals, posing potential future challenges. Additionally, the review identified the need for additional testing of invertebrates for their sensitivity to disinfectants and surfactants of different compositions, including improved (non-invasive) methods, studies for early life stages, and comparative studies of species resilience.

Assessing the feasibility of digital keypress statistics to detect seizures and capture cognitive impairment in patients with epilepsy: A pilot study.

BACKGROUND: Efficient, non-invasive monitoring may provide a more accurate and comprehensive understanding of seizure frequency and the development of some comorbidities in people with epilepsy. Novel keyboard technology measuring digital keypress statistics has demonstrated its practical value for neurodegenerative diseases including Parkinson's Disease and Dementia. Smartphones integrated into daily life may serve as a low-burden longitudinal monitoring system for patients with epilepsy. OBJECTIVE: This study aimed to assess the feasibility of keyboard statistics as an objective measure of seizure frequency for patients with epilepsy, in addition to tracking differences between cognitively normal and cognitively impaired patients. METHODS: Six adult patients admitted to the Epilepsy Monitoring Unit (EMU) at Mayo Clinic in Rochester, Minnesota were studied. The keyboard was installed on the patient's smartphone. In the EMU, typing statistics were correlated to electroencephalogram (EEG) confirmed seizures. After discharge, participants continued using their keyboards and kept a seizure log. We also analyzed the key press/release times and usage of participants' keyboards for adherence. RESULTS: Keyboard sessions during and after seizures assessed for key press/release differences versus baseline showed no statistically significant difference (p = 0.44). Using one-way ANOVA, cognitive impairment's potential impact on keyboard statistics was explored in patients who had neuropsychological testing (N = 3). Significant differences were found between patients with and without cognitive impairment (p < 0.001). No significant difference was noted between patients with mild intellectual disability and normal cognitive function (p = 0.55).

Non-invasive prediction of massive transfusion during surgery using intraoperative hemodynamic monitoring data.

OBJECTIVE: Failure to receive prompt blood transfusion leads to severe complications if massive bleeding occurs during surgery. For the timely preparation of blood products, predicting the possibility of massive transfusion (MT) is essential to decrease morbidity and mortality. This study aimed to develop a model for predicting MT 10 min in advance using non-invasive bio-signal waveforms that change in real-time. METHODS: In this retrospective study, we developed a deep learning-based algorithm (DLA) to predict intraoperative MT within 10 min. MT was defined as the transfusion of 3 or more units of red blood cells within an hour. The datasets consisted of 18,135 patients who underwent surgery at Seoul National University Hospital (SNUH) for model development and internal validation and 621 patients who underwent surgery at the Boramae Medical Center (BMC) for external validation. We constructed the DLA by using features extracted from plethysmography (collected at 500 Hz) and hematocrit measured during surgery. RESULTS: Among 18,135 patients in SNUH and 621 patients in BMC, 265 patients (1.46%) and 14 patients (2.25%) received MT during surgery, respectively. The area under the receiver operating characteristic curve (AUROC) of DLA predicting intraoperative MT before 10 min was 0.962 (95% confidence interval [CI], 0.948-0.974) in internal validation and 0.922 (95% CI, 0.882-0.959) in external validation, respectively. CONCLUSION: The DLA can successfully predict intraoperative MT using non-invasive bio-signal waveforms.

Integrating microneedles and sensing strategies for diagnostic and monitoring applications: The state of the art.

Microneedles (MNs) offer minimally-invasive access to interstitial fluid (ISF) - a potent alternative to blood in terms of monitoring physiological analytes. This property is particularly advantageous for the painless detection and monitoring of drugs and biomolecules. However, the complexity of the skin environment, coupled with the inherent nature of the analytes being detected and the inherent physical properties of MNs, pose challenges when conducting physiological monitoring using this fluid. In this review, we discuss different sensing mechanisms and highlight advancements in monitoring different targets, with a particular focus on drug monitoring. We further list the current challenges facing the field and conclude by discussing aspects of MN design which serve to enhance their performance when monitoring different classes of analytes.

Sensor-integrated brain-on-a-chip platforms: Improving the predictive validity in neurodegenerative research.

Affecting millions of individuals worldwide, neurodegenerative diseases (NDDs) pose a significant and growing health concern in people over the age of 60 years. Contributing to this trend are the steady increase in the aging population coupled with a persistent lack of disease-altering treatment strategies targeting NDDs. The absence of efficient therapeutics can be attributed to high failure rates in clinical trials and the ineptness of animal models in preceding preclinical studies. To that end, in recent years, significant research effort has been dedicated to the development of human cell-based preclinical disease models characterized by a higher degree of predictive validity. However, a key requirement of any in vitro model constitutes the precise knowledge and replication of the target tissues' (patho-)physiological microenvironment. Herein, microphysiological systems have demonstrated superiority over conventional static 2D/3D in vitro cell culture systems, as they allow for the emulation and continuous monitoring of the onset, progression, and remission of disease-associated phenotypes. This review provides an overview of recent advances in the field of NDD research using organ-on-a-chip platforms. Specific focus is directed toward non-invasive sensing strategies encompassing electrical, electrochemical, and optical sensors. Additionally, promising on- and integrable off-chip sensing strategies targeting key analytes in NDDs will be presented and discussed in detail.

Recent Technologies for Transcutaneous Oxygen and Carbon Dioxide Monitoring.

The measurement of partial pressures of oxygen (O2) and carbon dioxide (CO2) is fundamental for evaluating a patient's conditions in clinical practice. There are many ways to retrieve O2/CO2 partial pressures and concentrations. Arterial blood gas (ABG) analysis is the gold standard technique for such a purpose, but it is invasive, intermittent, and potentially painful. Among all the alternative methods for gas monitoring, non-invasive transcutaneous O2 and CO2 monitoring has been emerging since the 1970s, being able to overcome the main drawbacks of ABG analysis. Clark and Severinghaus electrodes enabled the breakthrough for transcutaneous O2 and CO2 monitoring, respectively, and in the last twenty years, many innovations have been introduced as alternatives to overcome their limitations. This review reports the most recent solutions for transcutaneous O2 and CO2 monitoring, with a particular consideration for wearable measurement systems. Luminescence-based electronic paramagnetic resonance and photoacoustic sensors are investigated. Optical sensors appear to be the most promising, giving fast and accurate measurements without the need for frequent calibrations and being suitable for integration into wearable measurement systems.

Accuracy of Transcutaneous Carbon Dioxide Measurement During Transcatheter Aortic Valve Replacement Under Monitored Anesthesia Care: A Prospective Observational Study.

Background Transcutaneous carbon dioxide tension (PtcCO2) measurement is a promising alternative to arterial carbon dioxide tension (PaCO2) measurement. PaCO2 measurement is invasive and intermittent, whereas PtcCO2 measurement is non-invasive and continuous. However, previous studies evaluating PtcCO2measurements did not include patients undergoing transcatheter aortic valve replacement (TAVR), who experience anticipated hemodynamic changes, particularly before and after valve placement. Therefore, we investigated whether PtcCO2 measurement could provide an alternative to PaCO2 measurement during transfemoral TAVR under monitored anesthesia care (MAC) with local anesthesia. Methodology We conducted a prospective observational study. We included all consecutive patients with severe aortic stenosis who were scheduled to undergo a transfemoral TAVR under MAC at our institution from November 1, 2020, to April 30, 2021. During the procedures, PaCO2 and PtcCO2 were concurrently monitored six times as a reference standard and index test, respectively. PtcCO2 was monitored continuously using a non-invasive earlobe sensor. The agreement between PtcCO2 and PaCO2 measurements was assessed using the Bland-Altman method, and the 95% limits of agreement were calculated. Based on previous studies, we determined that 95% limits of agreement of ±6.0 mmHg would be clinically acceptable to define PtcCO2 as an alternative to PaCO2. Results We obtained 88 measurement pairs from 15 patients. The lower and upper 95% limits of agreement between the PtcCO2 and PaCO2 measurements were -4.22 mmHg and 6.56 mmHg, respectively. Conclusions During TAVR under MAC with local anesthesia, PtcCO2 measurement could not provide a viable alternative to PaCO2 measurement to reduce high PaCO2 events. This study focused on comparing intraoperative periods before and after valve implantation. Therefore, further investigation is warranted to assess the impact of various factors, including the prosthetic valve type and the hemodynamic effects of balloon aortic valvuloplasty, on PtcCO2 measurement in TAVR.

UCNPs-labeled electrospun scaffolds used to monitor in vivo degradation and bone tissue regeneration.

Biodegradable electrospun bone repair materials are effective means to treat bone defects. However, because the electrospun substrates are mostly organic polymer materials, there is a lack of real-time and intuitive monitoring methods for their degradation in vivo. Therefore, it is of great significance to develop in vivo traced electrospun bone repair materials for postoperative observation of their degradation. In this research, polycaprolactone/up-conversion nanoparticles/magnesium oxide (PCL/UCNPs/MgO) composite scaffolds were prepared by electrospun based on the luminescence characteristics of up-conversion nanoparticles (UCNPs) under near infrared excitation and the osteogenic ability of MgO. The in vivo and in vitro degradation results showed that with the increase of time, the electrospun scaffolds gradually degraded and its luminescence intensity decreased. The addition of UCNPs can effectively monitor the degradation of the scaffolds. In addition, the prepared electrospun scaffolds had great biocompatibility, among which PCL-1%UCNPs-1%MgO (P1U1M) electrospun scaffolds had obvious effect on promoting osteogenic differentiation of mouse embryonic osteoblasts cells (MC3T3-E1) in vitro. In conclusion, P1U1M electrospun scaffolds have the potential to induce bone regeneration at bone defect sites, and can monitor the degradation of electrospun scaffolds. It may be a potential candidate material for bone regeneration in defect area.

Corrigendum: Determination of aortic characteristic impedance and total arterial compliance from regional pulse wave velocities using machine learning: an in silico study.

[This corrects the article DOI: 10.3389/fbioe.2021.649866.].

The evaluation of a non-invasive respiratory monitor in ards patients in supine and prone position.

PURPOSE: The Prone positioning in addition to non invasive respiratory support is commonly used in patients with acute respiratory failure. The aim of this study was to assess the accuracy of an impedance-based non-invasive respiratory volume monitor (RVM) in supine and in prone position. METHODS: In sedated, paralyzed and mechanically ventilated patients in volume-controlled mode with acute respiratory distress syndrome scheduled for prone positioning it was measured and compared non-invasively tidal volume and respiratory rate provided by the RVM in supine and, subsequently, in prone position, by maintaining unchanged the ventilatory setting. RESULTS: Forty patients were enrolled. No significant difference was found between measurements in supine and in prone position either for tidal volume (p = 0.795; p = 0.302) nor for respiratory rate (p = 0.181; p = 0.604). Comparing supine vs. prone position, the bias and limits of agreements for respiratory rate were 0.12 bpm (-1.4 to 1.6) and 20 mL (-80 to 120) for tidal volume. CONCLUSIONS: The RVM is accurate in assessing tidal volume and respiratory rate in prone compared to supine position. Therefore, the RVM could be applied in non-intubated patients with acute respiratory failure receiving prone positioning to monitor respiratory function.

A pilot clinical study to estimate intracranial pressure utilising cerebral photoplethysmograms in traumatic brain injury patients.

PURPOSE: In this research, a non-invasive intracranial pressure (nICP) optical sensor was developed and evaluated in a clinical pilot study. The technology relied on infrared light to probe brain tissue, using photodetectors to capture backscattered light modulated by vascular pulsations within the brain's vascular tissue. The underlying hypothesis was that changes in extramural arterial pressure could affect the morphology of recorded optical signals (photoplethysmograms, or PPGs), and analysing these signals with a custom algorithm could enable the non-invasive calculation of intracranial pressure (nICP). METHODS: This pilot study was the first to evaluate the nICP probe alongside invasive ICP monitoring as a gold standard. nICP monitoring occurred in 40 patients undergoing invasive ICP monitoring, with data randomly split for machine learning. Quality PPG signals were extracted and analysed for time-based features. The study employed Bland-Altman analysis and ROC curve calculations to assess nICP accuracy compared to invasive ICP data. RESULTS: Successful acquisition of cerebral PPG signals from traumatic brain injury (TBI) patients allowed for the development of a bagging tree model to estimate nICP non-invasively. The nICP estimation exhibited 95% limits of agreement of 3.8 mmHg with minimal bias and a correlation of 0.8254 with invasive ICP monitoring. ROC curve analysis showed strong diagnostic capability with 80% sensitivity and 89% specificity. CONCLUSION: The clinical evaluation of this innovative optical nICP sensor revealed its ability to estimate ICP non-invasively with acceptable and clinically useful accuracy. This breakthrough opens the door to further technological refinement and larger-scale clinical studies in the future. TRIAL REGISTRATION: NCT05632302, 11th November 2022, retrospectively registered.

Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value.

Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-ß-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL (n = 14) and controls undergoing elective termination of pregnancy (n = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free ß-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free ß-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-ß-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.

Ultra-conformal epidermal antenna for multifunctional motion artifact-free sensing and point-of-care monitoring.

Accurate acquisition of physiological and physical information from human tissue is essential for health monitoring, disease prevention and treatment. The existing antennas with traditional rigid or flexible substrates are susceptible to motion artifacts in wearable applications due to the miniaturization limitation and lack of proper adhesion and conformal interfaces with the skin. Recent advances in wearable radio frequency (RF) bioelectronics directly drawn on the skin are a promising solution for future skin-interfaced devices. Herein, we present a first-of-its kind epidermal antenna architecture with skin as the antenna substrate, which is ultra-low profile, ultra-conformal, ultra-compact, and simple fabrication without specialized equipment. The radiation unit and ground of antenna are drawn directly on the skin with the strong adhesion and ultra conformality. Therefore, this RF device is highly adaptable to motion. As a proof-of- feasibility, epidermal antenna can be freely drawn on demand at different locations on the skin for the development of temperature sensor, skin hydration sensor, strain sensor, glucose sensor and other devices. An epidermal antenna-based temperature sensor can offer accurate and real-time monitoring of human body temperature changes in the ultra-wideband (UWB) range. The results during the monitoring of hydration level with and without stretching show that the epidermal antenna drawn on the skin is motion artifact-free. We also designed an epidermal antenna array employing a horseshoe-shaped configuration for the precise identification of various gestures. In addition, the non-invasive blood glucose level (BGL) monitoring results during the in-vivo experiments report high correlation between the epidermal antenna responses and BGLs, without any time hysteresis. After the prediction of BGL by BP network, all the predicted BGL values are fallen 100% into the clinically acceptable zones. Together, these results show that epidermal antenna offers a promising new approach for biosensing platform.

A non-invasive continuous and real-time volumetric monitoring in spontaneous breathing subjects based on bioimpedance-ExSpiron®Xi: a validation study in healthy volunteers.

Tidal volume (TV) monitoring breath-by-breath is not available at bedside in non-intubated patients. However, TV monitoring may be useful to evaluate the work of breathing. A non-invasive device based on bioimpedance provides continuous and real-time volumetric tidal estimation during spontaneous breathing. We performed a prospective study in healthy volunteers aimed at evaluating the accuracy, the precision and the trending ability of measurements of ExSpiron®Xi as compared with the gold standard (i.e. spirometry). Further, we explored whether the differences between the 2 devices would be improved by the calibration of ExSpiron®Xi with a pre-determined tidal volume. Analysis accounted for the repeated nature of measurements within each subject. We enrolled 13 healthy volunteers, including 5 men and 8 women. Tidal volume, TV/ideal body weight (IBW) and respiratory rate (RR) measured with spirometer (TVSpirometer) and with ExSpiron®Xi (TVExSpiron) showed a robust correlation, while minute ventilation (MV) showed a weak correlation, in both non/calibrated and calibrated steps. The analysis of the agreement showed that non-calibrated TVExSpiron underestimated TVspirometer, while in the calibrated steps, TVExSpiron overestimated TVspirometer. The calibration procedure did not reduce the average absolute difference (error) between TVSpirometer and TVExSpiron. This happened similarly for TV/IBW and MV, while RR showed high accuracy and precision. The trending ability was excellent for TV, TV/IBW and RR. The concordance rate (CR) was >95% in both calibrated and non-calibrated measurements. The trending ability of minute ventilation was limited. Absolute error for both calibrated and not calibrated values of TV, TV/IBW and MV accounting for repeated measurements was variably associated with BMI, height and smoking status. Conclusions: Non-invasive TV, TV/IBW and RR estimation by ExSpiron®Xi was strongly correlated with tidal ventilation according to the gold standard spirometer technique. This data was not confirmed for MV. The calibration of the device did not improve its performance. Although the accuracy of ExSpiron®Xi was mild and the precision was limited for TV, TV/IBW and MV, the trending ability of the device was strong specifically for TV, TV/IBW and RR. This makes ExSpiron®Xi a non-invasive monitoring system that may detect real-time tidal volume ventilation changes and then suggest the need to better optimize the patient ventilatory support.

The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study.

OBJECTIVES: Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. METHODS: Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. RESULTS: A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 µmol/L to 19.69 µmol/L, and saliva, from 59.00 µmol/L to 13.70 µmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). CONCLUSIONS: The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.

Capacitive spectroscopy as transduction mechanism for wearable biosensors: opportunities and challenges.

Wearable sensors would revolutionize healthcare and personalized medicine by providing individuals with continuous and real-time data about their bodies and environments. Their integration into everyday life has the potential to enhance well-being, improve healthcare outcomes, and offer new opportunities for research. Capacitive sensors technology has great potential to enrich wearable devices, extending their use to more accurate physiological indicators. On the basis of capacitive sensors developed so far to monitor physical parameters, and taking into account the advances in capacitive biosensors, this work discusses the benefits of this type of transduction to design wearables for the monitoring of biomolecules. Moreover, it provides insights into the challenges that must be overcome to take advantage of capacitive transduction in wearable sensors for health.

Integrating Fluorescence and Magnetic Resonance Imaging in Biocompatible Scaffold for Real-Time Bone Repair Monitoring and Assessment.

In situ monitoring of bone tissue regeneration progression is critical for the development of bone tissue engineering scaffold. However, engineered scaffolds that can stimulate osteogenic progress and allow for non-invasive monitoring of in vivo bone regeneration simultaneously are rarely reported. Based on a hard-and-soft integration strategy, a multifunctional scaffold composed of 3D printed microfilaments and a hydrogel network containing simvastatin (SV), indocyanine green-loaded superamphiphiles, and aminated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NH2 ) is fabricated. Both in vitro and in vivo results demonstrate that the as-prepared scaffold significantly promotes osteogenesis through controlled SV release. The biocomposite scaffold exhibits alkaline phosphatase-responsive near-infrared II fluorescence imaging. Meanwhile, USPIO-NH2 within the co-crosslinked nanocomposite network enables the visualization of scaffold degradation by magnetic resonance imaging. Therefore, the biocomposite scaffold enables or facilitates non-invasive in situ monitoring of neo-bone formation and scaffold degradation processes following osteogenic stimulation, offering a promising strategy to develop theranostic scaffolds for tissue engineering.

Non-Invasive Methods for Intracranial Pressure Monitoring in Traumatic Brain Injury Using Transcranial Doppler: A Scoping Review.

Intracranial pressure (ICP) monitoring is necessary for managing patients with traumatic brain injury (TBI). Although gold-standard methods include intraventricular or intraparenchymal transducers, these systems cannot be used in patients with coagulopathies or in those who are at high risk of catheter-related infections, nor can they be used in resource-constrained settings. Therefore, a non-invasive modality that is more widely available, cost effective, and safe would have tremendous impact. Among such non-invasive choices, transcranial Doppler (TCD) provides indirect ICP estimates through waveform analysis of cerebral hemodynamic changes. The objective of this scoping review is to describe the existing evidence for the use of TCD-derived methods in estimating ICP in adult TBI patients as compared with gold-standard invasive methods. This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and Embase. The search was limited to studies conducted in adult TBI patients published in any language between 2012 and 2022. Twenty-two studies were included for analysis, with most being prospective studies conducted in high-income countries. TCD-derived non-invasive ICP (nICP) methods are either mathematical or non-mathematical, with the former having slightly better correlation with invasive methods, especially when using time-trending ICP dynamics over one-time estimated values. Nevertheless, mathematical methods are associated with greater cost and complexity in their application. Formula-based methods showed promise in excluding elevated ICP, exhibiting a high negative predictive value. Therefore, TCD-derived methods could be useful in assessing ICP changes instead of absolute ICP values for high-risk patients, especially in low-resource settings.