Fast Technique Research Articles

Multiple cross displacement amplification combined with nanoparticle-based lateral flow biosensor for rapid and sensitive detection of Epstein-Barr virus.

Epstein-Barr virus (EBV) is a highly dangerous virus that is globally prevalent and closely linked to the development of nasopharyngeal cancer (NPC). Plasma EBV DNA analysis is an effective strategy for early detection, prognostication and monitoring of treatment response of NPC. Here, we present a novel molecular diagnostic technique termed EBV-MCDA-LFB, which integrates multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow (LFB) to enable simple, rapid and specific detection of EBV. In the EBV-MCDA-LFB system, a set of 10 primers was designed for rapidly amplifying the highly conserved tandem repeat BamHI-W region of the EBV genome. Subsequently, the LFB facilitate direct assay reading, eliminating the use of extra instruments and reagents. The outcomes showed that the 65°C within 40 minutes was the optimal reaction setting for the EBV-MCDA system. The sensitivity of EBV-MCDA-LFB assay reached 7 copies per reaction when using EBV recombinant plasmid, and it showed 100% specificity without any cross-reactivity with other pathogens. The feasibility of the EBV-MCDA-LFB method for EBV detection was successfully validated by 49 clinical plasma samples. The complete detection process, consisting of rapid template extraction (15 minutes), MCDA reaction (65°C for 40 minutes), and LFB result reading (2 minutes), can be finalized within a 60-minutes duration. EBV-MCDA-LFB assay designed here is a fast, extremely sensitive and specific technique for detecting EBV in field and at the point-of-care (PoC), which is especially beneficial for countries and regions with a high prevalence of the disease and limited economic resources.

Chemical characterization and sensory properties of apple brandies aged with different toasted oak chips and ultra-high-pressure treatments

Aging is an important processing step of producing high quality apple brandy. In this study, apple brandies aged by traditional method and using three different toasted oak chips combined with or without ultra-high-pressure (UHP) treatment were prepared to compare their differences in chemical characterization and sensory properties. The results indicated that the brandies aged with toasted oak chip increased the levels of total acidity, volatile acidity and phenolic compounds. It also had the desirable color and taste. The brandy aged with toasted oak chip combined with UHP reached the highest levels of total acidity (1.06 g/L), total phenolic content (284.92 mg/L) and aromatic esters (49.37 %). Therefore, the aging with high toasted oak chip combined with UHP treatment could cut the traditional aging time to meet the same quality as traditional aging method. The results are very useful to develop a fast and efficient aging technique for brandy production.

Short-term results of tibial interference screw fixation for transtibial medial meniscus posterior root pull-out repair

BackgroundTo evaluate the technique of transtibial pull-out repair with tibial interference screw fixation for medial meniscus posterior root (MMPR) tear by reporting on short-term outcomes and complications. MethodsAll MMPR repairs performed between January 2019 and August 2021 (n = 70) were retrospectively screened regarding demographic data and surgical parameters. The patients were questioned for performed revision surgery, symptoms and complications. The Numeric Rating Scale (NRS) for pain, Lysholm Knee Score and International Knee Documentation Committee Subjective Knee Form (IKDC) questionnaires were used to evaluate clinical outcome. In cases of revision surgery for re-tear the mode of failure was intraoperatively classified (patients with re-tear were excluded from the clinical follow-up examination). The influence of demographic and treatment parameters (surgical and rehabilitation) on the incidence and mode of re-tear and clinical scores was evaluated. ResultsAfter 2.3 ± 0.7 years, 62 patients (88.6 %) were available for follow-up. There were no direct intra- or postoperative complications. No revision was performed due to symptoms related to the tibial fixation material. The mean surgery time was 33.5 ± 10.8 min. The overall re-tear rate was 17.7 % (11 patients) of whom 10 were treated surgically and one conservatively. Primary mode of failure was suture cut-out from the meniscus (70 %). The NRS, Lysholm Knee Score and subjective IKDC were obtained in 38 patients and improved from 6.8 ± 2.4, 40.1 ± 23.9 and 32.8 ± 16.3 to 2.2 ± 2.2, 80.5 ± 16.3 and 63.0 ± 13.9, respectively (all p < 0.001). No influence was observed from demographic and treatment parameters on re-tear rates or clinical Scores. ConclusionsTibial interference screw fixation is a fast and promising technique for MMPR transtibial pull-out repair. In the presented technique, utilizing non-absorbable locking sutures alongside tibial interfenrence screw fixation, the primary mode of failure was suture cut-out from the meniscus.

In vivo gene editing of CAMKIID: out with the bad and in with the good.

The ability to change an organism's DNA through gene editing is of great importance for the prevention and treatment of genetic and acquired diseases. Rapid progress has been made during the last decade due to the discovery and refinement of CRISPR/Cas9 as an accurate, fast, and reliable genome editing technique. In this issue of the JCI, Lebek et al. present the culmination from a line of work in the Olson laboratory focused on in vivo gene editing of CAMK2D. The paper presents a combined state-of-the-art gene therapy approach that demonstrates how gene therapy can yield cardioprotection in a mouse model and takes notable steps toward potential applicability in patients.

FROST-BRDF: A Fast and Robust Optimal Sampling Technique for BRDF Acquisition.

Efficient and accurate BRDF acquisition of real world materials is a challenging research problem that requires sampling millions of incident light and viewing directions. To accelerate the acquisition process, one needs to find a minimal set of sampling directions such that the recovery of the full BRDF is accurate and robust given such samples. In this article, we formulate BRDF acquisition as a compressed sensing problem, where the sensing operator is one that performs sub-sampling of the BRDF signal according to a set of optimal sample directions. To solve this problem, we propose the Fast and Robust Optimal Sampling Technique (FROST) for designing a provably optimal sub-sampling operator that places light-view samples such that the recovery error is minimized. FROST casts the problem of designing an optimal sub-sampling operator for compressed sensing into a sparse representation formulation under the Multiple Measurement Vector (MMV) signal model. The proposed reformulation is exact, i.e. without any approximations, hence it converts an intractable combinatorial problem into one that can be solved with standard optimization techniques. As a result, FROST is accompanied by strong theoretical guarantees from the field of compressed sensing. We perform a thorough analysis of FROST-BRDF using a 10-fold cross-validation with publicly available BRDF datasets and show significant advantages compared to the state-of-the-art with respect to reconstruction quality. Finally, FROST is simple, both conceptually and in terms of implementation, it produces consistent results at each run, and it is at least two orders of magnitude faster than the prior art.

Template-based target point localization for occlusion of the middle meningeal artery during evacuation of space-occupying chronic subdural hematoma.

Endovascular middle meningeal artery (MMA) occlusion may help reduce the risk of recurrence after burr hole evacuation of chronic subdural hematoma (cSDH) but carries an additional periprocedural risk and remains hampered by logistical and financial requirements. In this study, the authors aimed to describe a simple and fast technique for preoperative MMA localization to permit burr hole cSDH evacuation and MMA occlusion through the same burr hole. The authors performed a preclinical anatomical and prospective clinical study, followed by a retrospective feasibility analysis. An anatomical cadaver study with 33 adult human skulls (66 hemispheres) was used to localize a suitable frontal target point above the pterion, where the MMA can be accessed via burr hole trephination. Based on anatomical landmark measurements, the authors designed a template for projected localization of this target point onto the skin. Next, the validity of the template was tested using image guidance in 10 consecutive patients undergoing elective pterional craniotomy, and the feasibility of the target point localization for cSDH accessibility was determined based on hematoma localization in 237 patients who were treated for a space-occupying cSDH in the authors' department between 2014 and 2018. In the anatomical study, the mean perpendicular distance from the zygomatic process to the target point in the frontoparietal bone was 4.1 cm (95% CI 4-4.2 cm). The mean length along the upper margin of the zygomatic process from the middle of the external auditory canal to the point of the perpendicular distance was 2.3 cm (95% CI 2.2-2.4 cm). The template designed according to these measurements yielded high agreement between the template-based target point and the proximal MMA groove inside the frontoparietal bone (right 90.9%; left 93.6%). In the clinical validation, we noted a mean distance of 4 mm (95% CI 2.1-5.9 mm) from the template-based target point to the actual MMA localization. The feasibility analysis yielded that 95% of all cSDHs in this cohort would have been accessible by the new frontal burr hole localization. A template-based target point approach for MMA localization may serve as a simple, fast, reliable, and cost-effective technique for surgical evacuation of space-occupying cSDHs with MMA obliteration through the same burr hole in a single setting.

Application of the Fast Aging Technique to Wool Fabric Dyed with Natural Dyes Having Different Stains to Obtain Homogeneous Mimic Samples for Archaeological Measurements.

Application of the Fast Aging Technique to Wool Fabric Dyed with Natural Dyes Having Different Stains to Obtain Homogeneous Mimic Samples for Archaeological Measurements.

Madany closure: a novel technique for fascial closure in laparoscopic surgery

Background Laparoscopic surgery is now the accepted method of choice for practically all abdominal procedures. A number of trocar site closure techniques have been developed, but many of them are unaffordable and/or difficult to employ. Patients and methods The objective of this prospective interventional study is to assess the duration required to close the trocar site, the incidence of hemorrhage or other postoperative problems, and the safety and effectiveness of a novel fascial closure technique (the Madany closure). Patients who were eligible for laparoscopic cholecystectomy at the Aswan University Hospital’s General Surgery Department were included. Results One hundred and thirty patients were included in our study. Most of the participants were females, representing 93.08% of patients. The mean age of participants was 40.07±10.02 years, and the median (interquartile range) total time for the complete closure of the port site was 83.5 s (44.75 s). After the follow-up period of 6 months, no patient developed a trocar-site hernia. Conclusion The Madany closure technique provides a safe, fast, and effective technique for the closure of laparoscopic port sites.

MARALIXIBAT IN RAT PLASMA AND ITS PHARMACOLOGICAL STUDIES (BIO-ANALYTICAL METHOD DEVELOPMENT AND VALIDATION BY LC-MS)

The bio-analytical method development of Maralixibat using Elobixibat as an internal standard is a convenient, fast, accurate, and consistent new LC-MS technique and was validated. The present work explains the development of the LC-MS/MS bio-analytical method by RP-18(150x4.6 mm, 3.5µ) column and a binary mixture(0.1% formic acid &amp; methanol) of organic mobile phase in the ratio 60:40. By using liquid-liquid extraction process, these drugs are removed from rat plasma. The linearity in the standard curve was observed under the experimental concentration range. 10%-200% (6-12ng/ml) of Maralixibat. The calibration plots were linear with a regression coefficient of R2&gt; 0.999. Precision, Accuracy, Stability results, and Matrix effect were observed within the acceptable limit. The method is more accessible and effective for analyzing the sample in the body fluids. The work represents that Specificity, Suitability, Accuracy, and linearity parameters ideally agree with the USFDA guidelines and are efficiently practiced in rat plasma for pharmacokinetic studies

Stability study and development of the validated infrared spectrometric method for quantitative analysis of sevoflurane compared with the gas chromatographic method.

Sevoflurane, also called fluoromethyl ether, is an inhalation anesthetic agent used to initiate and maintain general anesthesia for adults and pediatric patients during surgical procedures. Several analytical methods have previously been applied to follow the properties and quality of sevoflurane, including mass spectrometry and gas chromatography methods. These methods are practically tedious and need sophisticated apparatus. In the present work, an attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometric method was used for the quantitative determination of sevoflurane which is characterized as a fast, accurate, and available technique for most pharmaceutical laboratories, besides the gas chromatographic method which is the most suitable for the detection of impurities. Sevoflurane is a liquid and it is applied directly on the glass top of the ATR-FTIR either as a concentrated solution or diluted with hexane as a diluent, which did not interfere with sample determination within the specified wavelength range of the IR spectrum, particularly the wavelength of the ethereal group at 1200 cm-1. This method can be applied to the identification test and quantitative assay of sevoflurane since it is validated for the precision, accuracy, reproducibility, and specificity in the analysis of sevoflurane as a pharmaceutical product. However, still, there is a need for a gas chromatographic method to detect the impurities and degradation products during the stability study of sevoflurane.

Effects of manufacturing parameters on mechanical interface properties of thin wood veneer laminates

This study explores fast manufacturing techniques for thin wood laminates made from European beech veneers and 1-component polyurethane adhesive. Manufacturing factors such as pressure and pressing time are investigated following well-established standards developed for fibre-reinforced materials (ASTM D5528 and ASTM D7905). Mode I and Mode II interlaminar fracture properties are calculated to quantify the effects of the different manufacturing techniques on the bond quality. It is found that pressing time and pressure can be minimised to 10 minutes and 0.1 MPa from 75 min and 1.0 MPa as suggested by the adhesive manufacturer, without reducing critical Mode I strain energy release rates of around 500 to 600 J/m2. However, the standard deviation of these properties increases with decreasing pressure and pressing time. Furthermore, the results show that while ASTM D5528 for Mode I testing can be used with thin wood veneer laminates, the ASTM D7905 for Mode II fracture testing is not directly applicable to these materials.

Evaluation of Stability and TLC Fingerprinting of the Artemether Component in Artemether-Lumefantrine Combination Suspension Formulations Available in Nigeria Pharmaceutical Market

Aim: Artemether is the main component of the artemisinin-based combination therapy (ACT), used in the management of malaria infection caused by Plasmodium falciparum. Hence, its stability and conformation to pharmacopeia standards are necessary for use. The study aimed to review the first-order derivative spectrophotometric method for simultaneous estimation of artemether and its derivatives in pure and combined formulations, and their stability profiles, then develop a simple, precise, and fast technique for their rapid physicochemical analysis.&#x0D; Methodology: Thin-layer chromatographic (TLC) Fingerprinting principles were used in the analysis. Artemether and its derivatives were spotted on the TLC chromatograms after adding 25 mL of the suspension to a mixture of 100 mL of distilled water and 4 mL of NaOH, extracting the mixture with 60 mL of dichloromethane (DCM), drying, and sonicating the residue with 20 mL of the solvent. It was centrifuged, and the clear supernatant was spotted on the TLC plates.&#x0D; Results: The color test results revealed the presence of the artemether compound in the reference standard as well as the six brands of suspensions (A, B, C, D, E, and F) utilized in the study. Artemether melting point was obtained between 86 - 89 °C; within the International Pharmacopeia specified range. The chromatograms of Artemether and derivatives showed Rf values of 0.25 (impurity A), 0.3 (artenimol impurity B), 0.35 (impurity C), 0.4 (α-artemether: impurity D), and 0.55 (artemether).&#x0D; Conclusion: The devised method can be applied to the routine quality control analysis of artemether-lumefantrine suspension in addition to existing analytical techniques.

Revealing the Rate-Limiting Electrode of Lithium Batteries at High Rates and Mass Loadings

Lithium-ion batteries with superior capacities and rate performance are needed due to the soaring demands for even higher energy and power device requirements. [1-2] However, the main hurdle on achieving this predominately results from poor rate performance of the electrode, related to thermodynamic limitations and slow kinetics. To determine the rate-limiting electrochemical processes in a NMC622 vs graphite cell, a methodology based upon the galvanic intermittent titration technique, for investigating the diffusion coefficient and rate kinetics from the observed overpotential at each electrode has been developed. Variable current densities have been used to simultaneously extract the thermodynamic and kinetic properties of each electrode with increasing mass loading. Graphite is observed to reach its thermodynamic limits quicker than NMC, due to the flat plateaus and overpotentials observed from the charge transfer kinetics and mass transport. At high rates and high mass loadings, the graphite electrode is responsible for limiting both lithium-ion diffusion and reaction rates in the full cell. Slow diffusion kinetics are caused by the transport of the electrolyte in the porous electrode, which limits the availability of lithium for reaction at the surface of the graphite. This current interrupt testing methodology is proposed as a fast single technique for comprehensively parameterizing the rate limitations observed in a full cell configuration [3].

Battery Venting Caused By Fast Charging

Lithium-ion batteries (LIBs) experience high risks of failure during unreasonable fast charging. Various degradation mechanisms inside the LIBs such as lithium (Li) plating, solid electrolyte interphase growth and electrolyte dry-out can undermine the electrochemical performance and induce massive gas generation alongside the operation. As a typical failure behaviour, venting occurs when the internal pressure of battery cell exceeds the safety threshold, releasing the gaseous products as well as depressurizing the cell. Recent studies1–3 of thermal runaway (TR) tests after fast charging have found that accumulated plated Li can react with electrolyte at elevated external temperatures, decreasing both self-heating and onset temperatures of TR. Yet, how fast-charging degradation will affect battery venting behaviours remains unclear.To answer this question, in this study, a series of fast charging experiments under controlled cooling as well as adiabatic TR tests were conducted with 51 Ah LiNi0.6Mn0.2Co0.2O2/graphite prismatic LIBs. The results showed that the prismatic battery underwent severe Li plating with over 30% capacity fade after 10 cycles of 4C charging. In the adiabatic TR tests, the aged batteries after 4C charging exhibited lower self-heating temperature and venting temperature as compared to the fresh batteries, by 51 ℃ and 34.4 ℃ respectively. This can be explained by the additional gas generation from the reaction between plated Li and electrolyte in the fast-charged batteries. Gas analyses of 120 ℃ hot-box tests for the degraded anodes with the electrolyte showed that the vented gas at the early venting stage primarily consisted of carbon dioxide, carbon monoxide and ethylene. The same charging protocols were then conducted in a natural convection thermal chamber with poor heat dissipation, where the temperature rise was much higher than those under forced convection as expected. Excessive cycling operations with off-limit charge rates (5C and 5.6C) were observed to directly cause battery swelling and venting without TR, and the temperature decreasing rates during rest after each charging process tend to slow down and even remain stable during a certain period of time. This indicates that the exothermic reaction between plated Li and electrolyte can be directly triggered by fast charging if heat removal is not effective enough. The findings provide useful insights into battery venting induced by fast charging, which can shed light on battery safety evaluation for fast charging techniques.Acknowledgements:This work is supported by the Faraday Institution BESAFE project (FIRG038), the Imperial College President’s PhD Scholarship Scheme (funded by EPSRC), the National Natural Science Foundation of China (Grant No. 52207241), China National Postdoctoral Program for Innovative Talents (grant no. BX20220171), China Postdoctoral Science Foundation (grant no. 2022M711760), and Shuimu Tsinghua Scholar Program (grant no. 2021SM130).

Fibronectin Conformations after Electrodeposition onto 316L Stainless Steel Substrates Enhanced Early-Stage Osteoblasts' Adhesion but Affected Their Behavior.

The implantation of metallic orthopedic prostheses is increasingly common due to an aging population and accidents. There is a real societal need to implement new metal implants that combine durability, good mechanical properties, excellent biocompatibility, as well as affordable costs. Since the functionalization of low-cost 316L stainless steel substrates through the successive electrodeposition of a polypyrrole film (PPy) and a calcium phosphate deposit doped with silicon was previously carried out by our labs, we have also developed a bio-functional coating by electrodepositing or oxidating of fibronectin (Fn) coating. Fn is an extracellular matrix glycoprotein involved in cell adhesion and differentiation. Impacts of either electrodeposition or oxidation on the structure and functionality of Fn were first studied. Thus, electrodeposition is the technique that permits the highest deposition of fibronectin, compared to adsorption or oxidation. Furthermore, electrodeposition seems to strongly modify Fn conformation by the formation of intermingled long fibers, resulting in changes to the accessibility of the molecular probes tested (antibodies directed against Fn whole molecule and Fn cell-binding domain). Then, the effects of either electrodeposited Fn or oxidized Fn were validated by the resulting pre-osteoblast behavior. Electrodeposition reduced pre-osteoblasts' ability to remodel Fn coating on supports because of a partial modification of Fn conformation, which reduced accessibility to the cell-binding domain. Electrodeposited Fn also diminished α5 integrin secretion and clustering along the plasma membrane. However, the N-terminal extremity of Fn was not modified by electrodeposition as demonstrated by Staphylococcus aureus attachment after 3 h of culture on a specific domain localized in this region. Moreover, the number of pre-osteoblasts remains stable after 3 h culture on either adsorbed, oxidized, or electrodeposited Fn deposits. In contrast, mitochondrial activity and cell proliferation were significantly higher on adsorbed Fn compared with electrodeposited Fn after 48 h culture. Hence, electro-deposited Fn seems more favorable to pre-osteoblast early-stage behavior than during a longer culture of 24 h and 48 h. The electrodeposition of matrix proteins could be improved to maintain their bio-activity and to develop this promising, fast technique to bio-functionalize metallic implants.

Saliva: An Emerging Adjunct Biomarker for Psoriasis –Trends, Scope and Relevance

Psoriasis is a widely prevalent chronic immuno inflammatory dermatological disease resulting from a complex and dynamic interplay of genetic, environmental, and immunological aetiologies. It manifests as characteristic erythematous psoriatic plaques visible to the naked eye, but prognostic biomarkers for disease monitoring and therapeutic effectiveness are still absent. Saliva is a biological fluid that, besides being critical to maintaining oral homeostasis, harbors various salivary microbiota and inflammatory markers. It can be easily collected, stored, and analyzed. Oral fluids offer an excellent advantage for biomarker study as they are non-invasive and fast techniques. Studies showed that the saliva of healthy individuals and those with psoriasis had differences in the levels of inflammatory cytokines, immunoglobulin A, and anti-oxidant biomarkers. In GCF, individuals with psoriasis showed higher levels of S100A8, IL-18, and sE-selectin than healthy individuals, independent of periodontal status. Oxidative stress(OS) is one of the pathogenetic factors of psoriasis. Thus levels of ROS and anti-oxidants can also become important factors in diagnosis.

A fast and time-efficient machine learning approach to dark matter searches in compressed mass scenario

Various analyses for searching for the signature of SUSY or exotic particles have been carried out by the experiments at CERN. These analyses made use of traditional cut and count methods. While this method has yielded promising results, it has been challenging in the region where the mass difference between SUSY particles is small. Deep learning is currently widely employed in most data analysis tasks, including high energy physics, and has made significant advances in almost all fields for collecting and interpreting huge data samples. In this paper, a fast and time-efficient classification technique is proposed, utilizing machine learning algorithms to distinguish dark matter signal from SM background in compressed mass spectra scenarios at a center-of-mass energy of 14 TeV. A classification model was built in a short amount of time using 2D histograms produced with less amount of data, effectively reducing computational costs through the transfer learning of pre-trained deep models while maintaining a high level of classification accuracy.

Sustainable microwave-assisted eutectic solvent extraction of polyphenols from vine pruning residues

This study describes the development of a laboratory-scale extraction method for polyphenols in vine pruning residues (VPR) using eutectic solvents and microwave heating. Grape VPR are an abundant waste biomass that is currently underexploited. VPR are rich in valuable extractives such as polyphenols, and their extraction with green and sustainable processes could constitute a promising valorization strategy. Microwave-assisted heating was used to obtain high extraction yields under relatively mild conditions. The performances of three eutectic solvents based on choline chloride and polyols (ethylene glycol, propylene glycol, and glycerol) were compared against a conventional water/ethanol solvent. These solvents were particularly effective at extracting stilbenoid polyphenols such as resveratrol, whose low water solubility usually requires high amounts of organic solvents. The solvent based on choline chloride and ethylene glycol provided the best results, and was chosen for further optimization by experimental design. Optimal performances were obtained under mild conditions (30 min, 85 °C). The effects of controlled amounts of water on the extraction efficiency of this solvent were also evaluated. Small amounts of water (approximately 10 %) led to an increase in the extraction yield, while higher water contents led to lower yields. Total polyphenol yields of up to 22 mg/g of substrate were obtained. The mild extraction conditions also allowed recovery of oligomeric stilbenoids such as ε-viniferin, which are often degraded when harsh conditions or water-based solvents are used. The developed method constitutes a fast and reliable technique for the recovery of polyphenols in VPR, and a promising laboratory-scale study of a potential valorization pathway for this biomass.

Polyfluoroalkyl Substances (PFASs) Detection Via Carbon Dots: A Review

PFASs are a class of highly persistent chemicals that are slowly infiltrating soils and waterways. Thus, there is a great need for fast, sensitive, and reliable techniques to detect PFASs. Conventional methods, such as LC-MS/SPE, allow high sensitivities. However, such methods can be complex and expensive. Considering this, it is not surprising that the scientific community has turned their attention to the search for alternatives. New types of PFAS sensors have been reported over the years, being generally part of three classes: optical, electrochemical, or hybrid sensors. Carbon dots (CDs) are new alternative fluorescent sensors that can present great affinity towards PFASs, while allowing for a fast response and promising sensitivity and selectivity. Furthermore, CDs have more attractive properties than traditional fluorophores and even metal-based nanomaterials that make them better candidates for sensing applications. Thus, CDs display great potential for permitting a fast and accurate quantification of PFASs. This review aims to serve as a basis for the future development and optimization of CD-based fluorescent sensors for PFASs.

Robust and fast stochastic 4D Flow Vector-field signature technique for quantifying composite flow dynamics from 4D Flow MRI: Application to left atrial flow in atrial fibrillation

4D flow MRI is an emerging imaging modality that maps voxel-wise blood flow information as velocity vector fields that is acquired in 7-dimensional image volumes (3 spatial dimensions + 3 velocity directions + time). Blood flow in the cardiovascular system is often complex and composite involving multiple flow dynamics and patterns (e.g., vortex flow, jets, stagnating flow) that occur and interact simultaneously. The spectrum of such complex flow dynamics is embedded in the velocity vector field dynamics derived from 4D Flow MRI. However, current flow metrics cannot fully measure high-dimensional vector-field data and embedded complex composite flow data. Instead, these methods need to break down the vector-field data into secondary scalar fields of individual flow components using fluid dynamics operators. These methods are gradient-based and sensitive to data uncertainties, and only focus on individual flow components of the overall composite flow, therefore potentially underestimating the severity of overall flow changes associated with cardiovascular diseases. To address these limitations, in MICCAI 2021, we introduced a novel comprehensive stochastic 4D Flow vector-field signature technique that works directly on the entire spatiotemporal velocity vector field. This technique uses efficient stochastic gradient-free interrogation of multi-million flow vector-pairs per patient to derive the patient's unique flow profile of the complex composite flow alterations and in real-time processing. The signature technique's probabilistic gradient-free formulation should allow for highly robust quantification despite inherent errors in 4D flow MRI acquisitions. Here, we extend the application of the 4D flow vector-field signature technique to the left atrium to analyze complex composite flow changes in patients with atrial fibrillation. In 128 subjects, we performed extensive sensitivity testing and determined that the vector-field signature technique is highly robust to typical sources of data uncertainties in 4D flow MRI: degradation in spatiotemporal resolution, added gaussian noise, and segmentation errors. We demonstrate the excellent generalizability of the stochastic convergence from the aorta to the left atrium and between different 4D Flow MRI acquisition protocols. We compare the robustness of our technique to existing advanced flow quantification metrics of kinetic energy, vorticity, and energy loss demonstrating a superior performance of up-to 14-fold. Our results show the potential diagnostic and clinical utility of our signature technique in identifying distinctly altered composite flow signatures in atrial fibrillation patients independent of existing flow metrics.