Phase Function Research Articles

Elevated plasma progranulin levels in the acute phase are correlated with recovery of left ventricular function in the chronic phase in patients with acute myocardial infarction.

Progranulin is a secreted glycoprotein that regulates inflammation and wound healing. However, plasma progranulin levels in the acute phase and their clinical significance in patients with acute myocardial infarction (AMI) remain to be elucidated. We aimed to investigate the relationship between the increase in plasma progranulin levels in the acute phase and the recovery of left ventricular function in the chronic phase in AMI patients. Eighteen AMI patients were followed up for 6 months. Blood samples were collected from the antecubital vein on day 0 (on admission) and day 7 in the acute phase. The control group consisted of patients without significant coronary artery stenosis, as assessed by cardiac catheterization (n = 16). Plasma progranulin levels were measured by enzyme-linked immunosorbent assay. Echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI to evaluate left ventricular ejection fraction using the modified Simpson's method. Plasma progranulin levels in the AMI group on day 0 (69.5 ± 24.6 ng/mL) were similar to those in the control group (84.2 ± 47.1 ng/mL). There was a significant increase in progranulin levels in the AMI group on day 7 (104.2 ± 52.0 ng/mL) compared with day 0. The increase in plasma progranulin levels in the acute phase was positively correlated with the increase in left ventricular ejection fraction between the acute and chronic phases. Among various factors, only plasma progranulin levels were favorably correlated with left ventricular functional recovery in the chronic phase. The increase in plasma progranulin levels in the acute phase may serve as a predictive biomarker and a contributer for the recovery of left ventricular function in the chronic phase in patients with AMI.

Chorus Organization in a Neotropical Forest Cicada

In many species of animals, males aggregate in particular locations and produce calls to attract searching females for reproduction. One striking feature of such choruses is synchronization. On a scale of hours, choruses are often concentrated at particular times of day, such as dawn or dusk. On a scale of seconds, males may also synchronize the rhythm of their calls with one another. While synchronized calling at this scale suggests benefits acting at the collective level, competitive interactions between males to attract females can also lead to synchronized calling as an epiphenomenon. Why males in some species synchronize the rhythm of their calls is still debated, and more work is needed to understand the evolution of this behavior. I investigated chorus organization in the Emerald cicada (Zammara smaragdula), a Neotropical forest cicada in southern Belize, to explore these issues. Choruses in this species occurred at dawn and dusk and, occasionally, during daytime. There was no evidence for synchronization in the rhythm of calls among males, as bouts of collective calling occurred after quiet intervals of variable rather than fixed durations. The temporal aggregation of calls in this species thus probably emerged from competitive interactions among males to attract females. The degree of temporal overlap in the calls of males during a chorus varied as a function of chorus phase and time of day, suggesting flexibility in chorus organization, perhaps in relation to temporal variations in factors such as the number of calling cicadas, the number of predators present or ambient temperature during a chorus.

A Compositional Approach to the Simulation of Queuing Systems with Random Parameters

A general approach to modeling random service processes under conditions of disturbances and uncertainty of the initial data is substantiated. A compositional approach to constructing simulation models of queuing with parametric uncertainty based on phase-type distributions and phase functions is proposed. The calculation and comparison of the characteristics of the developed simulation models with analytical solutions were carried out to confirm their effectiveness and accuracy. The problems of uncertainty of the initial data and their impact on the modeling of service systems are highlighted. The importance of taking into account parametric uncertainty in simulation models is emphasized in order to increase their adequacy and applicability in practice. The study includes a description of a general approach to modeling random service processes with uncertainty, as well as methodological foundations for the application of phase distributions and functions in compositional modeling. Four classes of service models are considered, differing in the type of integral core and phase function, which makes it possible to implement a variety of random service processes, taking into account their characteristics and conditions of their occurrence. The analysis of a model with an exponential integral core and various types of phase functions is carried out, which demonstrates the flexibility and wide possibilities of the proposed compositional approach to the study and modeling of service systems. The results of simulation modeling are presented, confirming analytical studies and showing the applicability and effectiveness of the developed approach in the construction and analysis of models of service systems with random parameters. The practical significance of the compositional method for the design and modernization of information and computing systems at various stages of their development, taking into account the uncertainty of the initial data, is noted. The work is focused on the development of simulation methods for queuing systems and opens up new prospects for their research and optimization in conditions of uncertainty of initial parameters.

Accelerated Simulations Reveal Physicochemical Factors Governing Stability and Composition of RNA Clusters.

Under certain conditions, RNA repeat sequences phase separate, yielding protein-free biomolecular condensates. Importantly, RNA repeat sequences have also been implicated in neurological disorders, such as Huntington's disease. Thus, mapping repeat sequences to their phase behavior, functions, and dysfunctions is an active area of research. However, despite several advances, it remains challenging to characterize the RNA phase behavior at a submolecular resolution. Here, we have implemented a residue-resolution coarse-grained model in LAMMPS─that incorporates both the RNA sequence and structure─to study the clustering propensities of protein-free RNA systems. Importantly, we achieve a multifold speedup in the simulation time compared to previous work. Leveraging this efficiency, we study the clustering propensity of all 20 nonredundant trinucleotide repeat sequences. Our results align with findings from experiments, emphasizing that canonical base-pairing and G-U wobble pairs play dominant roles in regulating cluster formation of RNA repeat sequences. Strikingly, we find strong entropic contributions to the stability and composition of RNA clusters, which is demonstrated for single-component RNA systems as well as binary mixtures of trinucleotide repeats. Additionally, we investigate the clustering behaviors of trinucleotide (odd) repeats and their quadranucleotide (even) counterparts. We observe that odd repeats exhibit stronger clustering tendencies, attributed to the presence of consecutive base pairs in their sequences that are disrupted in even repeat sequences. Altogether, our work extends the set of computational tools for probing RNA cluster formation at submolecular resolution and uncovers physicochemical principles that govern the stability and composition of the resulting clusters.

МЕТОД МОНТЕ-КАРЛО ДЛЯ РАСЧЕТА ХАРАКТЕРИСТИК СВЕТОВЫХ ПОЛЕЙ В МОРСКОЙ ВОДЕ

The development of numerical methods for solving the integro-differential radiation transfer equation remains a relevant task. Among them, we can highlight the Monte Carlo method, which is in demand in various niches of modern ocean optics. The purpose of this work is a clear and concise presentation of the basics of the forward Monte Carlo method of light fields modeling in seawater, accompanied by a detailed description of its software implementation. The basics of the method are described, the procedures for choosing the type of interaction, the mean free path and the direction of photon motion are described. A simple case is considered, corresponding to an infinitely distant point source of unpolarized light, the absence of atmospheric influence, a smooth air-seawater interface, and the absence of stratification of inherent optical properties. In this case, realistic values of the absorption and scattering coefficients were used, calculated in accordance with the Case 1 model for a chlorophyll concentration of 1 μg/L, and a strongly elongated Henyey-Greenstein phase function with the parameter g = 0.95. The Fresnel reflection of light from the air-seawater interface was taken into account. The relative errors in the values of the diffuse attenuation coefficient for downward irradiance K d and the diffuse reflectance R, calculated in the spectral range of 400–700 nm using 106 photons, in comparison with the HydroLight results were 1.5 % and 0.4 %, respectively. Spectral calculation on one core of a 2017 Intel Core i5-8250U mobile processor in MATLAB takes 6 minutes. An assessment of the choice of the optimal number of photons required to obtain the desired quantities with a given accuracy was made. The implemented method is useful for becoming familiar with the basic principles used to numerically solve the radiative transfer equation in seawater using statistical methods and is used in the “Ocean Optics” course, taught by the author to 4th year students of the Department of Thermohydromechanics of the Ocean at MIPT.

Oscillatory integrals and weighted gradient flows

We investigate estimating scalar oscillatory integrals by integrating by parts in directions based on (x_{1} \partial_{x_1}f(x) ,\dots, x_{n} \partial_{x_n}f(x)) , where f(x) is the phase function. We prove a theorem which provides estimates that are uniform with respect to linear perturbations of the phase and investigate some consequences. When the phase function is quasi-homogeneous the theorem gives estimates for the associated surface measure Fourier transforms that are generally not too far off from being sharp. In addition, the theorem provides a new proof, up to endpoints, that the well-known oscillatory integral estimates of Varchenko when the Newton polyhedron of the phase function is nondegenerate extend to corresponding bounds for surface measure Fourier transforms when the index is less than 1/2 . A sharp version of this was originally proven by the author [J. Funct. Anal. 262 (2012), no. 5, 2314–2348].

Effectiveness of Vibrapep (OPEP) on Pulmonary functions in phase one of cardiac rehabilitation-A Randomized controlled trial

Background and Aims: According to the WHO report 2022, coronary artery disease is the most prevalent cardiac disease worldwide. Impaired respiratory muscle function, increased secretions and reduced vital capacity are pulmonary complications commonly associated with CABG and Valve replacement surgeries. The purpose of this study was to compare the effect of Vibrapep and standard phase one of cardiac rehabilitation exercises on pulmonary functions. Methods: A Randomized Controlled Trial was conducted on 46 participants. Participants were randomly allocated into two groups, Vibrapep and phase one of cardiac exercises were given to Group A (n = 23), while Group B (n = 23) received only phase one cardiac rehabilitation exercises. The intervention was administered for twice a day for 5 days. Outcome measures such as Sputum volume, maximal inspiratory and expiratory pressure, thoracic expansion, SPO2 level, blood pressure and Peak expiratory flow rate were evaluated at baseline and on 5th day of the study. Results: Wilcoxon test of within-group analysis revealed statistically significant improvements in all parameters for both the interventional and control groups (p<0.05*), except in diastolic blood pressure, whereas, between group analysis done using Mann Whitney U test also showed statistical improvement in both groups on all parameters with (p<0.05*). Conclusion: Vibrapep exhibited to be an effective bronchial hygiene therapy in phase one of cardiac rehabilitation with respect to enhancing pulmonary functions such as sputum reduction, chest expansion, improved respiratory pressure’s, Peak Expiratory Flow Rate along with Cardiac rehabilitation.

Comparative Planetology of Magnetic Effects in Ultrahot Jupiters: Trends in High-resolution Spectroscopy

Ultrahot Jupiters (UHJs), being the hottest class of exoplanets known, provide a unique laboratory for testing atmospheric interactions with internal planetary magnetic fields at a large range of temperatures. Thermal ionization of atmospheric species on the dayside of these planets results in charged particles becoming embedded in the planet’s mostly neutral wind. The charges will resist flow across magnetic field lines as they are dragged around the planet and ultimately alter the circulation pattern of the atmosphere. We model this process to study this effect on high-resolution emission and transmission spectra in order to identify observational signatures of the magnetic circulation regime that exist across multiple UHJs. Using a state-of-the-art kinematic MHD/active drag approach in a 3D atmospheric model, we simulate three different UHJs with and without magnetic effects. We postprocess these models to generate high-resolution emission and transmission spectra and explore trends in the net Doppler shift as a function of phase. In emission spectra, we find that the net Doppler shift before and after secondary eclipse can be influenced by the presence of magnetic drag and the wavelength choice. Trends in transmission spectra show our active drag models consistently produce a unique shape in their Doppler shift trends that differs from the models without active drag. This work is a critical theoretical step to understanding how magnetic fields shape the atmospheres of UHJs and provides some of the first predictions in high-resolution spectroscopy for observing these effects.

The Dependence of Joy’s Law and Mean Tilt as a Function of Flux Emergence Phase

Data from the Michelson Doppler Imager (MDI) and Helioseismic and Magnetic Imager (HMI) are analyzed from 1996 to 2023 to investigate tilt angles (γ) of bipolar magnetic regions and Joy’s law for Solar Cycles 23 and 24 and a portion of Cycle 25. The HMI radial magnetic field (B r ) and MDI magnetogram (B los) data are used to calculate (γ) using the flux-weighted centroids of the positive and negative polarities. Each active region (AR) is only sampled once. The analysis includes only Beta (β)-class ARs since computing γ of complex ARs is less meaningful. During the emergence of the ARs, we find that the average tilt angle ( γ¯ ) increases from 3.°30 ± 0.75 when 20% of the flux has emerged to 6.°79° ± 0.66 when the ARs are at their maximum flux. Cycle 24 has a larger average tilt, γ¯24 =6.67 ± 0.66, than Cycle 23, γ¯23 = 5.11 ± 0.61. No significant difference is found in the slope of Joy’s law or γ¯ when sampling the ARs at the time of maximum flux or central meridian crossing. There are persistent differences in γ¯ in the hemispheres, with the Sun's southern hemisphere having higher γ¯ in Cycles 23 and 24, but the uncertainties are such that these differences are not statistically significant.

DSIFNet: Implicit Feature Network for Nasal Cavity and Vestibule Segmentation from 3D Head CT

This study is dedicated to accurately segment the nasal cavity and its intricate internal anatomy from head CT images, which is critical for understanding nasal physiology, diagnosing diseases, and planning surgeries. Nasal cavity and it’s anatomical structures such as the sinuses, and vestibule exhibit significant scale differences, with complex shapes and variable microstructures. These features require the segmentation method to have strong cross-scale feature extraction capabilities. To effectively address this challenge, we propose an image segmentation network named the Deeply Supervised Implicit Feature Network (DSIFNet). This network uniquely incorporates an Implicit Feature Function Module Guided by Local and Global Positional Information (LGPI-IFF), enabling effective fusion of features across scales and enhancing the network's ability to recognize details and overall structures. Additionally, we introduce a deep supervision mechanism based on implicit feature functions in the network's decoding phase, optimizing the utilization of multi-scale feature information, thus improving segmentation precision and detail representation. Furthermore, we constructed a dataset comprising 7116 CT volumes (including 1,292,508 slices) and implemented PixPro-based self-supervised pretraining to utilize unlabeled data for enhanced feature extraction. Our tests on nasal cavity and vestibule segmentation, conducted on a dataset comprising 128 head CT volumes (including 34006 slices), demonstrate the robustness and superior performance of proposed method, achieving leading results across multiple segmentation metrics.

Measurement of circular intensity differential scattering (CIDS) from single optically trapped biological particles

The circular intensity differential scattering (CIDS), which is the normalized Mueller matrix element -S14/S11, has been measured from single biological particles as a function of scattering angle. CIDS is valuable for its potential in detecting chiral particles that may include the helical structures of DNA or RNA molecules in biological samples, and as such is a potential method for detecting biological particles. Optical trapping is employed to levitate single particles within a custom-designed elliptical reflector for CIDS measurements. The advantage of optical levitation in light-scattering measurements is that single particles can be suspended in air with sufficient working distance to prevent interference from the suspending apparatus. To measure the phase function, the reflector is used to collect the angle-dependent scattering signals. We demonstrated that we can obtain two-dimensional angular optical scattering (TAOS) patterns that cover a wide angular range from single levitated particles. These TAOS patterns are generated using 532 nm illumination of left-handed and right-handed circular polarizations and recorded from trapped single particles (silica, English Oak, Ragweed, Mulberry, Glycine, and l-Aspartic acid).

Auto Aligning, Error-Compensated Broadband Collimated Transmission Spectroscopy.

Broadband spectral measurements of the ballistic transmission of scattering samples are challenging. The presented work shows an approach that includes a broadband system and an automated adjustment unit for compensation of angular distortions caused by non-plane-parallel samples. The limits of the system in terms of optimal transmission and detected forward scattering influenced by the scattering phase function are investigated. We built and validated a setup that measures the collimated transmission signal in a spectral range from 300 nm to 2150 nm. The system was validated using polystyrene spheres and Mie calculations. The limits of the system in terms of optimal transmission and detected forward scattering were researched. The optimal working parameters of the system, analyzed by simulations using the Monte Carlo method, show that the transmission should be larger than 10% and less than 90% to allow for a reliable measurement with acceptable errors caused by noise and systematic errors of the system. The optimal transmission range is between 25% and 50%. We show that the phase function is important when considering the accuracy of the measurement. For strongly forward-scattering samples, errors of up to 80% can be observed, even for a very small numerical aperture of 6.6·10-4, as used in our experimental system. We also show that errors increase with optical thickness as the ballistic transmission decreases and the multiscattered fraction increases. In addition, errors caused by multiple reflections in the sample layer were analyzed and also classified as relevant for classical absorption spectroscopy.

Relationship between changes in renal function after acute phase of tafamidis administration and left ventricular diastolic function at mid-term follow-up in transthyretin cardiac amyloidosis

Abstract Background A large number of heart failure (HF) patients present with various degrees of renal dysfunction, known as cardio-renal syndrome. Renal impairment in HF patients is also associated with an independent risk factor for morbidity and mortality. Transthyretin (TTR) amyloidosis (ATTR) is characterized by disintegrated liver-derived TTR that accumulates as amyloid fibrils in the myocardium, leading to initially presenting as left ventricular (LV) hypertrophy and LV diastolic dysfunction. Although there is no proven therapy for patients with ATTR cardiomyopathy (ATTR-CM), tafamidis meglumine, a TTR stabilizer, has been associated with favorable outcomes. Although the kidneys are also an important organ where amyloid deposition occurs, the effect of tafamidis on renal function and its relationship to LV diastolic function is unclear. Purpose The purpose of this study was to investigate the relationship between changes in renal function after the acute phase of tafamidis administration and LV diastolic function at mid-term follow-up in patients with ATTR-CM. Methods We studied 56 patients with biopsy-proven ATTR-CM who were treated with tafamidis. All patients underwent blood examinations before and 45.6 ± 23.0 days after the acute phase of tafamidis administration. Echocardiography was performed before and 15.6 ± 9.8 months after the mid-term of tafamidis administration. The primary endpoint was defined as a composite of cardiovascular death or HF hospitalization for 5.0 years. Results Twelve patients had improved renal function as assessed by estimated glomerular filtration rate in the acute phase after tafamidis administration, while 44 patients deteriorated. In the group with improved renal function in the acute phase after tafamidis administration, pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus (E’) and left atrial volume index (LAVI) tended to improve at mid-term follow-up compared to the non-improved group. (E’: 0.8 ± 1.7 cm/s vs. 0.2 ± 1.1 cm/s, p=0.127, LAVI: -8.7 ± 12.0 mL/m2 vs. 0.2 ± 16.8 mL/m2, p=0.093). Furthermore, Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with improved renal function in the acute phase after tafamidis administration tended to be lower than those without (log-rank P=0.137). Conclusions The improvement of renal function in the acute phase after tafamidis administration was associated with the improvement of LV diastolic function at mid-term follow-up, leading to favorable outcome. Our findings may provide new insights for the management of patients with ATTR-CM.

Atrial function after cardioversion in patients with persistent atrial fibrillation

Abstract Background After cardioversion for persistent atrial fibrillation (AF), restitution of normal left atrial (LA) function is said to need several days to recover. However, in previous studies, the evaluation of LA function was only used transesophageal or transthoracic echocardiography. During catheter ablation (CA) for AF, pulmonary venous (PV) blood flow can be measured accurately using an intracardiac echocardiogram (ICE). The atrial systolic PV regurgitation (PVa) wave measured by ICE is a good indicator of LA contractility because it reflects the active contraction of the LA. Purpose This study aims to investigate the LA function in the hyperacute phase and the factors which affect after cardioversion. Methods 40 AF patients (18 paroxysmal AF, 22 persistent AF) who underwent CA were enrolled. PVa wave was measured twice before RFCA and after the procedure using intracardiac ultrasound. Voltage map of the LV was obtained using the CARTO system at the end of the session, and the percentage of low voltage area which was determined area as less than 0.1mV in the mapped LA surface area (LVA%) was calculated. Results Preoperative PVa was 1.61 ± 0.09 m/sec in the paroxysmal AF group (PaAF), and no PVa was observed in the persistent AF group (PeAF). Postoperative PVa were comparable between PaAF (0.18±0.06 m/sec) and PeAF (0.18±0.07 m/sec). Then, the PeAF were divided into 2 groups based on LVA% in the anterior area, posterior area, and total LA area (cutoff 1,5 and 10%, respectively). In the anterior lower LVA% group, PVa were significantly increased (0.20 ± 0.07 m/sec) after defibrillation compared with the anterior higher LVA% group (0.14 ± 0.06 m/sec; P=0.02), whilst no difference was observed when it was divided in the posterior wall or overall. Conclusion Even in PeAF, LA function improves to the same degree as in the PaAF immediately after cardioversion, and the posterior wall LVA, including posterior wall isolation, may not affect LA function.

Pedal Reaction Forces and Electromyography Responses Indicate Eccentric Contractions During Motorized Cycling in a Rat Model of Incomplete Spinal Cord Injury.

Motorized cycling (MC) is utilized as an alternative to traditional exercise in individuals who are unable to perform voluntary movements post-spinal cord injury. Although rodent models of MC often show more positive outcomes when compared with clinical studies, the cause of this difference is unknown. We postulate that biomechanical differences between rats and humans may contribute to this discrepancy. To begin to test this theory, we examined pedal reaction forces and electromyography (EMG) of hindlimb muscles as a function of cycle phase and cadence in a rat model of MC. We found that higher cadences (≥30 RPM) increased EMG and force, with higher forces observed in animals with contusion injuries as compared with transections. To further investigate the forces, we developed a technique to separate rhythmic (developed with the motion of the pedals) from nonrhythmic forces. Rhythmic forces resulted from induced eccentric muscle contractions that increased (amplitude and prevalence) at higher cadences, whereas nonrhythmic forces showed the opposite pattern. Our results suggest that muscle activity during MC in rats depends on the stretch reflex, which, in turn, depends on the rate of muscle lengthening that is modulated by cadence. Additionally, we provide a framework for understanding MC that may help translate results from rat models to clinical use in the future.

Single-photon 3D imaging of room-scale scenes through scattering media

Light detection and ranging (LiDAR) utilizes eye-safe laser beams to perceive the world in three-dimensional (3D) detail, offering machines and computers with an accurate representation of their surroundings. This technology is widely employed in metrology, environmental monitoring, archaeology, and robotics. However, the presence of scattering media in the optical path, such as fog, dust, or translucent plates, will cause light scattering and occlude direct observation of the scene. To address scattering distortions, conventional methods require the prior knowledge of the scattering media or the target location, limiting their applicability outside the laboratory. Leveraging single-photon sensitivity and time-gated technology, single photon LiDAR emerges as a promising solution for active scattering imaging. In this study, we construct a single-photon LiDAR prototype and demonstrate its capability to perform 3D imaging of a room-scale (1.1 m × 1.1 m × 4 m) hidden scene behind a ground glass diffuser located approximately 50 meters away from the imaging system. Incorporating phase function to construct the forward model and considering the system-induced temporal broadening, our method is capable of producing reliable results behind various scattering layers. The results indicate potential applications such as remote non-invasive testing and detection in challenging scenarios.

An IQ Industry Perspective on Informing Dosing Recommendations in Patients With Renal Impairment.

The IQ CPLG Organ Impairment WG conducted a survey to understand how various IQ member companies develop dosing recommendations for patients with renal impairment. Eighteen IQ member companies participated in the survey. The survey results were summarized by the working group in light of the regulatory renal impairment guidance documents as well as recent publications from the pharmaceutical industry and nephrology community. There were two important learnings from the survey: (i) pharmaceutical companies do not use a consistent methodology to assess renal function in their drug development programs. (ii) there has been significant improvement in predicting how kidney function affects drug pharmacokinetics (PK) and thus dose recommendations. Applying model-based methods such as population PK, physiologically-based PK (PBPK), and virtual controls has enabled earlier prediction of how kidney function influences PK, leading to the participation of more patients with impaired kidney function in Phase 2 and 3 trials.

Higher-order stochastic averaging for investigating a vehicle suspension system with nonlinear damping and stiffness

The paper deals with a quarter-car model with nonlinear damping and stiffness under white noise base excitation using the higher-order stochastic averaging method for analyzing approximate responses. Recently, a novel higher-order averaging procedure has been developed to find analytically the first-, second-, and third-order stationary joint probability density functions (PDF) of amplitude and full phase by solving the corresponding Fokker-Planck-Kolmogorov (FPK) equation, and it will be extended to the nonlinear quarter-car model. Accordingly, the mean-square responses such as the displacement, and velocity of the sprung mass can be obtained analytically. The influences of excitation intensity on the dynamic responses, as well as the variations of linear and nonlinear damping, are analyzed. A very satisfactory agreement is found between the accuracy of the solutions corresponding to higher-order stochastic averaging and that of Monte Carlo simulation.

Phase-Sensitive Fluorescence Image Correlation Spectroscopy.

Fluorescence lifetime imaging microscopy is sensitive to molecular interactions and environments. In homo-dyne frequency-domain fluorescence lifetime imaging microscopy, images of fluorescence objects are acquired at different phase settings of the detector. The detected intensity as a function of detector phase is a sinusoidal function that is sensitive to the lifetime of the fluorescent species. In this paper, the theory of phase-sensitive fluorescence image correlation spectroscopy is described. In this version of lifetime imaging, image correlation spectroscopy analysis (i.e., spatial autocorrelation) is applied to successive fluorescence images acquired at different phase settings of the detector. Simulations of different types of lifetime distributions reveal that the phase-dependent density of fluorescent objects is dependent on the heterogeneity of lifetimes present in the objects. We provide an example of this analysis workflow to a cervical cancer cell stained with a fluorescent membrane probe.

Study protocol: Cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury -CAPCOG-TBI.

Moderate-severe traumatic brain injury (msTBI) stands as a prominent etiology of adult disability, with increased risk for cognitive impairment and dementia. Although some recovery often occurs within the first year post-injury, predicting long-term cognitive outcomes remains challenging, partly due to the significant pathophysiological heterogeneity of TBI, including acute cerebrovascular injury. The primary aim of our recently funded study, cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury (CAPCOG-TBI), is to determine if acute cerebrovascular dysfunction after msTBI measured using multimodal non-invasive neuromonitoring is associated with cognitive outcome at 1-year post-injury. This longitudinal observational study will be conducted at two Level 1 trauma centers in Texas, USA, and will include adult patients with msTBI, and/or mild TBI with neuroimaging abnormalities. Multimodal cerebral vascular assessment using transcranial Doppler and cerebral near-infrared spectroscopy (NIRS) will be conducted within 7-days of onset of TBI. Longitudinal outcomes, including cognitive/functional assessments (Glasgow Outcome Scale and Patient-Reported Outcomes Measurement Information System), cerebral vascular assessment, and imaging will be performed at follow-ups 3-, 6-, and 12-months post-injury. We aim to recruit 100 subjects with msTBI along with 30 orthopedic trauma controls (OTC). This study is funded by National Institute of Neurological Disease and Stroke (NINDS) and is registered on Clinicaltrial.org (NCT06480838). We anticipate that msTBI patients will exhibit impaired cerebrovascular function in the acute phase compared to the OTC group. The severity of cerebrovascular dysfunction during this stage is expected to inversely correlate with cognitive and functional outcomes at 1-year post-injury. Additionally, recovery from cerebrovascular dysfunction is expected to be linked to cognitive recovery. The results of this study could help to understand the contribution of cerebrovascular dysfunction to cognitive outcomes after TBI and pave the way for innovative vascular-focused interventions aimed at enhancing cognitive recovery and mitigating neurodegeneration following msTB. In addition, its focus toward personalized medicine to aid in the management and prognosis of TBI patients.