Optical Biomarkers Research Articles

Multiphoton imaging-based quantifiable collagen signatures for predicting outcomes in patients with pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) presents a clinical challenge due to its poor prognosis and high mortality rate. Here, we aimed to enhance the prognostic prediction of patients with PDAC by studying collagen features in tumor microenvironment using multiphoton microscopy (MPM) combining with image processing technique. We identified eight distinct tumor-associated collagen signatures (TACS1-8) from multiphoton images of PDAC tissues and developed an optical biomarker, TACS-score, based on the TACS1-8 using ridge regression analysis. Additionally, we also extracted 142 microscopic TACS (M-TACS) from second-harmonic generation (SHG) images and constructed a new robust biomarker, M-TACS-score, using the least absolute shrinkage and selection operator (LASSO) regression analysis. Our statistical results demonstrate that as two new optical biomarkers, TACS- and M-TACS-score, are independent prognostic factors and have good discriminatory ability (high AUC) as well as risk stratification (high HR) comparing with traditional clinical model (combining seven clinical risk factors, age, sex, TNM stage, tumor location and differentiation, perineural and lymph-vascular invasion) in predicting overall survival (OS) of patients with PDAC, highlighting their potential prognostic and predictive value. A combination of label-free multiphoton imaging technique and computer-aided image processing method may offer a novel and promising approach for finding new biomarkers to improve prognosis prediction and thereby tailor treatment strategies more effectively.

Hyperspectral analysis to assess gametocytogenesis stage progression in malaria-infected human erythrocytes.

Developments of anti-gametocyte drugs have been delayed due to insufficient understanding of gametocyte biology. We report a systematic workflow of data processing algorithms to quantify changes in the absorption spectrum and cell morphology of single malaria-infected erythrocytes. These changes may serve as biomarkers instrumental for the future development of antimalarial strategies, especially for anti-gametocyte drug design and testing. Image-based biomarkers may also be useful for nondestructive, label-free malaria detection and drug efficacy evaluation in resource-limited communities. We extend the application of hyperspectral microscopy to provide detailed insights into gametocyte stage progression through the quantitative analysis of absorbance spectra and cell morphology in malaria-infected erythrocytes. Malaria-infected erythrocytes at asexual and different gametocytogenesis stages were imaged through hyperspectral confocal microscopy. The preprocessing of the hyperspectral data cubes to transform them to color images and spectral angle mapper (SAM) analysis were first used to segment hemoglobin (Hb)- and hemozoin (Hz)-abundant areas within the host erythrocytes. Correlations between changes in cell morphology and increasing Hz-abundant areas of the infected erythrocytes were then examined to test their potential as optical biomarkers to determine the progression of infection, involving transitions from asexual to various gametocytogenesis stages. Following successful segmentation of Hb- and Hz-abundant areas in malaria-infected erythrocytes through SAM analysis, a modest correlation between the segmented Hz-abundant area and cell shape changes over time was observed. A significant increase in both the areal fraction of Hz and the ellipticity of the cell confirms that the Hz fraction change correlates with the progression of gametocytogenesis. Our workflow enables the quantification of changes in host cell morphology and the relative contents of Hb and Hz at various parasite growth stages. The quantified results exhibit a trend that both the segmented areal fraction of intracellular Hz and the ellipticity of the host cell increase as gametocytogenesis progresses, suggesting that these two metrics may serve as useful biomarkers to determine the stage of gametocytogenesis.

Raman spectroscopic probe provides optical biomarkers of cartilage composition predictive of tissue function.

The diagnosis of early osteoarthritis when therapeutic interventions may be most effective at reversing cartilage degeneration presents a clinical challenge. We describe a Raman arthroscopic probe and spectral analysis that measures biomarkers reflective of the content of predominant cartilage ECM constituents-glycosaminoglycans (GAG), collagen, water-essential to cartilage function. We compare the capability of Raman-probe-derived biomarkers to predict functional properties of cartilage to quantitative MRI and histopathology assessments. Osteochondral blocks were sectioned from 6 bovine femoral condyles with no macroscopic injury (n=62 blocks) and 6 condyles with a focal chondral lesion (n=32 blocks), but no macroscopic degeneration of surrounding cartilage (n=34 blocks). Blocks from 10 human knees were further analyzed (age 27-75;n=235 blocks). Using a custom arthroscopic Raman spectroscopy probe, spectra of chondral layers were measured and subjected to multivariate linear decomposition to extract ECM biomarker scores, reflecting the contribution of each ECM constituent to the spectra. Blocks were further analyzed for elastic modulus, T2/T2* MRI relaxation times, and OARSI scores. For bovine tissues, Raman biomarkers revealed depleted GAG and cartilage softening peripheral to the lesion despite no macroscopic degeneration. Raman biomarkers accounted for 78% of GAG content variation and 71% of modulus variation. For human tissues, Raman biomarkers accounted for 71% of modulus variation. Raman biomarkers accounted for a greater variation of modulus (71%-72%) than OARSI (12-54%), T2* (15%-27%), or T2 (25%-30%). These data support the application of Raman probe-derived biomarkers for molecular assessment of key ECM constituents that define cartilage properties in health and disease.

Spectroscopic Analysis of Tryptophan as a Potential Optical Biomarker for Estimating the Time of Death.

The estimation of the time of death represents a highly complex and challenging task within the field of forensic medicine and science. It is essential to approach this matter with the utmost respect for human rights while acknowledging the inherent limitations of the current methods, which require continuous refinement and expansion. Forensic science recognizes the necessity to improve existing techniques and develop new, more accurate, and non-invasive procedures, such as physicochemical approaches, to enhance the precision and reliability of time of death determinations. This article proposes a novel, non-invasive method for estimating the time of death using a spectroscopic analysis of tryptophan. The initial phase of the study concerns the presentation of the spectroscopic properties of tryptophan at varying pH levels, with consideration given to the pH fluctuations that occur during the decomposition of cadavers. The findings confirm the stability of the spectroscopic properties at different environmental pH levels. Subsequently, preliminary trials were conducted on 15 healthy human volunteers, which demonstrated that tryptophan concentrations in fingerprint samples were within the detection limits using molecular spectroscopy techniques. The final objective was to ascertain whether the composition of the substance present on the skin surface of a deceased individual up to 48 h postmortem is comparable to that of the sweat-fatty substance in living individuals. This was confirmed by the absorption and emission spectral profiles, which showed overlapping patterns with those obtained from living volunteers. The most significant outcome at this stage was the demonstration of a considerable increase in emission intensity in the spectra for samples obtained approximately 48 h after death in comparison to that obtained from a sample taken approximately 24 h after death. This indicates a rise in the concentration of tryptophan on the skin surface as the postmortem interval (PMI) increases, which could serve as a basis for developing a tool to estimate the time of death.

An ultrathin organic–inorganic integrated device for optical biomarker monitoring

An ultrathin organic–inorganic integrated device for optical biomarker monitoring

LONG-TERM VISUAL OUTCOMES AND OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS IN EYES WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy. Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis. The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018). In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.

In vivo monitoring of active subretinal fibrosis in mice using collagen hybridizing peptides

Subretinal fibrosis is associated with worse visual outcomes in patients with neovascular age-related macular degeneration. As there is a lack of optimal biomarkers and no method that directly detects collagen in the back of the eye, novel tools that monitor fibrosis-related changes in neovascular age-related macular degeneration are needed. Here, using two mouse models (the laser-induced choroidal neovascularization model, and the JR5558 mouse presenting with spontaneous subretinal neovascularization with fibrosis), we imaged active fibrotic lesions using fluorescently labeled collagen hybridizing peptides (CHPs), short peptides that bind to single α-chain collagen structures during collagen remodeling. JR5558 retinal pigment epithelium/choroid flat mounts showed CHP co-staining with fibrosis and epithelial mesenchymal transition-related markers; additionally, CHP histopathology staining correlated with in vivo CHP imaging. After laser-induced choroidal neovascularization, in vivo CHP binding correlated with laser intensity, histopathology CHP and fibronectin staining. Laser-induced choroidal neovascularization showed decreased CHP intensity over time in healing/regressing versus active scars in vivo, whereas increased CHP binding correlated with elevated fibrosis in JR5558 mouse eyes with age. In bispecific angiopoietin 2/vascular endothelial growth factor antibody-treated JR5558 mice, CHPs detected significantly decreased collagen remodeling versus immunoglobulin G control. These results demonstrate the first use of CHPs to directly image remodeling collagen in the eye and as a potential clinical optical biomarker of active subretinal fibrosis associated with ocular neovascularization.

Non-invasive optical and laboratory hematologic biomarkers correlate in patients with sickle cell disease.

The goal of this study is to identify non-invasive optical hemodynamic biomarkers that can index laboratory hematology measurements in sickle cell disease (SCD). We acquired frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS) data from the forearms and foreheads of 17 participants in a randomized, double-blind, placebo-controlled trial evaluating effects of isoquercetin (IQ) on thromboinflammation in SCD. We observed multiple, significant correlations between optical and hematology biomarkers including cerebral tissue oxygen saturation (StO2) and hematocrit (HCT); oxyhemoglobin ([O2Hb]) recovery rate and intercellular adhesion molecule 1 (ICAM-1); and blood flow index (BFI) reperfusion rate and coagulation index (CI). The potential of these non-invasive optical biomarkers for assessing vascular pathophysiology for the management of SCD warrants further exploration.

Towards machine learning-based quantitative hyperspectral image guidance for brain tumor resection

BackgroundComplete resection of malignant gliomas is hampered by the difficulty in distinguishing tumor cells at the infiltration zone. Fluorescence guidance with 5-ALA assists in reaching this goal. Using hyperspectral imaging, previous work characterized five fluorophores’ emission spectra in most human brain tumors.MethodsIn this paper, the effectiveness of these five spectra was explored for different tumor and tissue classification tasks in 184 patients (891 hyperspectral measurements) harboring low- (n = 30) and high-grade gliomas (n = 115), non-glial primary brain tumors (n = 19), radiation necrosis (n = 2), miscellaneous (n = 10) and metastases (n = 8). Four machine-learning models were trained to classify tumor type, grade, glioma margins, and IDH mutation.ResultsUsing random forests and multilayer perceptrons, the classifiers achieve average test accuracies of 84–87%, 96.1%, 86%, and 91% respectively. All five fluorophore abundances vary between tumor margin types and tumor grades (p < 0.01). For tissue type, at least four of the five fluorophore abundances are significantly different (p < 0.01) between all classes.ConclusionsThese results demonstrate the fluorophores’ differing abundances in different tissue classes and the value of the five fluorophores as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

Prognostic significance of collagen signatures in pancreatic ductal adenocarcinoma obtained from second-harmonic generation imaging

BackgroundPancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies.MethodsHere we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures.ResultsSHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification.ConclusionsSHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions.

Label-free metabolic optical biomarkers track stem cell fate transition in real time.

Tracking stem cell fate transition is crucial for understanding their development and optimizing biomanufacturing. Destructive single-cell methods provide a pseudotemporal landscape of stem cell differentiation but cannot monitor stem cell fate in real time. We established a metabolic optical metric using label-free fluorescence lifetime imaging microscopy (FLIM), feature extraction and machine learning-assisted analysis, for real-time cell fate tracking. From a library of 205 metabolic optical biomarker (MOB) features, we identified 56 associated with hematopoietic stem cell (HSC) differentiation. These features collectively describe HSC fate transition and detect its bifurcate lineage choice. We further derived a MOB score measuring the "metabolic stemness" of single cells and distinguishing their division patterns. This score reveals a distinct role of asymmetric division in rescuing stem cells with compromised metabolic stemness and a unique mechanism of PI3K inhibition in promoting ex vivo HSC maintenance. MOB profiling is a powerful tool for tracking stem cell fate transition and improving their biomanufacturing from a single-cell perspective.

Optical biomarker analysis for renal cell carcinoma obtained from preoperative and postoperative patients using ATR-FTIR spectroscopy

Renal cell carcinoma (RCC) is the most common malignant tumor in the urinary system, accounting for 80 % to 90 % for all renal malignancies. Traditional diagnostic methods like magnetic resonance imaging (MRI) and computed tomography (CT) lack the sensitivity and specificity as they lack specific biomarkers. These limitations impede effective monitoring of tumor recurrence. This study aims to employ Attenuated Total Reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy, an optical technology sensitive to molecular groups, to analyze the potential optical biomarkers in urine and plasma samples from RCC patients pre- and post-surgery. The results reveal distinctive spectral information from both plasma and urine samples. Post-surgery urine spectra exhibit complexity compared to plasma, showing reduced content at 1072 cm−1, 1347 cm−1 and 1654 cm−1 bands, while increased content at 1112 cm−1, 1143 cm−1, 1447 cm−1, 3334 cm−1 and 3420 cm−1 bands. Utilizing machine learning models such as eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), partial least squares (PLS), and artificial neural network (ANN), the study evaluated plasma and urine samples pre- and post-surgery. Remarkably, the XGBoost method excelled in distinguishing between tumor conditions and recovery, achieving an impressive AUC value of 0.99. These results underscore the potential of ATR-FTIR technology in identifying RCC optical biomarkers, with XGBoost showing promise as a valuable screening tool for RCC recurrence diagnosis.

Synergistic Assembly of 1DZnO and Anti-CYFRA 21-1: A Physicochemical Approach to Optical Biosensing.

Objective: We conducted a comprehensive physicochemical analysis of one-dimensional ZnO nanowires (1DZnO), incorporating anti-CYFRA 21-1 immobilization to promote fast optical biomarker detection up to 10 ng ml-1. Impact Statement: This study highlights the effectiveness of proof-of-concept 1DZnO nanoplatforms for rapid cancer biomarker detection by examining the nanoscale integration of 1DZnO with these bioreceptors to deliver reliable photoluminescent output signals. Introduction: The urgent need for swift and accurate prognoses in healthcare settings drives the rise of sensitive biosensing nanoplatforms for cancer detection, which has benefited from biomarker identification. CYFRA 21-1 is a reliable target for the early prediction of cancer formation that can be perceptible in blood, saliva, and serum. However, 1DZnO nanostructures have been barely applied for CYFRA 21-1 detection. Methods: We assessed the nanoscale interaction between 1DZnO and anti-CYFRA 21-1 antibodies to develop rapid CYFRA 21-1 detection in two distinct matrices: PhosphateBuffered Saline (PBS) buffer and artificial saliva. The chemical modifications were tracked utilizing Fourier transform infrared spectroscopy, while transmission electron microscopy and energy dispersive spectroscopy confirmed antigen-antibody interplay over nanostructures. Results: Our results show high antibody immobilization efficiencies, affirming the effectiveness of 1DZnO nanoplatforms for rapid CYFRA 21-1 testing within a 5-min detection window in both PBS and artificial saliva. Photoluminescence measurements also revealed distinct optical responses across biomarker concentrations ranging from 10 to 1,000 ng ml-1. Conclusion: Discernible PL signal responses obtained after 5 min affirm the potential of 1DZnO nanoplatforms for further advancement in optical biomarker detection for application in early cancer prognosis.

INNV-24. MACHINE LEARNING-BASED SPECTROSCOPIC TISSUE DIFFERENTIATION IN FLUORESCENCE-GUIDED NEUROSURGERY

Abstract Maximal resection of malignant gliomas is hindered by difficulty in distinguishing tumor margins. Fluorescence-guided resection with 5-ALA assists in reaching this goal. Previously, we characterized five fluorophore emissions that accurately represent any spectrum measured from human brain tumor biopsies with a wide-field hyperspectral device. In this study, the effectiveness of these five spectra was explored for different tumor classification tasks in 891 hyperspectral widefield measurements of 184 patients harboring low- (n=30) and high-grade gliomas (n=115), non-glial primary brain tumors (n=19), radiation necrosis (n=2), miscellaneous (n=10) and metastases (n=8), which corresponds to up to 15000 spectra for a given test. The statistical differences in fluorophore abundances between classes were determined and visualized using dimensionality reduction techniques, including principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE). Three machine-learning models were trained to classify tumor type (12 classes), grade (3 classes), and glioma margins (3 classes). Five algorithms were tested with varying hyperparameters for each classification task. We explored whether PCA projection onto five different axes than fluorophore abundances can provide more information for visualization and classification. The abundances of the five a priori fluorophore spectra matched or outperformed the five optimal PCA components for all classification tasks. These five axes capture 96-99% of the variance in the dataset. Using random forests and multilayer perceptrons, the classifiers achieved average test accuracies of 74-82%, 79%, and 81%, respectively. All five fluorophore abundances varied between tumor margin type as well as between grades (p &amp;lt; 0.01). For tissue type, at least four of five fluorophore abundances were found to be significantly different (p &amp;lt; 0.01) between all classes. These results demonstrate the differing contribution of fluorophores in different tissue classes tissue, as well as the five fluorophores value as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy

BackgroundOpportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.MethodsNineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count.ResultsCBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r2 = 0.46, p = 0.004, r2 = 0.45, p = 0.004, respectively), TUNEL cell count (r2 = 0.34, p = 0.02) and predicted both initial insult (r2 = 0.62, p = 0.002) and outcome group (r2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r2 = 0.34, p = 0.01 and r2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r2 = 0.43, p = 0.01).ConclusionOptical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model.ImpactThis study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome.Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

Improved in vivo optical coherence tomography imaging of animal peripheral nerves using a prism nerve holder.

Modern optical volumetric imaging modalities, such as optical coherence tomography (OCT), provide enormous information about the structure, function, and physiology of living tissue. Although optical imaging achieves lateral resolution on the order of the wavelength of light used, and OCT achieves axial resolution on a similar micron scale, tissue optical properties, particularly high scattering and absorption, limit light penetration to only a few millimeters. In addition, in vivo imaging modalities are susceptible to significant motion artifacts due to cardiac and respiratory function. These effects limit access to artifact-free optical measurements during peripheral neurosurgery to only a portion of the exposed nerve without further modification to the procedure. We aim to improve in vivo OCT imaging during peripheral neurosurgery in small and large animals by increasing the amount of visualized nerve volume as well as suppressing motion of the imaged area. We designed a nerve holder with embedded mirror prisms for peripheral nerve volumetric imaging as well as a specific beam steering strategy to acquire prism and direct view volumes in one session with minimal motion artifacts. The axially imaged volumes from mirror prisms increased the OCT signal intensity by over a 1.25-mm imaging depth in tissue-mimicking phantoms. We then demonstrated the new imaging capabilities in visualizing peripheral nerves from direct and side views in living rats and minipigs using a polarization-sensitive OCT system. Prism views have shown nerve fascicles and vasculature from the bottom half of the imaged nerve which was not visible in direct view. We demonstrated improved OCT imaging during neurosurgery in small and large animals by combining the use of a prism nerve holder with a specifically designed beam scanning protocol. Our strategy can be applied to existing OCT imaging systems with minimal hardware modification, increasing the nerve tissue volume visualized. Enhanced imaging depth techniques may lead to a greater adoption of structural and functional optical biomarkers in preclinical and clinical medicine.

Optical Monitoring in Neonatal Seizures.

Background: Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics. Aim: To perform a systematic review of optical biomarkers to identify changes in cerebral haemodynamics and metabolism during the pre-ictal, ictal, and post-ictal phases of neonatal seizures. Method: A systematic search was performed in eight databases. The search combined the three broad categories: (neonates) AND (NIRS) AND (seizures) using the stepwise approach following PRISMA guidance. Results: Fifteen papers described the haemodynamic and/or metabolic changes observed with NIRS during neonatal seizures. No randomised controlled trials were identified during the search. Studies reported various changes occurring in the pre-ictal, ictal, and post-ictal phases of seizures. Conclusion: Clear changes in cerebral haemodynamics and metabolism were noted during the pre-ictal, ictal, and post-ictal phases of seizures in neonates. Further studies are necessary to determine whether NIRS-based methods can be used at the cot-side to provide clear pathophysiological data in real-time during neonatal seizures.

Low frequency power in cerebral blood flow is a biomarker of neurologic injury in the acute period after cardiac arrest

AimCardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01–0.1 Hz) in cerebral haemodynamics has been used in functional magnetic resonance imaging as a marker of neuronal activity. Our hypothesis was that increased LFP in cerebral blood flow (CBF) would be correlated with improvements in invasive measures of neurologic health. MethodsWe adapted the use of LFP for to monitoring of CBF with diffuse correlation spectroscopy. We asked whether LFP (or other optical biomarkers) correlated with invasive microdialysis biomarkers (lactate-pyruvate ratio – LPR – and glycerol concentration) of neuronal injury in the 4 h after return of spontaneous circulation in a swine model of paediatric cardiac arrest (Sus scrofa domestica, 8–11 kg, 51% female). Associations were tested using a mixed linear effects model. ResultsWe found that higher LFP was associated with higher LPR and higher glycerol concentration. No other biomarkers were associated with LPR; cerebral haemoglobin concentration, oxygen extraction fraction, and one EEG metric were associated with glycerol concentration. ConclusionContrary to expectations, higher LFP in CBF was correlated with worse invasive biomarkers. Higher LFP may represent higher neurologic activity, or disruptions in neurovascular coupling. Either effect may be harmful in the acute period after cardiac arrest. Thus, these results suggest our methodology holds promise for development of new, clinically relevant biomarkers than can guide resuscitation and post-resuscitation care.Institutional protocol number: 19-001327.

Towards Engineering Early Vascular Aging as the Biomarker of Metabolic Dysregulations in Complex Posttraumatic Stress Disorder Due to Childhood Sexual Abuse: A Lyfas Study

Background and Objective: Repetitive Childhood sexual abuse (CSA) often predisposes CPTSD which affects mental and cardiometabolic health. Early vascular aging (EVA) is the hallmark sign of adverse cardiometabolic health. Smartphone-based cardiovascular optical biomarker (COB) instrumentLyfas captures such risk non-invasively. This study aims to examine two EVA-related COBs such as Arterial stiffness index (ASI) and Vascular aging (VA)in CPTSD and CPTSD with CSA in adults. Method: An IoT-enabled platform is created for the study. Interested visitors enroll and take the CPTSD Check List – Civilian type (PCL-C) self-tests and also fill out an online form related to CSA. The cohorts scoring high for PCL-C encompass Case-I (males and females 189 and 188, respectively)while those having a positive history of CSAcompriseCase-II (males and females 11 and 12, respectively). An equal number of control groups are also considered for each case. All the four groups take Lyfas tests and the COBs are captured from their index finger capillaries using the smartphone’s camera sensor, light, and the technique called arterial photoplethysmography. The EVA-COBs are validated against the ultrasound Doppler and then correlated with the PCL-C scores statistically. Results: The study observes (i) higher anxiety levels in both the genders with the mean SD2/SD1 (anxiety biomarker) in males and females (p-values &lt;0.05), (ii) Lyfas ASI and Doppler’s Acceleration index (AI%) are yielding to each other in males and females, respectively, (iii) High VA in both the genders (p-values &lt;0.05), which are &gt;20, (iv) Mean PCL-C scores of 32.06 and 38 in males and females refer to moderately high CPTSD (p-values &lt;0.05) in the population, (v) risk of EVA in females is twice of males. Conclusions:Lyfas is an assistive biomedical application that can screen and monitor mental health-related cardiometabolic health in the vulnerable population.The VA and ASI are two useful biomarkers. Authors also have linked the biological disorders leading to social aberrations in the CPTSD cases with or without the history of CSA and inferred that CSA further deteriorates the natural coping mechanism of CPTSD.

Modeling the risk of insulin resistance in borderline personality disorder with romantic pathological jealousy in females: A Lyfas empirical study

Borderline Personality Disorder (BPD) with Romantic pathological jealousy (rPAJ) influences the heart rate variability (HRV) and its cardiovascular optical biomarkers (COBs), which the Lyfas mobile application captures through smartphones. The COBs surrogate insulin resistance (IR), a marker of cardiometabolic risks. The paper aims to non-invasively study the IR risk in BPD-rPAJ affected females. Personality-based Questionnaire (PBQ) and the Multidimensional jealousy scale (MDJS) and Lyfas tests were taken by the participants under psychologists’ supervision. The VO2Max (COB of heart-lung coherence after stressful exercise), LF/HF (COB of IR), and Arterial stiffness index (ASI), a marker of early vascular aging, are chosen as the IR biomarkers. HRVScore, SD1/SD2, and pNN50 are chosen as the mood, anxiety, and sleep (MAS) biomarkers. Finally, each of the MAS-IR COBs is regressed to examine the causality. The R2 value &gt;= 25 is considered the significant causative. Furthermore, the relative risk (RR) is computed between significant MAS-IR COBs. The study observes that HRVScore and pNN50 possess high causal relationships with ASI (R2 = 47% and 25%, respectively). The RR shows an increased risk of premature arterial stiffness (PAS) with mood dysregulations (RR = 10.5, p 0.02) and sleep issues (RR = 135, p 0.19) when compared to the baseline population. The study concludes that mood dysregulations and poor sleep quality are associated with a high risk of IR in females suffering from BPD-rPAJ disorder. The onset of the deterioration of their arterial health starts as early as an average of five-and-a-half years.