Dynamic Microvascular Monitoring with MOBILE: Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities

Dynamic Microvascular Monitoring with MOBILE: Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Dynamic Microvascular Monitoring with MOBILE: Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities Yizhi Liang, Wei Li, Xue Bai, Peiqian He, Yachao Zhang, Qi Zhang, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7154196/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jan, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Microcirculation monitoring is crucial for evaluating cardiovascular health and detecting organ dysfunction early, but existing bedside imaging techniques often cannot provide sufficient resolution and depth for dynamic assessment during natural physiological activities. Here, we present MOBILE (Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities), a novel photoacoustic imaging system that allows unrestricted microcirculatory monitoring with 40 µm resolution and penetration depth of 1 cm, allowing stratified visualization of dynamic vascular responses. This platform features an ultracompact fibre-optic sensor capable of omnidirectional ultrasound-based detection across a large bandwidth (0.3–80 MHz). The compact design of the system facilitates point-of-care monitoring through seamless integration with portable devices or existing clinical systems. Through a comprehensive evaluation of the patient’s haemodynamic parameters, MOBILE reveals distinct dynamic responses of vessels at different tissue depths, from superficial microvessels to deep subcutaneous vessels, capturing vessel-specific changes in diameter, haemoglobin concentration, and tissue oxygenation during numerous physiological challenges. This platform offers new possibilities for understanding microcirculatory responses and improving critical care management through high-resolution vessel monitoring. Biological sciences/Biological techniques/Imaging/Optical imaging Physical sciences/Optics and photonics/Optical techniques/Imaging and sensing Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The microcirculation, an intricate network of small blood vessels, serves as an important conduit for maintaining tissue functionality and metabolic activities through the dynamic regulation of the local blood supply 1 – 3 . Understanding the dynamics of the microcirculation during natural physiological activities is crucial, as the most significant microcirculatory adaptations occur in response to exercise, postural changes, and environmental stimuli. Moreover, microcirculatory dysfunction is increasingly recognized as an early indicator of multiple pathological conditions, including cardiovascular diseases, sepsis, and diabetes; therefore, continuous assessment of microcirculatory dynamics could aid in both early diagnosis and therapeutic monitoring 4 – 10 . However, comprehensive assessment of these dynamics remains technically challenging, as it simultaneously requires high spatiotemporal resolution, adequate imaging depth, and continuous monitoring capabilities during unrestricted movement. Current imaging technologies are unable to meet all these requirements: conventional modalities such as CT and MRI, while offering whole-body scanning capabilities, are impractical for continuous monitoring because of operational constraints; microbubble contrast agent-based ultrasound allows only intermittent visualization 11 – 13 ; and optical approaches, including video microscopy 14 and optical coherence tomography 15 , 16 , are fundamentally limited in terms of either penetration depth or spatial resolution. Photoacoustic imaging has emerged as a promising approach to address these challenges by combining optical excitation with ultrasonic detection, allowing high-resolution visualization of vascular structures at clinically relevant depths 17 – 23 . While conventional photoacoustic systems have demonstrated effectiveness in analysing haemodynamics 24 – 28 and characterizing the microcirculation under various pathological conditions 29 – 32 , their reliance on bulky ultrasound transducer arrays has limited applications primarily to stationary diagnostic imaging tasks, such as breast cancer detection 33 , 34 . Recent developments in small 35 , wearable photoacoustic devices 36 represent progress towards dynamic monitoring, but current systems can only visualize a few isolated vessels, which is unsuitable for achieving a comprehensive assessment of the microvasculature. In this study, we introduce MOBILE (Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities), a novel approach for imaging the microcirculation that employs a miniaturized photoacoustic probe based on a compact fibre-optic ultrasound sensor. Our sensor leverages isotropic vibrations within an optical fibre to achieve omnidirectional, broadband (0.3–80 MHz) ultrasound detection and exceptional sensitivity. Through these technical advancements, MOBILE allows visualization of vessels spanning multiple scales (40 µm to 1.5 mm diameter) within the dermis and subcutaneous tissues up to a depth of 1 cm with high resolution. The compact sensor design—including a sensing area 300-times smaller than that of conventional piezoelectric transducers—facilitates versatile implementation in both handheld and wearable formats while maintaining high performance across a wide range of angles. We demonstrate the clinical utility of MOBILE through comprehensive monitoring of the peripheral microcirculation during various physiological challenges, revealing vessel-specific dynamics in terms of haemoglobin concentration, diameter, and oxygen saturation across the vascular tree. Notably, our system allows the simultaneous characterization of distinct responses across vessel sizes and depths, from superficial capillaries to deep subcutaneous vessels, providing novel insights into the heterogeneous behaviour of the microcirculation during natural physiological activities. The results of this study bridge a critical gap in our understanding of vessel-resolved microcirculatory dynamics and their role in systemic haemodynamic regulation. Results MOBILE system design and performance characterization Figure 1 presents our MOBILE system for dynamic microvascular imaging. The miniaturized design is based on a fibre-optic ultrasound sensor positioned horizontally along the z-axis, with linear or curvilinear scanning performed along the x-axis at increments optimized for Nyquist sampling. During image acquisition, the excitation light provides uniform illumination of the region of interest, whereas the miniaturized sensor design significantly reduces optical scattering artefacts. The system employs acoustic tomographic reconstruction to precisely localize vascular absorbers by analysing differential time-of-flight patterns between photoacoustic sources and the sensor fibre (Fig. 1 a). The modular design of the sensor enables flexible optimization between the imaging field-of-view and detection sensitivity, adapting to specific monitoring requirements. For omnidirectional and broadband ultrasound detection, we implemented a single-polarization, single-longitudinal-mode fibre laser sensor that leverages isotropic fibre vibrations across the transverse plane (see Methods and Supplementary Information Note S1). These vibrations, characterized by inherent circular symmetry, couple efficiently with intracore light to produce measurable optical phase variations. Figure 1 b shows the omnidirectional response capability of the sensor through temporal waveforms captured from ultrasound waves delivered at various incident angles (0° to 180°), providing the extensive angular coverage needed for comprehensive tomographic imaging. The sensor's phase variations are detected through a self-delayed heterodyne mechanism implemented via a custom unbalanced fibre‒optic interferometer (Supplementary Information Note S1). This detection strategy increases the operational bandwidth to 0.3–80 MHz (Fig. 1 e), wherein the experimentally validated frequency response closely matches theoretical predictions across macroscale (0.3–1 MHz), mesoscale (1–10 MHz), and microscale (10–80 MHz) vascular imaging regimes 28 , 37 . The heterodyne approach effectively cancels common-mode noise from thermal fluctuations and environmental vibrations. Characterization of spatial resolution (Fig. 1 c) demonstrated a consistent axial resolution of approximately 50 µm throughout the 1–14 mm depth range, which is determined primarily by the sensor's detection bandwidth. The lateral resolution, governed by the central frequency and effective angular coverage, ranges from 33 µm (superficial) to 96 µm (deep) with increasing tissue depth. Notably, our system maintains sub-100 µm resolution up to a depth of 14 mm, which is critical for detailed microvascular visualization. Signal‒to-noise ratio (SNR) analysis (Fig. 1 d) revealed excellent performance, with 54 dB at a depth of 4 mm, which gradually decreased to 12 dB at 22 mm, confirming the system's suitability for deep tissue imaging. Small-animal imaging We validated the imaging capabilities of MOBILE through comprehensive vascular mapping in rodent brain and kidney models, which present significant challenges owing to their complex, multiscale vascular networks. In the brain imaging model, our system achieved detailed coronal visualization to a depth of 7 mm with near-infrared excitation light, revealing intricate vascular structures from the cortical surface to the deep thalamic regions (Fig. 2 a). The imaging encompassed not only large, deep vessels such as the posterior cerebral arteries but also captured the fine, sub-100 µm penetrating arterioles in the cerebral cortex and the hippocampal arterioles. These vessels emit extremely faint signals and are characterized by large propagation angles, making them difficult to detect with traditional compact photoacoustic imaging devices (Supplementary Note S5). The imaging accuracy was validated through comparative analysis with magnetic resonance angiography (using the Biospec 94/20 USR from Bruker), revealing consistent vascular patterns, particularly for sub-100 µm vessels in the hippocampus (Supplementary Note S5). Our system, however, demonstrated exceptional microcirculation imaging capabilities, including significantly greater angular coverage and penetration depth. This enabled comprehensive visualization of vessels in multiple orientations, rather than being limited to primarily horizontal vessels. The versatility of the system extended to rat kidney imaging, where sagittal and axial sections revealed the complete hierarchical vascular organization from the cortex to the medulla (Fig. 2 b, c). The detailed visualization included both superficial cortical vessels (e.g., the interlobular arteries) and deep medullary vessels (e.g., interlobar and segmental arteries), closely aligning with the established vascular anatomy of the kidneys 38 . The angle-encoded images (Fig. 2 d, e) demonstrate the ability of our system to detect vessels at angles exceeding 165°, significantly outperforming conventional systems, which are typically limited to sub-40° acceptance angles. Furthermore, the frequency-encoded visualization (Fig. 2 f) shows that the system is capable of effective multiscale imaging across a diameter range corresponding to one octave, wherein high-frequency components (> 30 MHz) allow detailed mapping of fine vascular structures. This comprehensive detection capability, spanning both the angular and frequency domains, makes MOBILE a powerful tool for investigating complex vascular networks across multiple tissue depths and vessel orientations. Imaging of subcutaneous vessels in humans We performed in vivo imaging of the vasculature of the human hand with MOBILE at specific monitoring sites (S1, S2) that included the finger and palm (Fig. 3 a). All measurements strictly followed ANSI safety standards for laser exposure, and ethical approval was granted by the Jinan University Ethics Committee (Approval Number: JNUKY-2023-0151, n = 9 healthy volunteers). Dual-wavelength photoacoustic imaging at 532 nm and 1064 nm revealed complementary vascular information (Fig. 3 b, c). Excitation at 532 nm, at which strong haemoglobin absorption occurs, resulted in excellent visualization of superficial structures, including capillary and the vascular plexus. Imaging at 1064 nm achieved greater penetration (~ 1 cm, shown in Fig. S10) due to reduced scattering while clearly delineating deeper vessels such as proper palmar digital arteries. Wavelength-dependent absorption enabled the assessment of tissue oxygenation through S factor analysis (the signal ratio between wavelengths). Dual-wavelength composite images (Fig. 3 d, g) revealed distinct oxygenation patterns across anatomical layers, with quantitative S factor comparisons revealing significant differences among the finger, palm, and arm regions (Fig. 3 h; additional monitoring sites are depicted in Supplementary Figure S10). These findings align with previous optical spectroscopy studies on regional variations in cutaneous circulation 39 , 40 . The omnidirectional broadband detection capability of the system enabled comprehensive vessel characterization through frequency encoding (Fig. 3 e). Vessels were classified on the basis of their acoustic signatures: high-frequency components (> 30 MHz, blue) correspond to the microvasculature, while lower-frequency components (< 30 MHz, red) represent larger vessels. This ability to image vessels at multiple scales, including arteriole (40 µm) and arteries (1.5 mm), was validated through structural analysis (Fig. 3 e inset), which demonstrated consistent vessel diameter measurements across the entire range. Depth-encoded visualization (Fig. 3 f) revealed clear stratification of vascular networks from superficial to deep tissues (0–10 mm). Correlation analysis (Fig. 3 i) revealed the relationship between vessel diameter and anatomical depth, demonstrating the ability of our system to detect vessels across multiple scales throughout the entire imaging volume while maintaining the advantages of a flexible fibre‒optic implementation. Haemodynamic response monitoring with different stimuli Venous occlusion To validate the ability of MOBILE to capture dynamic vascular responses, we performed venous occlusion-reperfusion experiments by applying pressure to the upper arm (Fig. 4 a-g). The protocol consisted of continuous monitoring of the thenar vasculature at baseline (0–60 s), during venous occlusion (60–260 s, 80 mmHg cuff pressure), and during reperfusion (260–430 s). The results provide valuable insights into endothelial function, a critical indicator of various cardiovascular risk factors 41 , 42 . Multi-depth photoacoustic imaging revealed distinct haemodynamic responses across tissue layers during the protocol (Fig. 4 b-d). The imaging results revealed a significant elevation in signal amplitude during occlusion relative to baseline, suggesting an increase in haemoglobin concentrations across all vascular layers. This phenomenon can be attributed to the obstruction of venous outflow while arterial inflow remained constant. Spatiotemporal analysis revealed depth-dependent patterns in both haemoglobin concentration (Fig. 4 e) and oxygen saturation (Fig. 4 f). The papillary dermis (PD) presented the most pronounced increase in haemoglobin (49%) and oxygen desaturation (41%) during occlusion, whereas the reticular dermis (RD) presented only moderate changes (an approximately 21% increase and 20% decrease, respectively). Interestingly, the subcutaneous tissue (ST) demonstrated relatively stable haemoglobin levels (2–3% increase) but increased oxygen saturation (13%). The observed increase in haemoglobin concentration alongside a decrease in oxygen saturation can be attributed to the restricted transport of deoxygenated blood from the peripheral vessels back to the lungs, as blood accumulates while the tissues continue to consume oxygen during occlusion. The more pronounced response of the PD relative to the RD likely reflects the greater density of capillaries in the PD, which serve as crucial exchange sites for oxygen and nutrients to epidermal cells. The relatively modest response within the ST suggests the engagement of complex oxygen redistribution mechanisms across tissue depths. Vessel-specific analysis (Fig. 4 g) revealed different responses depending on vessel type and size. The venule (V2, 87 µm) demonstrated the largest diameter changes (approximately 62%) during occlusion, peaking at approximately 180 s, whereas the arteriole (V1, 69 µm) showed similar increases in diameter (51%). Larger vessels exhibited progressively smaller changes, with the deepest arteries (V4, 826 µm) showing minimal dilation (approximately 7%), reflecting size-dependent vascular compliance. These multiparameter observations align with previous findings while reflecting the unprecedented resolution of our system for visualizing depth-specific microvascular dynamics 43 , 44 . Heat-induced hyperaemia experiment To investigate microvascular responses to thermal challenges, we performed cold-to-warm transition experiments on the palm (Fig. 4 h-n). The protocol first involved immersion of the hand in cold water (10°C), followed by gradual warming to 33°C over 590 s, allowing continuous monitoring of temperature-induced haemodynamic changes. Thermal stimulation elicited distinct vascular responses across tissue depths (Fig. 4 i-k). Unlike the pressure-induced responses, an increase in temperature primarily activates arteriovenous shunts, resulting in depth-specific haemodynamic patterns. The PD showed moderate changes (haemoglobin concentration: +17%, oxygen saturation: -16%), whereas deeper layers presented more pronounced responses. Both the RD and ST demonstrated substantial increases in the haemoglobin concentration (RD: +42%, ST: +34%) and oxygen saturation (RD: +21%, ST: +26%), reflecting the activation of deeper arteriovenous shunts that facilitate direct blood flow return without tissue oxygen exchange (Fig. 4 l, m). Vessel-specific analysis (Fig. 4 n) revealed a similar pattern of dilation in vessels of different calibres. Unlike venous occlusion stimulation, the vascular changes induced by water temperature were not significantly dependent on the type of blood vessel. Instead, a similar degree of dilation was observed across various types of blood vessels, with the venule (V5, 78 µm) and arteriole (V6, 184 µm) dilating by 53% and 35%, respectively. Larger vessels (V7: 407 µm, V8: 485 µm) also exhibited considerable diameter increases (≥ 42%), demonstrating that across the vessel hierarchy, the thermal sensitivity differed but showed similar trends. This phenomenon occurs because changes in water temperature primarily influence the metabolic activities of vascular smooth muscle cells and neural regulatory mechanisms. These changes lead to the relaxation of vascular smooth muscle, resulting in vasodilation. Since this mechanism is ubiquitous across different types of blood vessels, the corresponding degree of vessel dilation is relatively consistent 45 . Continuous monitoring of the microcirculation during exercise Exercise induces complex adaptations in the circulatory system, extending beyond well-documented systemic changes in heart rate and blood pressure to intricate microvascular responses. While these microcirculatory adaptations are crucial for exercise performance and tissue homeostasis, the real-time dynamics remain poorly understood, primarily owing to technical limitations in continuous monitoring during active motion. Here, we demonstrate the ability of our MOBILE system to reveal previously unobservable microcirculatory dynamics during two distinct exercise protocols. Vessel-specific microcirculatory adaptation during free motion To investigate microvascular responses during unrestricted movement, we implemented a comprehensive monitoring protocol integrating a handheld MOBILE probe by the right hand with concurrent physiological measurements (Fig. 5 a). The experimental setup combined dual-wavelength (1064/532 nm) photoacoustic imaging while simultaneously recording transcutaneous oxygen partial pressure (TCM4, Radiometer, sensor electrodes attached to the palm of the left hand and heart rate dynamics with a sports watch (GT3, Huawei). Volunteers (n = 3) abstained from exercise and use of stimulants for 30 minutes before imaging. The protocol consisted of three phases, as shown in the photoacoustic images: a baseline period (Fig. 5 b, t = 80 s), a period of exercises that included squats (Fig. 5 c, t = 560 s), and a postexercise recovery period (Fig. 5 d, t = 920 s). Depth-resolved imaging revealed distinct layer-specific responses in both PA amplitude (Fig. 5 e) and oxygen saturation (Fig. 5 f): during the exercise process, the superficial PD exhibited a 6% increase in haemoglobin concentration coupled with a 4% increase in oxygenation, whereas the RD showed a similar pattern, with elevated oxyhaemoglobin levels despite only a 2% increase in vessel concentration. Notably, the ST layer demonstrated decreased oxygenation, which is consistent with exercise-induced arterial vasoconstriction. The system's superior spatial resolution allowed unprecedented vessel-specific analysis during active motion (Fig. 5 g). We observed different responses among vessel types: the venule (V1, 77 µm) exhibited significant dilation (24% increase in diameter), while the arteriole (V2, 88 µm) showed marked constriction (14% reduction); V3 (290 µm) and V4 (281 µm) arteries demonstrated consistent constriction patterns (10% and 16%, respectively). These vessel-specific adaptations were temporally associated with systemic physiological changes, as evidenced by a concurrent elevation in heart rate and partial pressure of oxygen (pO₂) dynamics from the sports watch and transcutaneous oxygen partial pressure TCM4 (Fig. 5 h). This heterogeneous response pattern, which is undetectable with conventional monitoring methods, provides direct evidence of the mechanisms underlying exercise-induced blood flow redistribution. High-intensity exercise reveals complex microcirculation dynamics To extend our investigation to more demanding conditions, we developed a probe integrated with a handlebar for high-intensity cycling exercise (Fig. 5 i). The protocol included a 280 s baseline period (0 to 280 s), an 840 s cycling period (280 to 1120 s), and a 600 s recovery period (1120 to 1720 s). The integrated probe design ensured stable contact during vigorous motion, whereas the ultrasound coupling gel maintained consistent imaging conditions despite the presence of exercise-induced movement. Photoacoustic imaging revealed distinct vascular patterns across the exercise phases (Fig. 5 j-l), with the baseline state (t = 40 s) showing a normal vessel distribution, the exercise period (t = 880 s) demonstrating significant vascular adaptation, and the recovery phase (t = 1600 s) exhibiting a gradual return to the patterns observed at baseline. High-intensity exercise elicited more pronounced microcirculatory adaptations than free motion did, with temporal analysis revealing that the peak heart rate corresponded with decreased rather than increased skin blood concentration, indicating greater blood redistribution. Depth-resolved analysis (Fig. 5 m, n) demonstrated layer-specific responses: during the exercise process, the PD showed a rapid decrease in oxygenation (27%) with a simultaneous reduction in the haemoglobin concentration (7%). The RD exhibited subtle increases in both oxygenation (3%) and blood concentration (4%), suggesting minimal involvement in the oxygen exchange processes. The ST displayed a distinctive pattern of decreased oxygenation (25%) coupled with increased haemoglobin concentration (14%), which is consistent with exercise-induced arterial constriction. Unlike transcutaneous oximetry, which provides only single-point, indirect measurements of tissue oxygenation, our photoacoustic system enables simultaneous monitoring of blood concentration and oxygenation across multiple tissue layers with high spatial and temporal resolution. The advantages of this system are evidenced by the results of our vessel-specific analysis (Fig. 5 o, p), which revealed different vascular adaptations during high-intensity exercise: the arteriole (V6, 86 µm) demonstrated up to 19% constriction, whereas the venule (V5, 83 µm) showed 32% dilation, and vessels (V7, 268 µm; V8, 740 µm) exhibited consistent constriction patterns (20% and 8%, respectively). These detailed microvascular dynamics, combined with layer-specific haemodynamic changes, significantly exceeded the sensitivity of transcutaneous measurements (7% decrease in pO 2 ). The temporal correlation between vascular responses and heart rate dynamics captured rapid blood oxygen fluctuations during exercise transitions, which were particularly pronounced during heart rate elevation phases, followed by quick stabilization during steady-state exercise. These dynamic patterns, typically undetectable with conventional technologies, provide unprecedented insights into exercise-induced vascular adaptation mechanisms. Discussion and conclusion In summary, we have developed MOBILE, an innovative photoacoustic system that enables visualization of the evolution of the microcirculation in depth and at high spatiotemporal resolutions. By integrating photoacoustic imaging with miniaturized, wideband, omnidirectional optical ultrasound sensors, MOBILE transcends conventional portable microcirculation monitoring devices in both ability and versatility. The system achieves remarkable imaging performance with sub-100 µm resolution up to a depth of 10 mm while maintaining the ability to visualize vessels across multiple scales (40 µm to 1.5 mm in diameter) within the dermal and subcutaneous layers. Through extensive validation across various physiological conditions and physical activities, we have demonstrated the robust performance and adaptability of the system to diverse clinical scenarios, making it particularly promising for use in intensive care units (ICUs) and intraoperative monitoring. Developments in microcirculatory imaging technologies reflect a persistent challenge in balancing portability, resolution, and imaging depth. Conventional ultrasound imaging, while capable of centimetre-level penetration, lacks the molecular specificity essential for comprehensive vascular assessments. Purely optical methods offer valuable functional information such as the amount of blood oxygenation but are fundamentally limited in their ability to visualize greater penetration depth owing to light scattering. Photoacoustic imaging has emerged as a promising solution, combining light excitation with acoustic detection to allow high-resolution molecular imaging at greater depths without the need for contrast agents. While station-based photoacoustic systems, which utilize large-sized annular arrays or high-numerical-aperture detectors, have demonstrated significant potential in diagnosing metabolic diseases and cancers, their bulky configuration prevents continuous monitoring during physical activity. Recent attempts at miniaturization, particularly in the form of patch-based devices, have shown promising as portable solutions, but are constrained by the inherent limitations of electrical sensors, namely, a relatively low bandwidth and reception angle upon miniaturization, resulting in compromised imaging performance with respect to their station-based counterparts. MOBILE overcomes these limitations through its optic ultrasound sensor, which is 300 times smaller than conventional piezoelectric transducers while maintaining exceptional detection capabilities. The sensor achieves omnidirectional ultrasound detection over an ultrawide bandwidth (0.3–80 MHz) and remarkable sensitivity, delivering a consistent axial resolution of approximately 50 µm across multiple skin layers. These breakthroughs in sensor design have fundamentally transformed photoacoustic probe construction, resulting in unprecedented flexibility in geometric configurations while maintaining station-level imaging performance. Our experimental results regarding exercise-induced responses demonstrate the system's ability to capture complex microvascular adaptations, including vessel-specific vasoconstriction patterns and depth-resolved changes in oxygen metabolism. These dynamic vascular responses share remarkable similarities with the microcirculatory alterations observed in critical conditions such as shock, where heterogeneous vessel responses and oxygen use patterns play crucial roles in tissue perfusion. In critical care settings, the system could serve as a novel approach for the early identification of microcirculatory dysfunction through the real-time monitoring of vessel-specific responses. In exercise physiology research, the system could provide direct data for analysing the hierarchical regulation of tissue perfusion during physical activity. Furthermore, in disease monitoring, the system could enable characterization of pathological changes in microvascular function from early to advanced disease stages, with the multiparameter assessment capability of the system potentially advancing microcirculatory pathophysiology research and optimizing related clinical interventions. Despite these advances, several challenges remain before our system can be implemented in clinical practice. First, current imaging speed limitations and the presence of motion artefacts require sophisticated compensation algorithms, potentially addressable through large-scale multiplexed sensor arrays for improved parallel detection. Second, while our dual-wavelength approach (532 nm and 1064 nm) is cost-effective, expanding the wavelength range could allow monitoring of diverse, additional biomolecules, including melanin, lipids, glucose, proteins, and exogenous contrast agents. Third, further miniaturization towards patch-based configurations, leveraging the inherent flexibility of optical fibres in parallel acquisition systems, could improve the tomographic imaging speed while maintaining the lightweight characteristics of the system. These advancements would pave the way for sophisticated endoscopic, handheld, and wearable applications, potentially revolutionizing point-of-care diagnostics and continuous patient monitoring. Methods Fibre-optic ultrasound sensor The sensor was constructed on the basis of a single-frequency, single-polarization fibre laser built in an active, rare-earth-doped optical fibre (EY-305, Coractive, Inc.) with dual wavelength-matched Bragg gratings. The laser architecture features two precisely engineered 3-mm Bragg reflectors that provide optical feedback, created with a phase mask (period: 1062.2 nm, Ibsen Photonics) under controlled UV exposure from an excimer laser (Coherent, Compex Pro 110F, 40 mJ, 30 Hz). This configuration generates a highly polarization-selective resonant spectrum. When pumped by a custom-designed 980-nm low-noise semiconductor laser, the cavity maintains single-polarized laser operation. Ultrasound-induced perturbations modulate the laser frequency, which is detected through a self-delayed heterodyne detection scheme (detailed in the Supplementary Note S1). Sensor calibration and characterization We performed a frequency response calibration of the fibre sensor using photoacoustic signals. The ultrasonic source was generated by a 532 nm pulsed laser (Pulse width: 2 ns) inducing the PDMS-carbon powder composite layer coated on the end face of the optical fibre. We conducted ultrasonic pressure calibration using a calibrated needle hydrophone (NH0200, Precision Acoustics). Initial sound pressure calibration measurements were obtained 1 mm from the ultrasonic source using the hydrophone, with systematic optimization of the transmitting and receiving angles. The ultrasonic amplitude spectrum density H ( Ω ) was analysed in conjunction with the hydrophone's known responsivity ( S H ( Ω ), 48 mV/MPa over 40 MHz) to determine the pressure spectral density P ( Ω ) = H ( Ω )/ S H ( Ω ). Next, we assessed the acoustic response of the fibre sensor by positioning it orthogonally to the incident ultrasound waves and recorded the acoustically induced laser phase variations. The sensor was rotated in 30° increments to record these data shown in Fig. 1 b. Finally, its sensitivity was received shown in Fig. 1 e. MOBILE imaging system configuration For photoacoustic excitation, we utilized a Q-switched Nd:YAG laser (Dawa-200, Beamtech) with dual wavelengths of 532 and 1064 nm, a pulse width of 8 ns and a repetition rate of 20 Hz. The initial spot size of the laser beam was 6 mm, which we expanded to a 2.5 cm-diameter illumination spot with a beam diffuser (DG10-120, Thorlabs). The optical fluence at 532 nm was maintained at 6.5 mJ/cm², significantly below the American National Standards Institute (ANSI) safety limit of 20 mJ/cm². Similarly, the fluence at 1064 nm was maintained at 12.9 mJ/cm², also well under the ANSI threshold of 100 mJ/cm². Sensor array for dynamic imaging We developed an 8-element fibre optic sensor array utilizing wavelength and time division multiplexing for enhanced imaging speed in dynamic microvascular imaging. The array elements operate at eight distinct wavelengths (1542.12–1547.72 nm, 0.8 nm interval) corresponding to standard DWDM communication channels. The multiplexed optical signals undergo uniform amplification through a customized erbium-doped fibre amplifier to achieve consistent channel power levels (~ 23 dBm). The amplified signals are processed through a self-coherent interference pathway and systematically transmitted to the photodetectors for photoelectric conversion. Finally, these electrical signals were simultaneously collected by an 8-channel data acquisition card and demodulated into PA signals, resulting in an imaging speed of 5 seconds per frame. Performance characterization of MOBILE Spatial resolution : Black-dyed microspheres (10 µm diameter) were employed to assess the spatial resolution of the system. The sample preparation protocol consisted of the following: First, a dissolved agar solution was poured into a mould and allowed to solidify. A centrifuged microsphere suspension was subsequently carefully deposited onto the solidified agar substrate. A final agar layer was then overlaid to immobilize the microspheres, creating a three-layer agar block with microspheres embedded in the central plane. In this way, we ensured a uniform planar distribution of the microspheres, allowing calibration of the resolution across multiple depths. Following microsphere imaging acquisition, we analysed the particles at depths ranging from 2 mm to 15 mm relative to the surface of the fibre-optic sensor surface. Lateral and axial resolution metrics were obtained through envelope detection of the point-spread functions, and the resulting depth-dependent resolution profile is presented in Fig. 1 c. Image depth : The penetration capacity of the photoacoustic system was evaluated using pencil graphite arrays embedded within chicken breast tissue. A 3D-printed chamber was used to stably accommodate the chicken breast to a depth of 30 mm and enable precise parallel insertion of eight 0.5 mm-diameter pieces of pencil graphite at 3 mm vertical intervals. Depth-dependent signal‒to-noise ratio (SNR) metrics, as shown in Fig. 1 d, were derived from reconstructed photoacoustic images of the pieces of pencil lead, in which the noise amplitudes were quantified from the root mean square (r.m.s.) of the background noise and the signal amplitudes were determined by the peak photoacoustic intensities of the reconstructions of the pencil graphite. Image reconstruction and processing We implemented a dual speed-of-sound (SoS) back-projection algorithm using the MATLAB k-wave toolbox for image reconstruction, which significantly reduced imaging artefacts and improved visualization of perpendicular vessels (detailed in Supplementary Figure S4). The spatiotemporal analysis of the vascular dynamics was conduced on the basis of the dual-wavelength (1064/532 nm) photoacoustic signals, wherein vessel width measurements were obtained with the full width at half maximum (FWHM) of the normalized envelope curves following Gaussian fitting. To improve the visualizations, we employed frequency-encoded and angular-encoded processing pipelines, incorporating Hessian-based Frangi vesselness filters for contrast enhancement. The final dual-wavelength-merged images were produced through sequential processing, including straightening, optical compensation, and colour-coded fusion (detailed processing protocols are provided in Supplementary Note S2). Animal imaging protocol We used 10-week-old male BALB/c mice weighing 30 g for brain imaging. Before imaging, each mouse was positioned on a temperature-controlled cushion and anaesthetized with 1.5% vaporized isoflurane. Pharmaceutical-grade ophthalmic ointment was applied to cover the eyes of the mice. We subsequently removed the hair on the head using clippers and depilatory cream, followed by opening the scalp and removing the skull using a handheld drill. The mouse was then secured on a mouse stand to immobilize the head and minimize movement during photoacoustic imaging. We use 7-week-old male SD rats weighing 250 g for kidney imaging. The rats were first anaesthetized with 1.5% vaporized isoflurane, placed supine on a temperature-controlled cushion, and dissected after shaving. A 30-mm skin incision was made along the midline from 15 mm below the sternum towards the genitals. A piece of gauze was placed over the drape and attached lightly to the muscle layer with haemostat forceps on each side of the incision to allow access to the kidney. The left kidney was chosen for dissection, as the right kidney is adjacent to the liver and portal vein, which can be easily injured during dissection. All procedures were conducted in “Guiding Principles in the Care and Use of Animals” (GB/T 35892 − 2018, China) and were approved by the Laboratory Animal Ethics Committee of Guangzhou Huateng Biomedical Technology (IACUC: C202312-10). Subcutaneous vessel imaging protocol The human imaging experiments were conducted in accordance with a protocol approved by the Ethics Committee of Jinan University (Approval Number: JNUKY-2023-0151, n = 9 healthy volunteers). Total nine healthy adult male and female volunteers, all aged 24 years, participated in the study. Written informed consent was obtained from each participant in accordance with the approved protocol. To ensure safety from laser exposure, all participants were equipped with safety glasses throughout the experiment. The participants were seated comfortably with their arms extended and positioned at heart level in a room maintained at standard temperature. For imaging of human subcutaneous vessels using dual-wavelength illumination, the system was applied to the fingers, palms, and arms of the volunteers. Prior to imaging, ultrasound gel was applied to improve image quality. The participants were then asked to position the targeted imaging area beneath the imaging apparatus. Protocol for the dynamic monitoring of microcirculatory responses For haemodynamic monitoring in response to cuff occlusion, a blood pressure cuff was secured around the right upper arm of each participant and inflated to 80 mmHg to induce venous occlusion while maintaining normal blood pressure conditions. The region of interest for these experiments was the thenar area of the palm. Baseline images were taken at rest before initiating a 200 s period of venous occlusion. Immediately after imaging, the cuff pressure was quickly released. This was followed by a 170 s resting phase, allowing time for the blood vessels to return to their normal state before proceeding with further vascular imaging. For the heat-induced hyperaemia response experiment, the palms of the volunteers were placed in a water tank containing a hole in the top, with the region of interest for imaging maintained in direct contact with the water surface and aligned perpendicular to the fibre-optic sensor. The water temperature was initially set to 10°C and subsequently increased to 33°C over a period of 590 s through controlled heating. Throughout this imaging protocol, the volunteers were asked to keep their palms as stable as possible to ensure consistent skin contact with the water surface and minimize motion artefacts during data acquisition. Free motion/cycling monitoring The handheld circumferential scanning probe primarily consists of three parts: a probe shell, the probe core assembly, and a drive motor (See in Supplementary Figure S12). The probe core represents the critical functional module, integrating three precision-engineered elements: fibre optic bundle apertures for light transmission, mirror slots containing reflective optical elements, and an optical fibre sensor unit mounted on a motor-driven rotational bracket. The excitation light emitted from the fibre bundle is primarily reflected at the mirror interface before illuminating the target imaging area. The optical fibre sensor component, rigidly affixed to the rotating bracket coupled to the motor shaft, achieves circumferential scanning through controlled rotational displacement. For low-intensity free motion, continuous photoacoustic imaging monitoring was achieved by having the volunteers directly grasp the imaging probe shell and align the palm target imaging area with the excitation light irradiation zone. During the entire imaging monitoring process, the volunteer's palm maintained close contact with the imaging probe shell to reduce artefacts caused by shaking during movement. To enable real-time monitoring during cycling motion, the conventional handlebar grip of an exercise bicycle was systematically redesigned. The cylindrical section of the probe shell was ergonomically substituted for the original handle grip structure. Through precise mechanical integration, the probe core assembly was embedded within the handlebar-style shell, thereby achieving seamless sensor integration with the cycling apparatus. This structural modification preserves the full rotational freedom of the handlebar while maintaining continuous optical coupling during dynamic motion. Declarations Conflict of interest The authors declare no competing interests. Author contributions Y. Liang, L. Jin, X. Bai and B. Guan conceived the project and supervised the research. W. Li, X. Bai, P. He, C. Wu, C. Song, S. Li, Y. Zheng, Z. Hu, Z. Zhang prepared the sample and performed the experiments. W. Li, X. Bai, Y. Liang, and L. Jin contributed to data analysis. Y. Liang, L. Jin, and L. Cheng performed theoretical analysis. Q. Zhang and X. Zhong provide the technical support of experiments. W. Li, Y. Liang. and Y.C. Zhang processed reconstructed images. Y. Liang, L. Jin and X. Bai prepared the manuscript writing. B. Guan participated in the discussion of manuscript writing and supported the funding. Acknowledgements This work was supported by the Natural Science Foundation of China (62322506, 62275104, 62135006, 62122031, 62205125), National Key Technologies R&D Program of China (2023YFF0715302), China Postdoctoral Science Foundation (2025M770849), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2019BT02X105), and the Guangzhou Science and Technology Program (2024B03J1288, 2024B03J0254). Data availability The data that support the findings of this study are available from the authors upon reasonable request. Code availability The authors declare that for data collection the commercially available software from LabVIEW 2015 (National Instruments, USA) and Matlab 2021a (Matlab, Mathworks, USA) were used. Data analysis was conducted in Matlab using its built-in functions. The image algorithm has been patented and is available upon discretion from the corresponding author. References Tuma RF, Durán WN, Ley K (2011) Microcirculation. Academic Ellis CG, Jagger J, Sharpe M (2005) The microcirculation as a functional system. Crit Care 9:S3 Den Uil CA et al (2008) The Microcirculation in Health and Critical Disease. Prog Cardiovasc Dis 51:161–170 Popel AS, Johnson PC (2005) Microcirculation and hemorheology. Annu Rev Fluid Mech 37:43–69 Secomb TW (2017) Blood Flow in the Microcirculation. 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Nat Commun 13:7757 Karlas A et al (2023) Dermal features derived from optoacoustic tomograms via machine learning correlate microangiopathy phenotypes with diabetes stage. Nat Biomed Eng 7:1667–1682 Kok NFM et al (2008) Complex Vascular Anatomy in Live Kidney Donation: Imaging and Consequences for Clinical Outcome. Transplantation 85:1760–1765 Thorn CE, Matcher SJ, Meglinski IV, Shore AC (2009) Is mean blood saturation a useful marker of tissue oxygenation? Am J Physiol-Heart C 296:H1289–H1295 Schwarz M, Buehler A, Aguirre J, Ntziachristos V (2016) Three-dimensional multispectral optoacoustic mesoscopy reveals melanin and blood oxygenation in human skin in vivo. J Biophotonics 9:55–60 Wilkinson IB, Webb DJ (2001) Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications. Br J Clin Pharmacol 52:631–646 Haage P, Krings T, Schmitz-Rode T (2002) Nontraumatic vascular emergencies: imaging and intervention in acute venous occlusion. 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Supplementary Files SupplementaryInformationfinal20250717.docx Supplementary Information VenousOcclusionfinal.mp4 Venous Occlusion Video HeatInducedfinal.mp4 Heat Induced Video CyclingExercisefinal.mp4 Cycling Exercise Video FreeMotionfinal.mp4 Free Motion Video Cite Share Download PDF Status: Published Journal Publication published 08 Jan, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7154196","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":504168743,"identity":"17fde8de-bda6-40ba-ac2d-a42a34b07227","order_by":0,"name":"Yizhi 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1","display":"","copyAsset":false,"role":"figure","size":86545,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMOBILE system architecture and performance characterization.\u003c/strong\u003e (a) Schematic illustration of the MOBILE platform, featuring an ultracompact fibre-optic sensor for microvascular imaging. The system employs a single-scan tomographic reconstruction approach, wherein photoacoustic signals with distinct time-of-flight patterns from multiple vascular absorbers are processed to generate high-resolution images. (b) The omnidirectional detection capability of the system is demonstrated through temporal waveforms recorded at different incident angles (0°-180°), highlighting the isotropic response characteristics of the sensor. (c) Depth-dependent spatial resolution analysis shows the lateral and axial resolution profiles of the system, revealing its sub -100 μm resolution capabilities throughout the imaging range. (d) Signal-to-noise ratio (SNR) characterization across various imaging depths. (e) Experimentally validated frequency response spectrum (0.3–80 MHz) compared with theoretical predictions. These data indicate that the system is capable of imaging vessels at multiple scales, from macroscale (\u0026gt;1 mm) to microscale (\u0026lt;100 μm), through a single sensor.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/91b309b4a72f6221c67c6132.png"},{"id":89990161,"identity":"d53bbf9e-ed82-410f-ac35-56ed2505dfae","added_by":"auto","created_at":"2025-08-27 07:10:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":270382,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComprehensive vascular visualization in the rodent brain and kidney using MOBILE.\u003c/strong\u003e (a) Mouse brain vasculature in the coronal plane, revealing key structures, including the cortical penetrating arteriole (CPA), dorsal thalamic artery (DTA), transverse collicular artery (TCA), hippocampal arteriole (HA), thalamoperforating artery (THA) and posterior cerebral artery (PCA). (b, c) Rat kidney vasculature in the sagittal and axial planes, demonstrating hierarchical organization from the interlobular arteriole (ILLA) to the segmental artery (SA), with clear visualization of the interlobar artery (ILA) and arcuate artery (AA) across the cortical and medullary regions. (d, e) Angle-encoded vascular maps (0°-180°) highlight the omnidirectional detection capability of the system. In these maps, vessel orientation is colour-coded relative to the horizontal plane. (f) Frequency-encoded image reveals vessel-size distributions, with higher frequencies (blue) corresponding to smaller vessel diameters. Scale bar: 1 mm.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/5cbcc105331fad1644fd940c.png"},{"id":89990166,"identity":"b6a06496-0230-4833-b6f4-0842402a5fdc","added_by":"auto","created_at":"2025-08-27 07:10:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":802755,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMicrovascular photoacoustic imaging of the human hand.\u003c/strong\u003e (a) Schematic illustration of monitoring locations (S1, S2) in the finger and palm. (b) 532 nm photoacoustic image of finger vasculature (S1), revealing superficial microvascular structures, including distinct capillary loops and the dermal vascular plexus. (c) 1064 nm imaging demonstrating greater penetration depth, visualizing deeper vascular structures, including the distal branch and proper palmar digital artery. (d) Dual-wavelength, surfaced-flattened image of the finger region (S1), where the relative S factor distribution reveals changes in tissue oxygenation across different anatomical layers, including the epidermis (EP), papillary dermis (PD), reticular dermis (RD), and subcutaneous tissue (ST). (e) Frequency-encoded palm vasculature with red and blue colours representing vessels detected at \u0026lt;30 MHz and 30~80 MHz frequencies, respectively, with the inset showing resolved vessel diameters ranging from 40 µm (arteriole) to 1.5 mm (arteries). (f) Depth-encoded visualization demonstrating penetration depths up to 10 mm in the tissue of the palm. (g) Dual-wavelength composite imaging of the palm across the 30 mm lateral range, with S factor mapping revealing the spatial distribution of tissue oxygenation. (h) Quantitative comparison of S-factors across the finger, palm and arm regions measured in the papillary dermis layer (*p \u0026lt; 0.05). (i) Correlation analysis between vessel diameter and imaging depth, demonstrating the ability of the system to visualize vessels at multiple scales. Scale bar: 1 mm for main.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/90098cc766a06fa007868b61.png"},{"id":89990113,"identity":"b601e08b-c505-4fc3-915c-06bad63910c5","added_by":"auto","created_at":"2025-08-27 07:10:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":281922,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDynamic monitoring of microcirculatory responses under venous occlusion and thermal stimulation.\u003c/strong\u003e (a) Experimental setup for venous occlusion challenge using a blood pressure cuff (80 mmHg). (b-d) Representative photoacoustic images acquired at baseline (t = 20 s), during occlusion (t = 180 s), and after pressure release (t = 360 s), showing vessel morphology changes (V1-V4) across different tissue depths. (e) Depth-resolved photoacoustic amplitude changes reflecting haemoglobin concentration changes across the papillary dermis (PD), reticular dermis (RD), and subcutaneous tissue (ST) at baseline (Bas., 0–60 s), during occlusion (Occ., 60–260 s), and after pressure release (Rel., 260–430 s) phases. (f) Corresponding S factor changes indicating tissue oxygenation dynamics throughout the protocol. (g) Quantitative analysis of vessel diameter fractional changes for vessels of different calibres (V1: 69 μm, V2: 87 μm, V3: 299 μm, V4: 826 μm). (h) Schematic illustration of the thermal stimulation setup. (i-k) Photoacoustic images acquired during cold water immersion (10°C, t = 20 s), heating (t = 250 s) and warming (33°C, t = 550 s). (l) Depth-resolved photoacoustic amplitude changes during temperature transitions. (m) Corresponding S-factor changes showing the oxygenation response to thermal stimulation. (n) Vessel diameter changes for different-diameter vessels (V5: 78 μm, V6: 184 μm, V7: 407 μm, V8: 485 μm) during the cold-to-warm transition. Scale bars: 1 mm.\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/9f38576314e31133a4db15f9.png"},{"id":89990253,"identity":"e20eab57-573a-4a6c-b411-6e570e16c20b","added_by":"auto","created_at":"2025-08-27 07:10:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":278643,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eContinuous monitoring of exercise-induced microcirculatory dynamics using the MOBILE system. \u003c/strong\u003e(a-h) Low-intensity free motion monitoring and (i-p) high-intensity cycling exercise monitoring. Experimental schematics showing the system configurations: (a) Imaging probe with a sports watch and blood gas analyser patch for free motion and (i) probe integration into a spinning-bike handlebar. (b-d) Photoacoustic images with oxygen saturation mapping during the free motion protocol at baseline (t=80 s), during squatting exercise (t=560 s), and during recovery (t=920 s). (j-l) Similar acquisitions were made during the cycling protocol at baseline (t=40 s), during cycling (t=880 s), and during recovery (t=1600 s). Colour-coded spatiotemporal analysis showing (e, m) photoacoustic amplitude changes and (f, n) oxygen saturation changes across tissue depths (PD: papillary dermis, RD: reticular dermis, ST: subcutaneous tissue). Quantitative analysis of vessel diameter changes for vessels V1-V8 during (g) free motion and (o) the cycling exercise. Concurrent physiological measurements of heart rate, transcutaneous pO₂ and sO\u003csub\u003e2\u003c/sub\u003e of PD layer during the (h) free motion and (p) cycling protocols. The light blue shaded regions in (g, h, o, p) indicate periods of exercise. Free motion protocol timeline: baseline (0–200 s), squat (200–600 s), and recovery (600–1000 s). Cycling protocol timeline: baseline (0–280 s), cycling (280–1120 s), and recovery (1120–1720 s). Scale bars: 1 mm.\u003c/p\u003e","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/15fb034f11c86dfe68c644a2.png"},{"id":102284772,"identity":"a10a9b3c-18a6-4b54-823d-18c58c565496","added_by":"auto","created_at":"2026-02-10 08:07:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2912777,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/1a16342b-08de-4774-a5f5-2bbd011fc69f.pdf"},{"id":89990112,"identity":"599fffb4-2e82-4653-a09f-b7144b73f803","added_by":"auto","created_at":"2025-08-27 07:10:03","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10506408,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"SupplementaryInformationfinal20250717.docx","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/10122cd38176e74a3aadd909.docx"},{"id":89990114,"identity":"b8e79ab7-5c6d-4995-a6fa-2e088c47f2c4","added_by":"auto","created_at":"2025-08-27 07:10:03","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":13960856,"visible":true,"origin":"","legend":"Venous Occlusion Video","description":"","filename":"VenousOcclusionfinal.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/4ed2a437c090cceaf01f6e65.mp4"},{"id":89990180,"identity":"30bd5721-02b2-43b9-b68b-64bc7f052a34","added_by":"auto","created_at":"2025-08-27 07:10:10","extension":"mp4","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":17858382,"visible":true,"origin":"","legend":"Heat Induced Video","description":"","filename":"HeatInducedfinal.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/3769528adb4710f2a07f43a8.mp4"},{"id":89990212,"identity":"90f867b9-bc8a-44df-a14c-c244493126be","added_by":"auto","created_at":"2025-08-27 07:10:13","extension":"mp4","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":17584407,"visible":true,"origin":"","legend":"Cycling Exercise Video","description":"","filename":"CyclingExercisefinal.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/e9805a5ba54a944f65526fd8.mp4"},{"id":89990243,"identity":"55291e49-08f1-43a1-afd4-f2904917a434","added_by":"auto","created_at":"2025-08-27 07:10:16","extension":"mp4","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":68012668,"visible":true,"origin":"","legend":"Free Motion Video","description":"","filename":"FreeMotionfinal.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7154196/v1/7831ee6c605bdbf2e0beed78.mp4"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Dynamic Microvascular Monitoring with MOBILE: Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe microcirculation, an intricate network of small blood vessels, serves as an important conduit for maintaining tissue functionality and metabolic activities through the dynamic regulation of the local blood supply \u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Understanding the dynamics of the microcirculation during natural physiological activities is crucial, as the most significant microcirculatory adaptations occur in response to exercise, postural changes, and environmental stimuli. Moreover, microcirculatory dysfunction is increasingly recognized as an early indicator of multiple pathological conditions, including cardiovascular diseases, sepsis, and diabetes; therefore, continuous assessment of microcirculatory dynamics could aid in both early diagnosis and therapeutic monitoring \u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. However, comprehensive assessment of these dynamics remains technically challenging, as it simultaneously requires high spatiotemporal resolution, adequate imaging depth, and continuous monitoring capabilities during unrestricted movement. Current imaging technologies are unable to meet all these requirements: conventional modalities such as CT and MRI, while offering whole-body scanning capabilities, are impractical for continuous monitoring because of operational constraints; microbubble contrast agent-based ultrasound allows only intermittent visualization \u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e–\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e; and optical approaches, including video microscopy \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and optical coherence tomography \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, are fundamentally limited in terms of either penetration depth or spatial resolution.\u003c/p\u003e\u003cp\u003ePhotoacoustic imaging has emerged as a promising approach to address these challenges by combining optical excitation with ultrasonic detection, allowing high-resolution visualization of vascular structures at clinically relevant depths \u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e–\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. While conventional photoacoustic systems have demonstrated effectiveness in analysing haemodynamics \u003csup\u003e\u003cspan additionalcitationids=\"CR25 CR26 CR27\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e–\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e and characterizing the microcirculation under various pathological conditions \u003csup\u003e\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e–\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e, their reliance on bulky ultrasound transducer arrays has limited applications primarily to stationary diagnostic imaging tasks, such as breast cancer detection \u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Recent developments in small \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e, wearable photoacoustic devices \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e represent progress towards dynamic monitoring, but current systems can only visualize a few isolated vessels, which is unsuitable for achieving a comprehensive assessment of the microvasculature.\u003c/p\u003e\u003cp\u003eIn this study, we introduce MOBILE (Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities), a novel approach for imaging the microcirculation that employs a miniaturized photoacoustic probe based on a compact fibre-optic ultrasound sensor. Our sensor leverages isotropic vibrations within an optical fibre to achieve omnidirectional, broadband (0.3–80 MHz) ultrasound detection and exceptional sensitivity. Through these technical advancements, MOBILE allows visualization of vessels spanning multiple scales (40 µm to 1.5 mm diameter) within the dermis and subcutaneous tissues up to a depth of 1 cm with high resolution. The compact sensor design—including a sensing area 300-times smaller than that of conventional piezoelectric transducers—facilitates versatile implementation in both handheld and wearable formats while maintaining high performance across a wide range of angles. We demonstrate the clinical utility of MOBILE through comprehensive monitoring of the peripheral microcirculation during various physiological challenges, revealing vessel-specific dynamics in terms of haemoglobin concentration, diameter, and oxygen saturation across the vascular tree. Notably, our system allows the simultaneous characterization of distinct responses across vessel sizes and depths, from superficial capillaries to deep subcutaneous vessels, providing novel insights into the heterogeneous behaviour of the microcirculation during natural physiological activities. The results of this study bridge a critical gap in our understanding of vessel-resolved microcirculatory dynamics and their role in systemic haemodynamic regulation.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eMOBILE system design and performance characterization\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents our MOBILE system for dynamic microvascular imaging. The miniaturized design is based on a fibre-optic ultrasound sensor positioned horizontally along the z-axis, with linear or curvilinear scanning performed along the x-axis at increments optimized for Nyquist sampling. During image acquisition, the excitation light provides uniform illumination of the region of interest, whereas the miniaturized sensor design significantly reduces optical scattering artefacts. The system employs acoustic tomographic reconstruction to precisely localize vascular absorbers by analysing differential time-of-flight patterns between photoacoustic sources and the sensor fibre (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). The modular design of the sensor enables flexible optimization between the imaging field-of-view and detection sensitivity, adapting to specific monitoring requirements.\u003c/p\u003e\u003cp\u003eFor omnidirectional and broadband ultrasound detection, we implemented a single-polarization, single-longitudinal-mode fibre laser sensor that leverages isotropic fibre vibrations across the transverse plane (see Methods and Supplementary Information Note S1). These vibrations, characterized by inherent circular symmetry, couple efficiently with intracore light to produce measurable optical phase variations. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb shows the omnidirectional response capability of the sensor through temporal waveforms captured from ultrasound waves delivered at various incident angles (0° to 180°), providing the extensive angular coverage needed for comprehensive tomographic imaging. The sensor's phase variations are detected through a self-delayed heterodyne mechanism implemented via a custom unbalanced fibre‒optic interferometer (Supplementary Information Note S1). This detection strategy increases the operational bandwidth to 0.3–80 MHz (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee), wherein the experimentally validated frequency response closely matches theoretical predictions across macroscale (0.3–1 MHz), mesoscale (1–10 MHz), and microscale (10–80 MHz) vascular imaging regimes \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. The heterodyne approach effectively cancels common-mode noise from thermal fluctuations and environmental vibrations. Characterization of spatial resolution (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec) demonstrated a consistent axial resolution of approximately 50 µm throughout the 1–14 mm depth range, which is determined primarily by the sensor's detection bandwidth. The lateral resolution, governed by the central frequency and effective angular coverage, ranges from 33 µm (superficial) to 96 µm (deep) with increasing tissue depth. Notably, our system maintains sub-100 µm resolution up to a depth of 14 mm, which is critical for detailed microvascular visualization. Signal‒to-noise ratio (SNR) analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed) revealed excellent performance, with 54 dB at a depth of 4 mm, which gradually decreased to 12 dB at 22 mm, confirming the system's suitability for deep tissue imaging.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSmall-animal imaging\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe validated the imaging capabilities of MOBILE through comprehensive vascular mapping in rodent brain and kidney models, which present significant challenges owing to their complex, multiscale vascular networks. In the brain imaging model, our system achieved detailed coronal visualization to a depth of 7 mm with near-infrared excitation light, revealing intricate vascular structures from the cortical surface to the deep thalamic regions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). The imaging encompassed not only large, deep vessels such as the posterior cerebral arteries but also captured the fine, sub-100 µm penetrating arterioles in the cerebral cortex and the hippocampal arterioles. These vessels emit extremely faint signals and are characterized by large propagation angles, making them difficult to detect with traditional compact photoacoustic imaging devices (Supplementary Note S5). The imaging accuracy was validated through comparative analysis with magnetic resonance angiography (using the Biospec 94/20 USR from Bruker), revealing consistent vascular patterns, particularly for sub-100 µm vessels in the hippocampus (Supplementary Note S5). Our system, however, demonstrated exceptional microcirculation imaging capabilities, including significantly greater angular coverage and penetration depth. This enabled comprehensive visualization of vessels in multiple orientations, rather than being limited to primarily horizontal vessels. The versatility of the system extended to rat kidney imaging, where sagittal and axial sections revealed the complete hierarchical vascular organization from the cortex to the medulla (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, c). The detailed visualization included both superficial cortical vessels (e.g., the interlobular arteries) and deep medullary vessels (e.g., interlobar and segmental arteries), closely aligning with the established vascular anatomy of the kidneys \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe angle-encoded images (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed, e) demonstrate the ability of our system to detect vessels at angles exceeding 165°, significantly outperforming conventional systems, which are typically limited to sub-40° acceptance angles. Furthermore, the frequency-encoded visualization (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ef) shows that the system is capable of effective multiscale imaging across a diameter range corresponding to one octave, wherein high-frequency components (\u0026gt; 30 MHz) allow detailed mapping of fine vascular structures. This comprehensive detection capability, spanning both the angular and frequency domains, makes MOBILE a powerful tool for investigating complex vascular networks across multiple tissue depths and vessel orientations.\u003c/p\u003e\u003cp\u003e\u003cb\u003eImaging of subcutaneous vessels in humans\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe performed in vivo imaging of the vasculature of the human hand with MOBILE at specific monitoring sites (S1, S2) that included the finger and palm (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). All measurements strictly followed ANSI safety standards for laser exposure, and ethical approval was granted by the Jinan University Ethics Committee (Approval Number: JNUKY-2023-0151, n = 9 healthy volunteers). Dual-wavelength photoacoustic imaging at 532 nm and 1064 nm revealed complementary vascular information (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb, c). Excitation at 532 nm, at which strong haemoglobin absorption occurs, resulted in excellent visualization of superficial structures, including capillary and the vascular plexus. Imaging at 1064 nm achieved greater penetration (~ 1 cm, shown in Fig. S10) due to reduced scattering while clearly delineating deeper vessels such as proper palmar digital arteries. Wavelength-dependent absorption enabled the assessment of tissue oxygenation through S factor analysis (the signal ratio between wavelengths). Dual-wavelength composite images (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed, g) revealed distinct oxygenation patterns across anatomical layers, with quantitative S factor comparisons revealing significant differences among the finger, palm, and arm regions (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eh; additional monitoring sites are depicted in Supplementary Figure S10). These findings align with previous optical spectroscopy studies on regional variations in cutaneous circulation \u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe omnidirectional broadband detection capability of the system enabled comprehensive vessel characterization through frequency encoding (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee). Vessels were classified on the basis of their acoustic signatures: high-frequency components (\u0026gt; 30 MHz, blue) correspond to the microvasculature, while lower-frequency components (\u0026lt; 30 MHz, red) represent larger vessels. This ability to image vessels at multiple scales, including arteriole (40 µm) and arteries (1.5 mm), was validated through structural analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee inset), which demonstrated consistent vessel diameter measurements across the entire range. Depth-encoded visualization (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef) revealed clear stratification of vascular networks from superficial to deep tissues (0–10 mm). Correlation analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ei) revealed the relationship between vessel diameter and anatomical depth, demonstrating the ability of our system to detect vessels across multiple scales throughout the entire imaging volume while maintaining the advantages of a flexible fibre‒optic implementation.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eHaemodynamic response monitoring with different stimuli\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eVenous occlusion\u003c/em\u003e\u003c/p\u003e\u003cp\u003eTo validate the ability of MOBILE to capture dynamic vascular responses, we performed venous occlusion-reperfusion experiments by applying pressure to the upper arm (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea-g). The protocol consisted of continuous monitoring of the thenar vasculature at baseline (0–60 s), during venous occlusion (60–260 s, 80 mmHg cuff pressure), and during reperfusion (260–430 s). The results provide valuable insights into endothelial function, a critical indicator of various cardiovascular risk factors \u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e\u003cp\u003eMulti-depth photoacoustic imaging revealed distinct haemodynamic responses across tissue layers during the protocol (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb-d). The imaging results revealed a significant elevation in signal amplitude during occlusion relative to baseline, suggesting an increase in haemoglobin concentrations across all vascular layers. This phenomenon can be attributed to the obstruction of venous outflow while arterial inflow remained constant. Spatiotemporal analysis revealed depth-dependent patterns in both haemoglobin concentration (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee) and oxygen saturation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef). The papillary dermis (PD) presented the most pronounced increase in haemoglobin (49%) and oxygen desaturation (41%) during occlusion, whereas the reticular dermis (RD) presented only moderate changes (an approximately 21% increase and 20% decrease, respectively). Interestingly, the subcutaneous tissue (ST) demonstrated relatively stable haemoglobin levels (2–3% increase) but increased oxygen saturation (13%). The observed increase in haemoglobin concentration alongside a decrease in oxygen saturation can be attributed to the restricted transport of deoxygenated blood from the peripheral vessels back to the lungs, as blood accumulates while the tissues continue to consume oxygen during occlusion. The more pronounced response of the PD relative to the RD likely reflects the greater density of capillaries in the PD, which serve as crucial exchange sites for oxygen and nutrients to epidermal cells. The relatively modest response within the ST suggests the engagement of complex oxygen redistribution mechanisms across tissue depths.\u003c/p\u003e\u003cp\u003eVessel-specific analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eg) revealed different responses depending on vessel type and size. The venule (V2, 87 µm) demonstrated the largest diameter changes (approximately 62%) during occlusion, peaking at approximately 180 s, whereas the arteriole (V1, 69 µm) showed similar increases in diameter (51%). Larger vessels exhibited progressively smaller changes, with the deepest arteries (V4, 826 µm) showing minimal dilation (approximately 7%), reflecting size-dependent vascular compliance. These multiparameter observations align with previous findings while reflecting the unprecedented resolution of our system for visualizing depth-specific microvascular dynamics \u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eHeat-induced hyperaemia experiment\u003c/em\u003e\u003c/p\u003e\u003cp\u003eTo investigate microvascular responses to thermal challenges, we performed cold-to-warm transition experiments on the palm (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eh-n). The protocol first involved immersion of the hand in cold water (10°C), followed by gradual warming to 33°C over 590 s, allowing continuous monitoring of temperature-induced haemodynamic changes. Thermal stimulation elicited distinct vascular responses across tissue depths (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ei-k). Unlike the pressure-induced responses, an increase in temperature primarily activates arteriovenous shunts, resulting in depth-specific haemodynamic patterns. The PD showed moderate changes (haemoglobin concentration: +17%, oxygen saturation: -16%), whereas deeper layers presented more pronounced responses. Both the RD and ST demonstrated substantial increases in the haemoglobin concentration (RD: +42%, ST: +34%) and oxygen saturation (RD: +21%, ST: +26%), reflecting the activation of deeper arteriovenous shunts that facilitate direct blood flow return without tissue oxygen exchange (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003el, m).\u003c/p\u003e\u003cp\u003eVessel-specific analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003en) revealed a similar pattern of dilation in vessels of different calibres. Unlike venous occlusion stimulation, the vascular changes induced by water temperature were not significantly dependent on the type of blood vessel. Instead, a similar degree of dilation was observed across various types of blood vessels, with the venule (V5, 78 µm) and arteriole (V6, 184 µm) dilating by 53% and 35%, respectively. Larger vessels (V7: 407 µm, V8: 485 µm) also exhibited considerable diameter increases (≥ 42%), demonstrating that across the vessel hierarchy, the thermal sensitivity differed but showed similar trends. This phenomenon occurs because changes in water temperature primarily influence the metabolic activities of vascular smooth muscle cells and neural regulatory mechanisms. These changes lead to the relaxation of vascular smooth muscle, resulting in vasodilation. Since this mechanism is ubiquitous across different types of blood vessels, the corresponding degree of vessel dilation is relatively consistent \u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eContinuous monitoring of the microcirculation during exercise\u003c/b\u003e\u003c/p\u003e\u003cp\u003eExercise induces complex adaptations in the circulatory system, extending beyond well-documented systemic changes in heart rate and blood pressure to intricate microvascular responses. While these microcirculatory adaptations are crucial for exercise performance and tissue homeostasis, the real-time dynamics remain poorly understood, primarily owing to technical limitations in continuous monitoring during active motion. Here, we demonstrate the ability of our MOBILE system to reveal previously unobservable microcirculatory dynamics during two distinct exercise protocols.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eVessel-specific microcirculatory adaptation during free motion\u003c/em\u003e\u003c/p\u003e\u003cp\u003eTo investigate microvascular responses during unrestricted movement, we implemented a comprehensive monitoring protocol integrating a handheld MOBILE probe by the right hand with concurrent physiological measurements (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea). The experimental setup combined dual-wavelength (1064/532 nm) photoacoustic imaging while simultaneously recording transcutaneous oxygen partial pressure (TCM4, Radiometer, sensor electrodes attached to the palm of the left hand and heart rate dynamics with a sports watch (GT3, Huawei). Volunteers (n = 3) abstained from exercise and use of stimulants for 30 minutes before imaging. The protocol consisted of three phases, as shown in the photoacoustic images: a baseline period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb, t = 80 s), a period of exercises that included squats (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec, t = 560 s), and a postexercise recovery period (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed, t = 920 s).\u003c/p\u003e\u003cp\u003eDepth-resolved imaging revealed distinct layer-specific responses in both PA amplitude (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee) and oxygen saturation (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef): during the exercise process, the superficial PD exhibited a 6% increase in haemoglobin concentration coupled with a 4% increase in oxygenation, whereas the RD showed a similar pattern, with elevated oxyhaemoglobin levels despite only a 2% increase in vessel concentration. Notably, the ST layer demonstrated decreased oxygenation, which is consistent with exercise-induced arterial vasoconstriction.\u003c/p\u003e\u003cp\u003eThe system's superior spatial resolution allowed unprecedented vessel-specific analysis during active motion (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eg). We observed different responses among vessel types: the venule (V1, 77 µm) exhibited significant dilation (24% increase in diameter), while the arteriole (V2, 88 µm) showed marked constriction (14% reduction); V3 (290 µm) and V4 (281 µm) arteries demonstrated consistent constriction patterns (10% and 16%, respectively). These vessel-specific adaptations were temporally associated with systemic physiological changes, as evidenced by a concurrent elevation in heart rate and partial pressure of oxygen (pO₂) dynamics from the sports watch and transcutaneous oxygen partial pressure TCM4 (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh). This heterogeneous response pattern, which is undetectable with conventional monitoring methods, provides direct evidence of the mechanisms underlying exercise-induced blood flow redistribution.\u003c/p\u003e\u003cp\u003e\u003cem\u003eHigh-intensity exercise reveals complex microcirculation dynamics\u003c/em\u003e\u003c/p\u003e\u003cp\u003eTo extend our investigation to more demanding conditions, we developed a probe integrated with a handlebar for high-intensity cycling exercise (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ei). The protocol included a 280 s baseline period (0 to 280 s), an 840 s cycling period (280 to 1120 s), and a 600 s recovery period (1120 to 1720 s). The integrated probe design ensured stable contact during vigorous motion, whereas the ultrasound coupling gel maintained consistent imaging conditions despite the presence of exercise-induced movement. Photoacoustic imaging revealed distinct vascular patterns across the exercise phases (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ej-l), with the baseline state (t = 40 s) showing a normal vessel distribution, the exercise period (t = 880 s) demonstrating significant vascular adaptation, and the recovery phase (t = 1600 s) exhibiting a gradual return to the patterns observed at baseline. High-intensity exercise elicited more pronounced microcirculatory adaptations than free motion did, with temporal analysis revealing that the peak heart rate corresponded with decreased rather than increased skin blood concentration, indicating greater blood redistribution.\u003c/p\u003e\u003cp\u003eDepth-resolved analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003em, n) demonstrated layer-specific responses: during the exercise process, the PD showed a rapid decrease in oxygenation (27%) with a simultaneous reduction in the haemoglobin concentration (7%). The RD exhibited subtle increases in both oxygenation (3%) and blood concentration (4%), suggesting minimal involvement in the oxygen exchange processes. The ST displayed a distinctive pattern of decreased oxygenation (25%) coupled with increased haemoglobin concentration (14%), which is consistent with exercise-induced arterial constriction.\u003c/p\u003e\u003cp\u003eUnlike transcutaneous oximetry, which provides only single-point, indirect measurements of tissue oxygenation, our photoacoustic system enables simultaneous monitoring of blood concentration and oxygenation across multiple tissue layers with high spatial and temporal resolution. The advantages of this system are evidenced by the results of our vessel-specific analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eo, p), which revealed different vascular adaptations during high-intensity exercise: the arteriole (V6, 86 µm) demonstrated up to 19% constriction, whereas the venule (V5, 83 µm) showed 32% dilation, and vessels (V7, 268 µm; V8, 740 µm) exhibited consistent constriction patterns (20% and 8%, respectively). These detailed microvascular dynamics, combined with layer-specific haemodynamic changes, significantly exceeded the sensitivity of transcutaneous measurements (7% decrease in pO\u003csub\u003e2\u003c/sub\u003e). The temporal correlation between vascular responses and heart rate dynamics captured rapid blood oxygen fluctuations during exercise transitions, which were particularly pronounced during heart rate elevation phases, followed by quick stabilization during steady-state exercise. These dynamic patterns, typically undetectable with conventional technologies, provide unprecedented insights into exercise-induced vascular adaptation mechanisms.\u003c/p\u003e"},{"header":"Discussion and conclusion","content":"\u003cp\u003eIn summary, we have developed MOBILE, an innovative photoacoustic system that enables visualization of the evolution of the microcirculation in depth and at high spatiotemporal resolutions. By integrating photoacoustic imaging with miniaturized, wideband, omnidirectional optical ultrasound sensors, MOBILE transcends conventional portable microcirculation monitoring devices in both ability and versatility. The system achieves remarkable imaging performance with sub-100 µm resolution up to a depth of 10 mm while maintaining the ability to visualize vessels across multiple scales (40 µm to 1.5 mm in diameter) within the dermal and subcutaneous layers. Through extensive validation across various physiological conditions and physical activities, we have demonstrated the robust performance and adaptability of the system to diverse clinical scenarios, making it particularly promising for use in intensive care units (ICUs) and intraoperative monitoring.\u003c/p\u003e\u003cp\u003eDevelopments in microcirculatory imaging technologies reflect a persistent challenge in balancing portability, resolution, and imaging depth. Conventional ultrasound imaging, while capable of centimetre-level penetration, lacks the molecular specificity essential for comprehensive vascular assessments. Purely optical methods offer valuable functional information such as the amount of blood oxygenation but are fundamentally limited in their ability to visualize greater penetration depth owing to light scattering. Photoacoustic imaging has emerged as a promising solution, combining light excitation with acoustic detection to allow high-resolution molecular imaging at greater depths without the need for contrast agents. While station-based photoacoustic systems, which utilize large-sized annular arrays or high-numerical-aperture detectors, have demonstrated significant potential in diagnosing metabolic diseases and cancers, their bulky configuration prevents continuous monitoring during physical activity. Recent attempts at miniaturization, particularly in the form of patch-based devices, have shown promising as portable solutions, but are constrained by the inherent limitations of electrical sensors, namely, a relatively low bandwidth and reception angle upon miniaturization, resulting in compromised imaging performance with respect to their station-based counterparts. MOBILE overcomes these limitations through its optic ultrasound sensor, which is 300 times smaller than conventional piezoelectric transducers while maintaining exceptional detection capabilities. The sensor achieves omnidirectional ultrasound detection over an ultrawide bandwidth (0.3–80 MHz) and remarkable sensitivity, delivering a consistent axial resolution of approximately 50 µm across multiple skin layers. These breakthroughs in sensor design have fundamentally transformed photoacoustic probe construction, resulting in unprecedented flexibility in geometric configurations while maintaining station-level imaging performance.\u003c/p\u003e\u003cp\u003eOur experimental results regarding exercise-induced responses demonstrate the system's ability to capture complex microvascular adaptations, including vessel-specific vasoconstriction patterns and depth-resolved changes in oxygen metabolism. These dynamic vascular responses share remarkable similarities with the microcirculatory alterations observed in critical conditions such as shock, where heterogeneous vessel responses and oxygen use patterns play crucial roles in tissue perfusion. In critical care settings, the system could serve as a novel approach for the early identification of microcirculatory dysfunction through the real-time monitoring of vessel-specific responses. In exercise physiology research, the system could provide direct data for analysing the hierarchical regulation of tissue perfusion during physical activity. Furthermore, in disease monitoring, the system could enable characterization of pathological changes in microvascular function from early to advanced disease stages, with the multiparameter assessment capability of the system potentially advancing microcirculatory pathophysiology research and optimizing related clinical interventions.\u003c/p\u003e\u003cp\u003eDespite these advances, several challenges remain before our system can be implemented in clinical practice. First, current imaging speed limitations and the presence of motion artefacts require sophisticated compensation algorithms, potentially addressable through large-scale multiplexed sensor arrays for improved parallel detection. Second, while our dual-wavelength approach (532 nm and 1064 nm) is cost-effective, expanding the wavelength range could allow monitoring of diverse, additional biomolecules, including melanin, lipids, glucose, proteins, and exogenous contrast agents. Third, further miniaturization towards patch-based configurations, leveraging the inherent flexibility of optical fibres in parallel acquisition systems, could improve the tomographic imaging speed while maintaining the lightweight characteristics of the system. These advancements would pave the way for sophisticated endoscopic, handheld, and wearable applications, potentially revolutionizing point-of-care diagnostics and continuous patient monitoring.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eFibre-optic ultrasound sensor\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe sensor was constructed on the basis of a single-frequency, single-polarization fibre laser built in an active, rare-earth-doped optical fibre (EY-305, Coractive, Inc.) with dual wavelength-matched Bragg gratings. The laser architecture features two precisely engineered 3-mm Bragg reflectors that provide optical feedback, created with a phase mask (period: 1062.2 nm, Ibsen Photonics) under controlled UV exposure from an excimer laser (Coherent, Compex Pro 110F, 40 mJ, 30 Hz). This configuration generates a highly polarization-selective resonant spectrum. When pumped by a custom-designed 980-nm low-noise semiconductor laser, the cavity maintains single-polarized laser operation. Ultrasound-induced perturbations modulate the laser frequency, which is detected through a self-delayed heterodyne detection scheme (detailed in the Supplementary Note S1).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSensor calibration and characterization\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe performed a frequency response calibration of the fibre sensor using photoacoustic signals. The ultrasonic source was generated by a 532 nm pulsed laser (Pulse width: 2 ns) inducing the PDMS-carbon powder composite layer coated on the end face of the optical fibre. We conducted ultrasonic pressure calibration using a calibrated needle hydrophone (NH0200, Precision Acoustics). Initial sound pressure calibration measurements were obtained 1 mm from the ultrasonic source using the hydrophone, with systematic optimization of the transmitting and receiving angles. The ultrasonic amplitude spectrum density \u003cem\u003eH\u003c/em\u003e(\u003cem\u003eΩ\u003c/em\u003e) was analysed in conjunction with the hydrophone's known responsivity (\u003cem\u003eS\u003c/em\u003e\u003csub\u003eH\u003c/sub\u003e(\u003cem\u003eΩ\u003c/em\u003e), 48 mV/MPa over 40 MHz) to determine the pressure spectral density \u003cem\u003eP\u003c/em\u003e(\u003cem\u003eΩ\u003c/em\u003e) = \u003cem\u003eH\u003c/em\u003e(\u003cem\u003eΩ\u003c/em\u003e)/\u003cem\u003eS\u003c/em\u003e\u003csub\u003eH\u003c/sub\u003e(\u003cem\u003eΩ\u003c/em\u003e). Next, we assessed the acoustic response of the fibre sensor by positioning it orthogonally to the incident ultrasound waves and recorded the acoustically induced laser phase variations. The sensor was rotated in 30° increments to record these data shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb. Finally, its sensitivity was received shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ee.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMOBILE imaging system configuration\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFor photoacoustic excitation, we utilized a Q-switched Nd:YAG laser (Dawa-200, Beamtech) with dual wavelengths of 532 and 1064 nm, a pulse width of 8 ns and a repetition rate of 20 Hz. The initial spot size of the laser beam was 6 mm, which we expanded to a 2.5 cm-diameter illumination spot with a beam diffuser (DG10-120, Thorlabs). The optical fluence at 532 nm was maintained at 6.5 mJ/cm², significantly below the American National Standards Institute (ANSI) safety limit of 20 mJ/cm². Similarly, the fluence at 1064 nm was maintained at 12.9 mJ/cm², also well under the ANSI threshold of 100 mJ/cm².\u003c/p\u003e\u003cp\u003e\u003cb\u003eSensor array for dynamic imaging\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe developed an 8-element fibre optic sensor array utilizing wavelength and time division multiplexing for enhanced imaging speed in dynamic microvascular imaging. The array elements operate at eight distinct wavelengths (1542.12–1547.72 nm, 0.8 nm interval) corresponding to standard DWDM communication channels. The multiplexed optical signals undergo uniform amplification through a customized erbium-doped fibre amplifier to achieve consistent channel power levels (~ 23 dBm). The amplified signals are processed through a self-coherent interference pathway and systematically transmitted to the photodetectors for photoelectric conversion. Finally, these electrical signals were simultaneously collected by an 8-channel data acquisition card and demodulated into PA signals, resulting in an imaging speed of 5 seconds per frame.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePerformance characterization of MOBILE\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSpatial resolution\u003c/span\u003e: Black-dyed microspheres (10 µm diameter) were employed to assess the spatial resolution of the system. The sample preparation protocol consisted of the following: First, a dissolved agar solution was poured into a mould and allowed to solidify. A centrifuged microsphere suspension was subsequently carefully deposited onto the solidified agar substrate. A final agar layer was then overlaid to immobilize the microspheres, creating a three-layer agar block with microspheres embedded in the central plane. In this way, we ensured a uniform planar distribution of the microspheres, allowing calibration of the resolution across multiple depths. Following microsphere imaging acquisition, we analysed the particles at depths ranging from 2 mm to 15 mm relative to the surface of the fibre-optic sensor surface. Lateral and axial resolution metrics were obtained through envelope detection of the point-spread functions, and the resulting depth-dependent resolution profile is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec.\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eImage depth\u003c/span\u003e: The penetration capacity of the photoacoustic system was evaluated using pencil graphite arrays embedded within chicken breast tissue. A 3D-printed chamber was used to stably accommodate the chicken breast to a depth of 30 mm and enable precise parallel insertion of eight 0.5 mm-diameter pieces of pencil graphite at 3 mm vertical intervals. Depth-dependent signal‒to-noise ratio (SNR) metrics, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed, were derived from reconstructed photoacoustic images of the pieces of pencil lead, in which the noise amplitudes were quantified from the root mean square (r.m.s.) of the background noise and the signal amplitudes were determined by the peak photoacoustic intensities of the reconstructions of the pencil graphite.\u003c/p\u003e\u003cp\u003e\u003cb\u003eImage reconstruction and processing\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe implemented a dual speed-of-sound (SoS) back-projection algorithm using the MATLAB k-wave toolbox for image reconstruction, which significantly reduced imaging artefacts and improved visualization of perpendicular vessels (detailed in Supplementary Figure S4). The spatiotemporal analysis of the vascular dynamics was conduced on the basis of the dual-wavelength (1064/532 nm) photoacoustic signals, wherein vessel width measurements were obtained with the full width at half maximum (FWHM) of the normalized envelope curves following Gaussian fitting. To improve the visualizations, we employed frequency-encoded and angular-encoded processing pipelines, incorporating Hessian-based Frangi vesselness filters for contrast enhancement. The final dual-wavelength-merged images were produced through sequential processing, including straightening, optical compensation, and colour-coded fusion (detailed processing protocols are provided in Supplementary Note S2).\u003c/p\u003e\u003cp\u003e\u003cb\u003eAnimal imaging protocol\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe used 10-week-old male BALB/c mice weighing 30 g for brain imaging. Before imaging, each mouse was positioned on a temperature-controlled cushion and anaesthetized with 1.5% vaporized isoflurane. Pharmaceutical-grade ophthalmic ointment was applied to cover the eyes of the mice. We subsequently removed the hair on the head using clippers and depilatory cream, followed by opening the scalp and removing the skull using a handheld drill. The mouse was then secured on a mouse stand to immobilize the head and minimize movement during photoacoustic imaging.\u003c/p\u003e\u003cp\u003eWe use 7-week-old male SD rats weighing 250 g for kidney imaging. The rats were first anaesthetized with 1.5% vaporized isoflurane, placed supine on a temperature-controlled cushion, and dissected after shaving. A 30-mm skin incision was made along the midline from 15 mm below the sternum towards the genitals. A piece of gauze was placed over the drape and attached lightly to the muscle layer with haemostat forceps on each side of the incision to allow access to the kidney. The left kidney was chosen for dissection, as the right kidney is adjacent to the liver and portal vein, which can be easily injured during dissection. All procedures were conducted in “Guiding Principles in the Care and Use of Animals” (GB/T 35892 − 2018, China) and were approved by the Laboratory Animal Ethics Committee of Guangzhou Huateng Biomedical Technology (IACUC: C202312-10).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSubcutaneous vessel imaging protocol\u003c/b\u003e\u003c/p\u003e\u003cp\u003e The human imaging experiments were conducted in accordance with a protocol approved by the Ethics Committee of Jinan University (Approval Number: JNUKY-2023-0151, n = 9 healthy volunteers). Total nine healthy adult male and female volunteers, all aged 24 years, participated in the study. Written informed consent was obtained from each participant in accordance with the approved protocol. To ensure safety from laser exposure, all participants were equipped with safety glasses throughout the experiment. The participants were seated comfortably with their arms extended and positioned at heart level in a room maintained at standard temperature. For imaging of human subcutaneous vessels using dual-wavelength illumination, the system was applied to the fingers, palms, and arms of the volunteers. Prior to imaging, ultrasound gel was applied to improve image quality. The participants were then asked to position the targeted imaging area beneath the imaging apparatus.\u003c/p\u003e\u003cp\u003e\u003cb\u003eProtocol for the dynamic monitoring of microcirculatory responses\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFor haemodynamic monitoring in response to cuff occlusion, a blood pressure cuff was secured around the right upper arm of each participant and inflated to 80 mmHg to induce venous occlusion while maintaining normal blood pressure conditions. The region of interest for these experiments was the thenar area of the palm. Baseline images were taken at rest before initiating a 200 s period of venous occlusion. Immediately after imaging, the cuff pressure was quickly released. This was followed by a 170 s resting phase, allowing time for the blood vessels to return to their normal state before proceeding with further vascular imaging.\u003c/p\u003e\u003cp\u003eFor the heat-induced hyperaemia response experiment, the palms of the volunteers were placed in a water tank containing a hole in the top, with the region of interest for imaging maintained in direct contact with the water surface and aligned perpendicular to the fibre-optic sensor. The water temperature was initially set to 10°C and subsequently increased to 33°C over a period of 590 s through controlled heating. Throughout this imaging protocol, the volunteers were asked to keep their palms as stable as possible to ensure consistent skin contact with the water surface and minimize motion artefacts during data acquisition.\u003c/p\u003e\u003cp\u003e\u003cb\u003eFree motion/cycling monitoring\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe handheld circumferential scanning probe primarily consists of three parts: a probe shell, the probe core assembly, and a drive motor (See in Supplementary Figure S12). The probe core represents the critical functional module, integrating three precision-engineered elements: fibre optic bundle apertures for light transmission, mirror slots containing reflective optical elements, and an optical fibre sensor unit mounted on a motor-driven rotational bracket. The excitation light emitted from the fibre bundle is primarily reflected at the mirror interface before illuminating the target imaging area. The optical fibre sensor component, rigidly affixed to the rotating bracket coupled to the motor shaft, achieves circumferential scanning through controlled rotational displacement.\u003c/p\u003e\u003cp\u003eFor low-intensity free motion, continuous photoacoustic imaging monitoring was achieved by having the volunteers directly grasp the imaging probe shell and align the palm target imaging area with the excitation light irradiation zone. During the entire imaging monitoring process, the volunteer's palm maintained close contact with the imaging probe shell to reduce artefacts caused by shaking during movement.\u003c/p\u003e\u003cp\u003eTo enable real-time monitoring during cycling motion, the conventional handlebar grip of an exercise bicycle was systematically redesigned. The cylindrical section of the probe shell was ergonomically substituted for the original handle grip structure. Through precise mechanical integration, the probe core assembly was embedded within the handlebar-style shell, thereby achieving seamless sensor integration with the cycling apparatus. This structural modification preserves the full rotational freedom of the handlebar while maintaining continuous optical coupling during dynamic motion.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of interest\u003c/h2\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e\u003cp\u003eY. Liang, L. Jin, X. Bai and B. Guan conceived the project and supervised the research. W. Li, X. Bai, P. He, C. Wu, C. Song, S. Li, Y. Zheng, Z. Hu, Z. Zhang prepared the sample and performed the experiments. W. Li, X. Bai, Y. Liang, and L. Jin contributed to data analysis. Y. Liang, L. Jin, and L. Cheng performed theoretical analysis. Q. Zhang and X. Zhong provide the technical support of experiments. W. Li, Y. Liang. and Y.C. Zhang processed reconstructed images. Y. Liang, L. Jin and X. Bai prepared the manuscript writing. B. Guan participated in the discussion of manuscript writing and supported the funding.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eThis work was supported by the Natural Science Foundation of China (62322506, 62275104, 62135006, 62122031, 62205125), National Key Technologies R\u0026amp;D Program of China (2023YFF0715302), China Postdoctoral Science Foundation (2025M770849), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2019BT02X105), and the Guangzhou Science and Technology Program (2024B03J1288, 2024B03J0254).\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the authors upon reasonable request.\u003c/p\u003e\u003ch2\u003eCode availability\u003c/h2\u003e\u003cp\u003eThe authors declare that for data collection the commercially available software from LabVIEW 2015 (National Instruments, USA) and Matlab 2021a (Matlab, Mathworks, USA) were used. Data analysis was conducted in Matlab using its built-in functions. The image algorithm has been patented and is available upon discretion from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTuma RF, Dur\u0026aacute;n WN, Ley K (2011) Microcirculation. Academic\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEllis CG, Jagger J, Sharpe M (2005) The microcirculation as a functional system. Crit Care 9:S3\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDen Uil CA et al (2008) The Microcirculation in Health and Critical Disease. Prog Cardiovasc Dis 51:161\u0026ndash;170\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePopel AS, Johnson PC (2005) Microcirculation and hemorheology. Annu Rev Fluid Mech 37:43\u0026ndash;69\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSecomb TW (2017) Blood Flow in the Microcirculation. 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SPIE\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhong X et al (2024) Free-moving-state microscopic imaging of cerebral oxygenation and hemodynamics with a photoacoustic fiberscope. Light Sci Appl 13:5\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTian C et al (2024) Image reconstruction from photoacoustic projections. Photonics Insights 3:R06\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim J et al (2024) 3D Multiparametric Photoacoustic Computed Tomography of Primary and Metastatic Tumors in Living Mice. ACS Nano 18:18176\u0026ndash;18190\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen Y et al (2024) Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain. 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J Biophotonics 11:e201700359\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7154196/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7154196/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMicrocirculation monitoring is crucial for evaluating cardiovascular health and detecting organ dysfunction early, but existing bedside imaging techniques often cannot provide sufficient resolution and depth for dynamic assessment during natural physiological activities. Here, we present MOBILE (Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities), a novel photoacoustic imaging system that allows unrestricted microcirculatory monitoring with 40 \u0026micro;m resolution and penetration depth of 1 cm, allowing stratified visualization of dynamic vascular responses. This platform features an ultracompact fibre-optic sensor capable of omnidirectional ultrasound-based detection across a large bandwidth (0.3\u0026ndash;80 MHz). The compact design of the system facilitates point-of-care monitoring through seamless integration with portable devices or existing clinical systems. Through a comprehensive evaluation of the patient\u0026rsquo;s haemodynamic parameters, MOBILE reveals distinct dynamic responses of vessels at different tissue depths, from superficial microvessels to deep subcutaneous vessels, capturing vessel-specific changes in diameter, haemoglobin concentration, and tissue oxygenation during numerous physiological challenges. This platform offers new possibilities for understanding microcirculatory responses and improving critical care management through high-resolution vessel monitoring.\u003c/p\u003e","manuscriptTitle":"Dynamic Microvascular Monitoring with MOBILE: Miniaturized Omnidirectional Broadband Photoacoustic Imaging System for Living Entities","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 07:09:40","doi":"10.21203/rs.3.rs-7154196/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"afe40070-89e3-4994-8d98-22b493ce556c","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":53566827,"name":"Biological sciences/Biological techniques/Imaging/Optical imaging"},{"id":53566828,"name":"Physical sciences/Optics and photonics/Optical techniques/Imaging and sensing"}],"tags":[],"updatedAt":"2026-02-10T08:06:51+00:00","versionOfRecord":{"articleIdentity":"rs-7154196","link":"https://doi.org/10.1038/s41467-025-68190-6","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2026-01-08 05:00:00","publishedOnDateReadable":"January 8th, 2026"},"versionCreatedAt":"2025-08-27 07:09:40","video":"","vorDoi":"10.1038/s41467-025-68190-6","vorDoiUrl":"https://doi.org/10.1038/s41467-025-68190-6","workflowStages":[]},"version":"v1","identity":"rs-7154196","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7154196","identity":"rs-7154196","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}