Microsecond Scale Research Articles

Thermal effects and deformation mechanisms in abrasive waterjet machining: insights from Ti-6Al-4V alloy for broader applications

As a novel cold machining method, abrasive waterjet machining (AWJM) has significant potential for processing titanium-based materials such as Ti-6Al-4V alloy. However, the thermal effects and material deformation mechanisms of AWJM remain challenging to explain. This study introduces a six-colour blackbody radiation pyrometry method that successfully monitors transient high temperatures during AWJM. The results revealed that temperatures during AWJM were not negligible, reaching up to 3602.08 K, leading to material solidification and oxidation. The flash temperature exhibited transient and continuously oscillating characteristics at the microsecond scale. The combined mechanical and thermal loads created three distinct regions: the jet impact zone (elongated grains, oxide-based compositions, and material melting), the heat-affected zone (larger grains), and the base material zone. In the jet impact zone, a pronounced temperature gradient formed on the surface, promoting grain refinement. However, as the distance from the impact zone increases, the extent of grain refinement diminishes, leading to larger grain sizes. The higher kernel average misorientation values observed in and near the impact zone indicated that high-temperature conditions were insufficient for complete recrystallisation, either because of inadequate diffusion or the short duration of the elevated temperatures. This study reveals the thermal and material deformation mechanisms involved in the AWJM process. This establishes a foundational understanding of the processing of titanium-based and other heat-sensitive materials, ultimately contributing to enhanced overall material performance.

Electromagnetic Model of K‐Changes

AbstractK‐changes are observed as step‐like increases in the thundercloud electric fields. The K‐changes occur in the late part of intra‐cloud lightning or during negative cloud‐to‐ground lightning between return strokes. It has been shown that the processes leading to K‐changes initiate in the decayed part of a positive leader channel and propagate toward the flash origin. They are often accompanied by microsecond‐scale electric field pulses. We introduce a new model to simulate processes leading to the K‐changes in cloud‐to‐ground lightning. Our method is based on the full solution of Maxwell's equations coupled to Poisson's equation for the thundercloud charge structure. To model the K‐changes, we gradually increase the decayed channel conductivity. The modeled current wavefront propagates due to the K‐processes downward along a vertical channel and completely attenuates before reaching the ground. We derive the evolution of the linear charge densities and the scalar electric potential along the channel leading to K‐changes. We model electrostatic step‐like changes in the measured electric field together with the approximate rates and amplitudes of the microsecond scale pulses. Step‐like changes increase their amplitudes with the length of the simulated channel and with a higher conductivity of the channel. The microsecond‐scale pulse waveshapes depend mainly on the propagation velocity of the current wave, and the time scale of the conductivity increase. We show that our modeled waveforms are in a good agreement with observations conducted in Florida.

Numerical Investigations into the Homogenization Effect of Nonlinear Composite Materials on the Pulsed Electric Field

Pulsed power equipment is often characterized by high energy density and field intensity. In the presence of strong electric field intensity, charge accumulation within insulators exacerbates electric field non-uniformity, leading to potential insulation breakdown, thereby posing a significant threat to the safe operation of pulsed power equipment. In this manuscript, we introduce nonlinear composite materials with field-dependent conductivity and permittivity to adaptively regulate the distribution of the pulsed electric field in insulation equipment. Finite-element modeling and analysis of the needle-plate electrodes and high-voltage bushing are carried out to comprehensively investigate the non-uniformity of the distribution of the electric field and the homogenization effect of various nonlinear materials in the presence of pulsed excitations of different timescales. Numerical results indicate that the involvement of nonlinear composite materials significantly improves the electric field distribution under pulse excitations. In addition, variations in the rising time of the pulses affect the maximum electric field intensity within the insulators considerably, but for pulses of nanosecond and microsecond scales, the tendencies are the opposite. Finally, via the simulations of the bushing, we illustrate that some measures proposed for improving the uniformity of the electric field under low frequencies, e.g., increasing the length of the electric field equalization layer and the distance of the underside of the electric field equalization layer from the grounding screen, are still effective for the homogenization of pulsed electric field.

Energy regulation of impulse current generator modulated DC arc discharge

AbstractThis paper proposes a method of impulse current generator modulated DC arc by combining the advantages of pulse and the RF to solve the low electron energy problem of direct current arc. Through experimental analyzing the electrical, spectral, and optical characteristics of the arc, the effect of impulse current generator (ICG) on improving electron energy is discussed. The results show that the ICG consumes more energy to enhance the strength of arc discharge, and therefore electron energy is increased in a microsecond scale. In addition, it is found that the electron energy of the arc discharge can be adjusted by varying inductance, capacitance, and discharge tube: increasing the inductance or capacitance can increase the electron energy firstly and then decrease it. In adjusting the three adjustable components, adjusting the inductor is the most effective method, followed by adjusting the capacitor, and adjusting the repetition frequency has the least effect. The reason is discussed, and it is believed that the results are related to leakage inductance and distributed capacitance.

Modeling stable cavitation of coated microbubbles: A framework integrating smoothed dissipative particle dynamics and the Rayleigh-Plesset equation.

Coated microbubbles are widely used in medical applications, particularly in enhanced drug and gene delivery. One of the mechanisms underlying these applications involves the shear stress exerted on the cell membrane by acoustic microstreaming generated through cavitation bubbles. In this study, we develop a novel simulation approach that combines the smooth dissipative particle dynamics (SDPD) simulation method with numerical modeling of the Rayleigh-Plesset-like equation in an ad hoc manner to simulate stable cavitation of microbubbles at microsecond and micrometer scales. Specifically, the SDPD method is utilized to model fluid dynamics, while the Rayleigh-Plesset-like equation is employed to describe bubble dynamics. Adopting a 1.5 μm coated microbubble driven by ultrasound with a frequency of 2MHz and a pressure of 500kPa as a representative example, we observe a high-velocity microstreaming pattern emerging around the bubble on a very small scale of a few micrometers after only a few microseconds. These spatiotemporal scales may pose challenges for experimental observation. The formation of this microstreaming arises from the opposing motion of the fluid layer next to the bubble and the fluid layers further away. Furthermore, our simulations reveal high shear stress levels of thousands of Pascals exerted on a wall located a few micrometers from the bubble. This contrasts with the shear stress values of a few Pascals calculated from theoretical models in the literature, which do not incorporate radial streaming into their theories. The implications of our results for bubble cavitation-induced pore formation on the cell membrane are discussed in some details.

Time structures of proton pencil beam scanning delivery on a microsecond scale measured with a pixelated semiconductor detector Timepix3.

The time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non-invasive technique based on scattered particle tracking. A pixelated semiconductor detector, AdvaPIX-Timepix3, with a temporal resolution of 1.56ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high-flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty. The uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub-milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7µs and 1ms repetition time for the synchrocyclotron accelerator. The AdvaPIX-Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files.

Parametric study of the laser energy absorption in high-power laser beam welding

Laser energy absorption on the keyhole wall is decisive for the thermodynamic behavior and the resultant weld properties in the high-power laser beam welding process. However, its highly transient nature on a microsecond scale makes the quantitative analysis challenging. In this paper, the influence of the relevant welding parameters on laser energy absorption is studied statistically by utilizing multiphysical modeling, in which the three-dimensional transient keyhole dynamics and thermo-fluid flow are calculated. A dynamic mesh adaption technique and a localized level-set-based ray-tracing method are employed to improve the model accuracy further. The results show that the focus position has a remarkable effect on the time-averaged laser absorption, and in contrast, the laser energy distribution regime is only slightly influenced by the welding speed in the studied parameter range (1.5–3.0 m/min). The absorption ratio of the laser energy on the keyhole front wall decreases with increasing welding speed and increases with upward-moving focus positions. The comparison between the calculated results and the experimental measurements ensures the validity of the proposed model.

4D Single-particle tracking with asynchronous read-out single-photon avalanche diode array detector

Single-particle tracking techniques enable investigation of the complex functions and interactions of individual particles in biological environments. Many such techniques exist, each demonstrating trade-offs between spatiotemporal resolution, spatial and temporal range, technical complexity, and information content. To mitigate these trade-offs, we enhanced a confocal laser scanning microscope with an asynchronous read-out single-photon avalanche diode array detector. This detector provides an image of the particle’s emission, precisely reflecting its position within the excitation volume. This localization is utilized in a real-time feedback system to drive the microscope scanning mechanism and ensure the particle remains centered inside the excitation volume. As each pixel is an independent single-photon detector, single-particle tracking is combined with fluorescence lifetime measurement. Our system achieves 40 nm lateral and 60 nm axial localization precision with 100 photons and sub-millisecond temporal sampling for real-time tracking. Offline tracking can refine this precision to the microsecond scale. We validated the system’s spatiotemporal resolution by tracking fluorescent beads with diffusion coefficients up to 10 μm2/s. Additionally, we investigated the movement of lysosomes in living SK-N-BE cells and measured the fluorescence lifetime of the marker expressed on a membrane protein. We expect that this implementation will open other correlative imaging and tracking studies.

Effect of Lipid Bilayer Anchoring on the Conformational Properties of the Cytochrome P450 2D6 Binding Site.

Human cytochrome P450 (CYP) proteins metabolize 75% of small-molecule pharmaceuticals, which makes structure-based modeling of CYP metabolism and inhibition, bolstered by the current availability of X-ray crystal structures of CYP globular catalytic domains, an attractive prospect. Accounting for this broad metabolic capacity is a combination of the existence of multiple different CYP proteins and the capacity of a single CYP protein to metabolize multiple different small molecules. It is thought that structural plasticity and flexibility contribute to this latter property; therefore, incorporating diverse conformational states of a particular CYP is likely an important consideration in structure-based CYP metabolism and inhibition modeling. While all-atom explicit-solvent molecular dynamics simulations can be used to generate conformational ensembles under biologically relevant conditions, existing CYP crystal structures are of the globular domain only, whereas human CYPs contain N-terminal transmembrane and linker peptides that anchor the globular catalytic domain to the endoplasmic reticulum. To determine whether this can cause significant differences in the sampled binding site conformations, microsecond scale all-atom explicit-solvent molecular dynamics simulations of the CYP2D6 globular domain in an aqueous environment were compared with those of the full-length protein anchored in a POPC lipid bilayer. While bilayer-anchoring damped some structural fluctuations in the globular domain relative to the aqueous simulations, none of the affected residues included binding site pocket residues. Furthermore, clustering of molecular dynamics snapshots based on either pairwise binding site pocket RMSD or volume differences demonstrated a lack of separation of snapshots from the two simulation conditions into different clusters. These results suggest the substantially simpler and computationally cheaper aqueous simulation approach can be used to generate a relevant conformational ensemble of the CYP2D6 binding site for structure-based metabolism and inhibition modeling.

Interactions of a Novel Anthracycline with Oligonucleotide DNA and Cyclodextrins in an Aqueous Environment.

Berubicin, a chemotherapy medication belonging to the class of anthracyclines, is simulated in double-stranded DNA sequences and cyclodextrins in an aqueous environment via full-atom molecular dynamics simulations on the time scale of microseconds. The drug is studied in both the neutral and protonated states so as to better comprehend the role of its charge in the formed complexes. The noncovalent berubicin-DNA and berubicin-cyclodextrin complexes are investigated in detail, paying special attention to their thermodynamic description by employing the double decoupling method, the solvent balance method, the weighted solvent accessible surface model, and the linear interaction energy method. A novel approach for extracting the desolvation thermodynamics of the binding process is also presented. Both the binding and desolvation Gibbs energies are decomposed into entropic and enthalpic contributions so as to elucidate the nature of complexation and its driving forces. Selected structural and geometrical properties of all the complexes, which are all stable, are analyzed. Both cyclodextrins under consideration are widely utilized for drug delivery purposes, and a comparative investigation between their bound states with berubicin is carried out.

MemPol: polling-based microsecond-scale per-core memory bandwidth regulation

In today’s multiprocessor systems-on-a-chip, the shared memory subsystem is a known source of temporal interference. The problem causes logically independent cores to affect each other’s performance, leading to pessimistic worst-case execution time analysis. Memory regulation via throttling is one of the most practical techniques to mitigate interference. Traditional regulation schemes rely on a combination of timer and performance counter interrupts to be delivered and processed on the same cores running real-time workload. Unfortunately, to prevent excessive overhead, regulation can only be enforced at a millisecond-scale granularity. In this work, we present a novel regulation mechanism from outside the cores that monitors performance counters for the application core’s activity in main memory at a microsecond scale. The approach is fully transparent to the applications on the cores, and can be implemented using widely available on-chip debug facilities. The presented mechanism also allows more complex composition of metrics to enact load-aware regulation. For instance, it allows redistributing unused bandwidth between cores while keeping the overall memory bandwidth of all cores below a given threshold. We implement our approach on a host of embedded platforms and conduct an in-depth evaluation on the Xilinx Zynq UltraScale+ ZCU102, NXP i.MX8M and NXP S32G2 platforms using the San Diego Vision Benchmark Suite.

Isomer-sourced structure iteration methods for in silico development of inhibitors: Inducing GTP-bound NRAS-Q61 oncogenic mutations to an “off-like” state

The NRAS-mutant subset of melanoma represent some of the most aggressive and deadliest types associated with poor overall survival. Unfortunately, for more than 40 years, no therapeutic agent directly targeting NRAS mutations has been clinically approved. In this work, based on microsecond scale molecular dynamics simulations, the effect of Q61 mutations on NRAS conformational characteristics is revealed at the atomic level. The GTP-bound NRAS-Q61R and Q61K mutations show a specific targetable pocket between Switch-II and α-helix 3 whereas the NRAS-Q61L non-polar mutation category shows a different targetable pocket. Moreover, a new isomer-sourced structure iteration method has been developed for the in silico design of potential inhibitor prototypes for oncogenes. We show the possibility of a designed prototype HM-387 to target activated NRAS-Q61R and that it can gradually induce the transition from the activated NRAS-Q61R to an “off-like” state.

Dynamic characteristics of a coaxial magnetic switch modulating pulse forming networks.

Pulsed power generators utilizing magnetic switch technology within the 100ns scale have become widespread for surface treatment, high power microwave generation, and food processing, in which the dynamic characteristics of the magnetic switch perform an important function. The saturation process, electric field between layers, and energy loss are closely associated with the applied time scale of the magnetic core, which affects the dynamic characteristics of the switch. However, compared with the study within the microsecond scale, the dynamic characteristics of magnetic switches within the 100ns scale have not been studied in depth. In this paper, the dynamic characteristics of a coaxial magnetic switch modulating pulse forming networks (PFNs) are studied via both field-loop co-simulation and scaled experimental test. It is found that increasing PFN section number (Ns) leads to an acceleration in the saturation process of the core, which helps understand the switch performance of the magnetic core more clearly. With respect to a specific magnetic switch based on a ferromagnetic core, it is quantitatively analyzed that increasing Ns from 1 to 10 leads to a 16.1% reduction in core saturation time (tsat), a 13.4% increase in eddy loss (EET), and a 5.7% rise in maximum interlamination field strength (Emax) under the 100ns scale; however, tsat is reduced by 19.3%, EET increases by 5.2%, and Emax rises by 2.3% under the microsecond scale. The results could provide a design reference for magnetic switches in pulsed power generators.

Effects of C479W Mutation on the Structure and Function of Band 3 Protein

Band 3, or anion exchanger 1 (AE1), is one of the indispensable transmembrane proteins involved in effective respiratory processes in the human body, mainly responsible for the exchange of bicarbonate and chloride ions on the plasma membrane of red blood cells. However, the effect of related gene mutations on Band 3 ion transport is not fully understood. In this work, we used all-atom molecular dynamics (MD) simulations to systematically investigate the effects of the mutation from cysteine (C) to tryptophan (W) at site 479 in Band 3 on the structure of Band 3 and its interaction with anions. We studied the kinetics of wild-type (WT) and mutant Band 3 interactions with bicarbonate and chloride ions on the microsecond scale. The results showed that the mutation at site 479 affected the stability of Band 3 structure and the distribution of anions, and changed the affinity of anions to different parts of Band 3. These findings provide some insights into the structural and functional effects of gene mutations in Band 3 and contribute to understanding Band 3 anion exchange.

Rapid optical switching of latched electrical resistance in a high-T c superconducting tape

We report microsecond timescale switching between the superconducting and normal states of commercially manufactured high-Tc superconducting wires using optical radiation to heat the conductor above Tc. The achieved voltages and switching times have significant implications for a new class of thermal switches. The report contains experimental data for photo-induced microsecond scale voltage transients as well as numerical analysis of heat propagation through the material in response to optical radiation. The microbridges are etched into commercially manufactured coated conductors and submerged in liquid nitrogen. By varying the magnitude of the transport current, two different optical responses are identified. At low transport currents, short-lived voltage transients occur, transitioning to persistent latching once the current is increased above a threshold value. The microbridge, therefore, behaves as a fast opening and closing switch when carrying low currents or an optically latched thyristor at high currents. This is understood to occur due to critical current suppression as a result of heating from the optical pulse. Optically induced heating reduces the superconducting volume fraction, and Joule heating due to the transport current interaction with the high temperature superconducting occurs, which either causes short-lived or stable self-heating normal regions dependent on the magnitude of the transport current. This study is concluded with an estimate of the energy necessary to drive the microbridge into the resistive state. The observed behavior can potentially be utilized as a switching element in superconducting transformer rectifiers where high frequency switch operation is required.

Molecular mechanism underlying SNARE-mediated membrane fusion enlightened by all-atom molecular dynamics simulations

The SNAP receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin mediate neurotransmitter release by forming tight SNARE complexes that fuse synaptic vesicles with the plasma membranes in microseconds. Membrane fusion is generally explained by the action of proteins on macroscopic membrane properties such as curvature, elastic modulus, and tension, and a widespread model envisions that the SNARE motifs, juxtamembrane linkers, and C-terminal transmembrane regions of synaptobrevin and syntaxin-1 form continuous helices that act mechanically as semirigid rods, squeezing the membranes together as they assemble ("zipper") from the N to the C termini. However, the mechanism underlying fast SNARE-induced membrane fusion remains unknown. We have used all-atom molecular dynamics simulations to investigate this mechanism. Our results need to be interpreted with caution because of the limited number and length of the simulations, but they suggest a model of membrane fusion that has a natural physicochemical basis, emphasizes local molecular events over general membrane properties, and explains extensive experimental data. In this model, the central event that initiates fast (microsecond scale) membrane fusion occurs when the SNARE helices zipper into the juxtamembrane linkers which, together with the adjacent transmembrane regions, promote encounters of acyl chains from both bilayers at the polar interface. The resulting hydrophobic nucleus rapidly expands into stalk-like structures that gradually progress to form a fusion pore, aided by the SNARE transmembrane regions and without clearly discernible intermediates. The propensity of polyunsaturated lipids to participate in encounters that initiate fusion suggests that these lipids may be important for the high speed of neurotransmitter release.

Helical Content Correlations and Hydration Structures of the Folding Ensemble of the B Domain of Protein A.

The B domain of protein A (BdpA), a small three-helix bundle, folds on a time scale of a few microseconds with heterogeneous native and unfolded states. It is widely used as a model for understanding protein folding mechanisms. In this work, we use structure-based models (SBMs) and atomistic simulations to comprehensively investigate how BdpA folding is associated with the formation of its secondary structure. The energy landscape visualization method (ELViM) was used to characterize the pathways that connect the folded and unfolded states of BdpA as well as the sets of structures displaying specific ellipticity patterns. We show that the native state conformational diversity is due mainly to the conformational variability of helix I. Helices I, II, and III occur in a weakly correlated manner, with Spearman's rank correlation coefficients of 0.1539 (I and II), 0.1259 (I and III), and 0.2561 (II and III). These results, therefore, suggest the highest cooperativity between helices II and III. Our results allow the clustering of partially folded structures of folding of the B domain of protein A on the basis of its secondary structure, paving the way to an understanding of environmental factors in the relative stability of the basins of the folding ensemble, which are illustrated by the structural dependency of the protein hydration structures, as computed with minimum-distance distribution functions.

Closing the loop: High-speed robotics with accelerated neuromorphic hardware.

The BrainScaleS-2 system is an established analog neuromorphic platform with versatile applications in the diverse fields of computational neuroscience and spike-based machine learning. In this work, we extend the system with a configurable realtime event interface that enables a tight coupling of its distinct analog network core to external sensors and actuators. The 1,000-fold acceleration of the emulated nerve cells allows us to target high-speed robotic applications that require precise timing on a microsecond scale. As a showcase, we present a closed-loop setup for commuting brushless DC motors: we utilize PyTorch to train a spiking neural network emulated on the analog substrate to control an electric motor from a sensory event stream. The presented system enables research in the area of event-driven controllers for high-speed robotics, including self-supervised and biologically inspired online learning for such applications.

Temperature-dependent elasticity of DNA, RNA, and hybrid double helices

Nucleic acid double helices in their DNA, RNA, and DNA-RNA hybrid form play a fundamental role in biology and are main building blocks of artificial nanostructures, but how their properties depend on temperature remains poorly understood. Here, we report thermal dependence of dynamic bending persistence length, twist rigidity, stretch modulus, and twist-stretch coupling for DNA, RNA, and hybrid duplexes between 7°C and 47°C. The results are based on all-atom molecular dynamics simulations using different force field parameterizations. We first demonstrate that unrestrained molecular dynamics can reproduce experimentally known mechanical properties of the duplexes at room temperature. Beyond experimentally known features, we also infer the twist rigidity and twist-stretch coupling of the hybrid duplex. As for the temperature dependence, we found that increasing temperature softens all the duplexes with respect to bending, twisting, and stretching. The relative decrease of the stretch moduli is 0.003–0.004/°C, similar for all the duplex variants despite their very different stretching stiffness, whereas RNA twist stiffness decreases by 0.003/°C, and smaller values are found for the other elastic moduli. The twist-stretch couplings are nearly unaffected by temperature. The stretching, bending, and twisting stiffness all include an important entropic component. Relation of our results to the two-state model of DNA flexibility is discussed. Our work provides temperature-dependent elasticity of nucleic acid duplexes at the microsecond scale relevant for initial stages of protein binding.

Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.

Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes. However, this technique only provides two-dimensional information; crucial depth information, such as the location of malignancy below the tissue surface, is not provided. We developed a depth sensing imaging technique using light detection and ranging (LiDAR) time-of-flight (TOF) technology to sense the depth of target tissue while overcoming the influence of tissue optical properties and fluorescent probe concentration. The technology is based on a large-format (), binary, gated, single-photon avalanche diode (SPAD) sensor with an 18ps time-gate step, synchronized with a picosecond pulsed laser. The fast response of the sensor was developed and tested for its ability to quantify fluorescent inclusions at depth and optical properties in tissue-like phantoms through analytical model fitting of the fast temporal remission data. After calibration and algorithmic extraction of the data, the SPAD LiDAR technique allowed for sub-mm resolution depth sensing of fluorescent inclusions embedded in tissue-like phantoms, up to a maximum of 5mm in depth. The approach provides robust depth sensing even in the presence of variable tissue optical properties and separates the effects of fluorescence depth from absorption and scattering variations. LiDAR TOF fluorescence imaging using an SPAD camera provides both fluorescence intensity images and the temporal profile of fluorescence, which can be used to determine the depth at which the signal is emitted over a wide field of view. The proposed tool enables fluorescence imaging at a higher depth in tissue and with higher spatial precision than standard, steady-state fluorescence imaging tools, such as intensity-based near-infrared fluorescence imaging, optical coherence tomography, Raman spectroscopy, or confocal microscopy. Integration of this technique into a standard surgical tool could enable rapid, more accurate estimation of resection boundaries, thereby improving the surgeon's efficacy and efficiency, and ultimately improving patient outcomes.