Abstract
Current intravascular multimodality imaging systems are constrained by imaging speed, catheter size, and system stability, limiting their practical use in dynamic or vessel assessments. Although significant progress has been made in multimodality intravascular imaging, most existing implementations typically operate at rotational speeds in the low-hertz range (approximately 1–15 Hz), which restricts both clinical translation and biologically relevant investigation. Here, we present a next-generation multimodality intravascular imaging system implemented in a 3-French catheter that achieves high-speed rotational imaging at 30 Hz, representing a 2-fold increase in rotational imaging speed compared to typical multimodality intravascular implementations, while maintaining stable, co-registered IVUS and IVPA imaging. This increase in imaging speed enables reliable visualization of lipid-rich plaques over extended vascular segments with reduced motion artifacts, facilitating more consistent assessment of plaque distribution under cardiac-induced vascular motion. Instead of introducing a new imaging mechanism, this study demonstrates how system-level optimization can enable more robust investigation of plaque development and progression in biologically relevant intravascular environments.
1. Introduction
Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation within the arterial wall and remains a leading cause of cardiovascular morbidity and mortality worldwide. Lipid-rich plaques, particularly those associated with foam cell formation and necrotic core development, are closely linked to plaque vulnerability and adverse cardiovascular events [1,2]. Accurate assessment of both plaque morphology and composition is therefore essential for understanding plaque development and progression and for improving intravascular diagnostic strategies [3–8]. Intravascular imaging techniques have been developed to directly visualize vascular pathology in situ [9–11]. Intravascular ultrasound (IVUS) enables real-time assessment of vessel morphology and plaque burden, while intravascular photoacoustic imaging (IVPA) provides compositional contrast based on optical absorption, with strong sensitivity to lipid at wavelengths around 1.7 µm [12,13]. As no single imaging modality can fully characterize complex atherosclerotic lesions, multimodality intravascular imaging approaches combining IVUS and IVPA have been proposed to simultaneously capture complementary structural and compositional information [14–16].
Despite significant progress in multimodality intravascular imaging, practical implementation under dynamic vascular conditions remains challenging. Most reported IVUS/IVPA systems operate at relatively low rotational imaging speeds, typically in the low-hertz range, due to limitations in laser repetition rate, signal detection sensitivity, catheter mechanics, and overall system stability [17]. Insufficient imaging speed leads to motion artifacts, limited longitudinal coverage during pullback, and reduced robustness when imaging dynamically moving intravascular environments [18]. These constraints restrict both biologically relevant investigation of plaque heterogeneity and the translational potential of multimodality intravascular imaging.
Rather than introducing a new imaging mechanism, this work focuses on system-level optimization to overcome longstanding limitations in imaging speed and signal stability in multimodality intravascular imaging. To this end, a compact hybrid IVUS–IVPA imaging system was developed with targeted design choices aimed at improving robustness under high-speed operation. In particular, a common-mode choke was incorporated into the signal reception pathway as a system-level strategy to suppress electromagnetic interference and reduce noise coupling [19]. While commonly used in electronic systems to mitigate conducted noise, its implementation in this miniaturized intravascular imaging platform plays a critical role in stabilizing signal acquisition during high-speed rotational imaging. By integrating a high-repetition-rate 1.7 µm laser source, an optimized ultrasound detection pathway, and a 3-French catheter design, the proposed system enables stable, co-registered IVUS and IVPA imaging at rotational speeds of 30 Hz. This capability represents a substantial increase in practical imaging speed compared to typical multimodality intravascular implementations and advances the usability of intravascular multimodality imaging under biologically relevant conditions.
2. Method
2.1. IVPA/IVUS multimodality system
We designed and developed the compact system shown in Fig. 1(a). A new 1725nm, 10 kHz repetition rate, custom-made OPO high-speed laser (Photonics Industries Inc.) was used as the light source for photoacoustic excitation. The laser pulses were coupled into the rotary joint through a 105 µm core multimode fiber. The rotary joint device, consisting of a linear pullback stage for longitudinal scanning, an optical rotary joint for laser coupling, and an electrical slip ring for signal coupling, was used for motion control and the coupling of optical and electrical signals between the stationary components and the rotating IVPA/IVUS catheter. Rotation was generated by a rotary motor and transmitted to the distal end of the catheter via a torque coil. A delay generator was employed to delay 7 µs of the master trigger (t0) from the laser to activate the ultrasound pulser/receiver. The IVPA and IVUS signals are first connected and filtered by a common mode choke specifically designed and home-built for the system, then pre-amplified by a receiver and digitized with a data acquisition board (ATS9350, Alazar Technologies, Pointe-Claire, QC, Canada) at a 250 MS/s sampling rate. Finally, the digitized raw data are transferred to a personal computer for further processing and real-time display. For the experiment, imaging system was performed with the specimens immersed in saline at room temperature. The samples were not perfused during imaging.
Fig. 1.
Schematic of the experiment system. (a) Multimodal IVUS/IVPA system setup. FORJ: fiber optical rotary joint, t0: master trigger from the laser, t1: delayed trigger. (b) Illustration of the miniaturized probe inner structure. Green light: ultrasound signal path. Red light: photoacoustic light path.
2.2. Effect of common mode choke (CMC) for noise minimization
In our design, a common mode choke (CMC) is employed to reduce radio frequency (RF) noise in the ultrasound signal chain. The CMC is a passive EMI suppression component that consists of two windings on a shared magnetic core, typically a toroid [20,21]. It is specifically designed to block common mode currents, which flow in the same direction on multiple conductors, while allowing differential mode signals to pass through with minimal impedance. As shown in Fig. 1(a), the CMC was placed on the return echo ultrasound signal pathway, close to the distal imaging end of the catheter. This strategic placement ensures that unwanted common mode noise or spurious signals are attenuated before reaching the acquisition board. In differential mode operation, currents flow in opposite directions through the two windings, such as outward on one line and returning on the other. This causes the magnetic flux generated by each current to be cancelled within the core, resulting in negligible impedance to the desired signal. In common mode, however, noise currents flow in the same direction on both lines simultaneously, typically induced by external EMI sources. These currents generate magnetic flux in the same direction within each winding, which adds constructively in the core. The resulting combined flux creates a strong opposing magnetic field that leads to high inductive impedance and effectively attenuates the common mode noise. As illustrated in Fig. 2, the red and black arrows represent the additive magnetic flux paths in common mode, while the opposing fluxes in differential mode cancel each other out. This selective impedance behavior makes CMCs highly effective in suppressing common mode EMI without affecting normal signal transmission. As a result, the baseline noise in the received A-line signals is reduced, leading to improved signal stability and cleaner reconstructed IVUS images, as demonstrated in Fig. 2. To optimize performance, we first measured the current noise profile and target impedance of the transducer. A custom-made CMC was then designed to match these parameters, and the design parameters of CMC are summarized in Table 1. Experimental results demonstrated an improvement of 30 dB in EMI suppression. The signal-to-noise ratio (SNR) was calculated from the reconstructed data as the ratio between the mean signal amplitude within a selected region of interest and the standard deviation of the background noise, representing imaging quality for the entire system. The reported dynamic range refers to the display dynamic range applied to the log-compressed images for visualization.
Fig. 2.
System-level schematic of common-mode noise suppression. The highlighted red box regions indicate the baseline A-line signals used for noise comparison.
Table 1. Design parameters of CMC.
| Parameters | Value |
|---|---|
| Core material | Ferrite |
| Lines | 1 |
| Peak Impedance | 3.00 kΩ |
| Peak Attenuation | 30 dB |
| Inductance | 13 µH |
| DCR | 20 µΩ |
| Isolation | 1500 Vrms |
kΩ = kilo-ohm, dB = decibel, µH = micro-hertz, µΩ = micro-ohm, Vrms = root-mean-square voltage.
2.3. Transducer design and fabrication
2.3.1. Material selection
To improve the detection of lipid-rich plaques, a custom 28 MHz ultrasound transducer was developed in-house at the University of Southern California. While conventional IVUS systems often use transducers with center frequencies around 45 MHz to achieve high axial resolution, such high frequencies suffer from significant acoustic attenuation, which limits penetration depth and reduces sensitivity to photoacoustic signals. In contrast, a lower center frequency improves photoacoustic signal detection and enables deeper tissue penetration by reducing acoustic attenuation, as established in prior studies on ultrasound imaging physics. This advantage, however, comes with a trade-off in IVUS resolution. As a result, a center frequency of 28 MHz was chosen as an optimal compromise between maintaining sufficient structural resolution and enhancing lipid-specific signal detection. To support our design, single-crystal lead magnesium niobate-lead titanate (PMN-PT) was selected as the transducer material due to its broad bandwidth and high sensitivity at low frequencies [22].
2.3.2. Fabrication process
The fabrication process of the ultrasound transducer was conducted as follows. First, an acoustic stack was prepared, comprising a lead magnesium niobate–lead titanate (PMN-PT) single crystal, a first matching layer, and a backing layer [23]. A 28 MHz poled PMN-PT sample was prepared, and both its top and bottom surfaces were coated with Cr/Au (50/100 nm) electrodes using a sputtering system (NSC-3000 Sputter Coater, Nano-Master, Inc., Austin, TX, USA). For the first matching layer, a silver-loaded epoxy was employed, formulated from 2–3 µm silver particles (Sigma-Aldrich Inc., St. Louis, MO, USA) and a mixture of Insulcast 501 and Insulcure 9 (American Safety Technologies, Roseland, NJ, USA). Parylene C (Specialty Coating Systems, Indianapolis, IN, USA), possessing an acoustic impedance of 2.5 MRayl, was selected as the second matching layer material. The backing layer was formed using a conductive silver paste (E-Solder 3022, Von Roll Isola, New Haven, CT, USA) with an acoustic impedance of 5.9 MRayl. The materials for the first matching and backing layers were cast and cured onto the top and bottom surfaces of the PMN-PT sample, respectively. Subsequently, the entire acoustic stack was diced into individual elements with dimensions of 0.5 × 0.5 mm2 using a precision dicing saw (Tcar 864-1, Thermocarbon, Casselberry, FL, USA). A double-coaxial cable was then soldered to both sides of the stack to enable electrical connectivity. Finally, the entire device was encapsulated with a parylene C film to form the IVUS transducer [24–26]. Detailed specifications of the fabricated transducer are provided in Table 2.
Table 2. Design parameters of piezo-electric transducer.
| Parameters | Value |
|---|---|
| Center frequency (MHz) | 28 MHz |
| Piezo thickness (PMN-PT) | 70 µm |
| Element size | 0.5 mm × 0.5 mm |
| 1st matching layer thickness (Silver-epoxy) | 20 µm |
| 2nd matching layer thickness (Parylene) | 10 µm |
| Backing layer material (E-solder) | 4 µm |
MHz = megahertz, µm = micrometer, mm = millimeter.
2.4. Laser development
A customized high-speed optical parametric oscillator (OPO) laser operating at 1725nm (Photonics Industries, Bohemia, NY, USA) was employed as the excitation light source for generating photoacoustic signals. Unlike conventional light sources, this system features a repetition rate of 10 kHz, enabling a scanning speed of 30 Hz for small vessel phantoms and maintaining stable performance. The wavelength of 1725nm was specifically selected for its sensitivity to lipid detection [27–29]. While both 1200 nm and 1725nm wavelengths can visualize lipid-rich regions in atherosclerotic plaques, 1200 nm is also absorbed by other tissue types, potentially introducing interference. In contrast, 1725nm provides superior lipid-to-water absorption contrast, making it the optimal choice for this study. The laser pulse duration is approximately 15 ns; the maximum output pulse energy of the laser is around 800 µJ/pulse. Using a safe operating standard, we operate at around 150 µJ/pulse, and laser fluence of ∼0.05 J/cm2 at focal point, was within the ANSI allowed safety range (at 1.7 µm, single pulse MPE = 1 J/cm2) [30].
2.5. Imaging catheter fabrication
We designed and fabricated a novel imaging catheter, with its detailed structure illustrated in Fig. 1(b). Within the catheter, a 105 µm core multimode fiber (MMF) is used to deliver the photoacoustic (PA) excitation light. The distal tip of the fiber is polished at a 38-degree angle to achieve total internal reflection, enabling effective overlap between the optical and acoustic paths. A single-element PMN-PT transducer was integrated into a stainless-steel housing (outer diameter: 0.9 mm; inner diameter: 0.8 mm), enabling both US transmission and co-registered US/PA signal reception. The transducer housing is connected to a torque coil (outer diameter: 0.8 mm; length: ∼300 mm), which allows smooth and rotational scanning of the distal tip. To preserve signal fidelity and reduce acoustic attenuation, the rotating probe assembly was enclosed within a specially selected, transparent medical-grade imaging sheath (Pebax, Duke Extrusion Inc., CA, USA). Pebax sheaths have been widely used in the design of imaging catheters for intravascular systems such as intravascular optical coherence tomography (IVOCT) systems and IVUS imaging systems. This material was chosen for its excellent acoustic and optical transparency, which ensured minimal distortion or attenuation of the transmitted and received signals. The entire catheter assembly was carried out on a dedicated probe fabrication workstation in the lab.
3. Results
3.1. Transducer and imaging catheter characterization
Figure 3(a) is a side view of the fabricated catheter prototype, and a zoomed-in photograph of the PMN-PT transducer is shown in Fig. 3(b). The transducer is assembled in a stainless-steel housing (OD: 0.9 mm). A glass mirror was used as an imaging target in the pulse-echo test to measure the frequency response spectrum of the ultrasonic transducer made of PMN-PT crystal. The pulse echo and electrical impedance information were shown in Fig. 3(c) and (d). The transducer has a center frequency of 28 MHz and -6 dB BW of 71%. The impedance and the phase angle at 28 MHz are 34.2 ohms and -40.3 degrees, respectively.
Fig. 3.
(a) Photograph of the whole catheter prototype. (b) Fabricated PMN-PT ultrasonic transducer. (c) Pulse-echo measurements (blue) and respective frequency spectra (red). (d) Electrical Impedance (blue) and phase angle spectra (red).
To validate the spatial resolution performance of the imaging catheter for plaque characterization, a 20 µm tungsten wire phantom immersed in deionized water was used. The tungsten wires were positioned at a radial distance of 1.5 mm from the catheter center. Since no optical or acoustic focusing was applied, the lateral resolution was determined by the beam width, while the axial resolution was governed by the bandwidth of the ultrasound transducer. The axial resolutions of IVPA and IVUS were measured to be 70 µm and 65 µm, respectively. The transverse resolutions of IVPA and IVUS were 250 µm and 200 µm, respectively, at the same radial distance of 1.5 mm from the catheter center.
3.2. Comparison with cadaver artery
The imaging capability of proposed method was first tested with a tissue sample of human cadaver artery ex vivo using our catheter, as shown in Fig. 4. Figure 4(a) and (b) present IVUS artery images without and with a CMC component integrated in the signal return path, acquired at 10 Hz and 30 Hz, respectively. The result images and corresponding SNR measurements demonstrate improved system performance. A consistent SNR of approximately 21 dB across different acquisition speeds reflects the system’s high sensitivity, enabling the detection of weak signals and enhancing tissue contrast for more detailed visualization, both of which are crucial for accurate plaque characterization.
Fig. 4.
Ex vivo IVUS artery result comparison between (a) baseline & (b) CMC component on the return pathway, displayed with a 60 dB dynamic range. Scale bar: 2 mm.
3.3. Real-time experiment of IVUS/IVPA
A lipid-rich atherosclerotic plaque from a cadaver was imaged, as shown in Fig. 5. Fresh human carotid artery samples were obtained from cadavers and frozen at -20 degrees Celsius (Willed Body Program, University of California, Irvine). After imaging, the tissue was decalcified, embedded, and sectioned into -6 µm-thick slices. Finally, the slides were stained with H&E stains. Figure 5(a)-(j) display OCT images, IVUS images, IVPA images, a fused dual modality image, a formalin-fixed cross-sectional view, a microscopic image, and an H&E histology validation. In Fig. 5(a)-(c), yellow circles are visible, which correspond to the lipid region consisting of cholesterol crystals and periadventitial tissue. The large central cavity observed in the histological section corresponds to the necrotic core of the lesion, where lipids were removed during tissue processing. This area aligns with the lipid-rich region identified in the microscopic cross-section of the formalin-fixed artery. It also matches the photoacoustic signal detected by our imaging system, as well as the plaque-like structure observed in ultrasound images. These findings collectively confirm the feasibility and accuracy of our system in detecting lipid-rich atherosclerotic plaques. The irregular lumen boundary, along with the prominent intimal thickening and the fibrous, necrotic-core-like structure observed in the Hematoxylin and Eosin (H&E)–stained section, closely resembles the features identified in the previously acquired IVUS, IVPA, and IVOCT images. This correspondence also confirms that the histological section corresponds to the same anatomical location.
Fig. 5.
Images of lipid-rich atherosclerotic plaque. (a) OCT image, (b) US image, (c) PA image, (d) IVOCT, (e) IVUS, (f) IVPA, (g) Microscopic view of formalin-fixed tissue, (h) Fused IVPA-US image, (i) corresponding H&E histology, and (j) formalin-fixed artery. The blue arrows indicate the location of the lesion. Figures (a)-(f) & (h) were generated using MATLAB R2021b. Figure (f) color bar represents normalized PA amplitudes (0–1 scale). Scale bar: 2 mm.
4. Discussion and conclusion
Plaque vulnerability is a critical determinant of lesion rupture risk, yet its accurate assessment remains challenging in clinical practice. Although intravascular multimodality imaging systems incorporating photoacoustic contrast have been developed to detect lipid-rich plaques, many reported implementations have struggled to achieve reliable real-time imaging under biologically dynamic conditions [31–32]. These limitations are largely attributed to insufficient laser repetition rates and instability in system performance, which constrain imaging speed and signal fidelity during continuous scanning. Rather than introducing a new imaging mechanism, the present work addresses these challenges through targeted system-level optimization. By integrating a high-repetition-rate 1.7 µm laser source and redesigning the signal reception pathway to improve noise suppression and stability, the proposed system enables reliable, continuous intravascular scanning with improved robustness. These design choices collectively mitigate performance degradation associated with high-speed operation and enable more consistent lipid signal detection and lesion characterization.
The updated multimodality imaging system demonstrates concurrent improvements in acquisition speed, signal-to-noise ratio, and dynamic range. Photoacoustic imaging performance is fundamentally constrained by the laser pulse repetition rate, which limits the number of A-lines acquired per unit time and imposes a trade-off between spatial resolution and imaging speed. This constraint becomes particularly pronounced when imaging large-diameter arteries, where a higher number of A-lines per rotation is required to maintain lateral resolution, thereby reducing achievable rotational speed. In contrast, smaller vessels such as coronary arteries, which typically have outer diameters below 5 mm, require fewer A-lines per rotation and thus permit substantially higher rotational imaging speeds. Within this framework, the proposed system achieves rotational imaging speeds of 30 Hz while maintaining a dynamic range of approximately 60 dB for IVUS and 40 dB for IVPA imaging, with an IVPA signal-to-noise ratio of approximately 21 dB. Compared to our previous prototype operating at 1 Hz with a dynamic range of approximately 25 dB, the current system represents a substantial improvement in both imaging speed and image quality [18]. These enhancements improve tissue contrast and structural delineation, addressing prior limitations in resolving fine morphological features. In comparison, previously reported IVUS/IVPA systems have achieved dynamic ranges of approximately 35 dB (IVUS) and 20 dB (IVPA) in ex vivo studies, and approximately 32 dB (IVUS) and 18 dB (IVPA) for in vivo imaging in porcine models at rotational speeds around 20 Hz, highlighting the steady progress in the field [18].
Importantly, the increased imaging speed and improved operational stability of the proposed system extend beyond incremental performance gains. Higher rotational imaging speeds reduce motion artifacts caused by catheter instability and physiological motion, improve longitudinal sampling consistency during pullback, and enable more reliable mapping of heterogeneous lipid distributions over extended vascular segments. These capabilities enhance the practical utility of multimodality intravascular imaging under biologically relevant conditions and provide a robust foundation for future integration with additional high-speed imaging modalities, such as optical coherence tomography (OCT). From a clinical perspective, faster scanning speeds shorten imaging procedures and reduce the time required for diagnosis and intervention, potentially lowering the risk of adverse cardiovascular events. Improved sensitivity to weak photoacoustic signals and small lipid pools enables earlier and more accurate detection of lipid-rich plaques, supporting broader clinical adoption of intravascular multimodality imaging technologies.
The primary limitation of this study is the use of ex vivo arterial segments, which do not fully replicate in vivo physiological conditions such as cardiac-induced motion, pulsatile hemodynamics, and strong optical absorption by hemoglobin in flowing blood [33]. These factors may introduce additional motion artifacts and influence signal quality and imaging depth during in-vivo imaging. In addition, the relatively small sample size limits statistical power and generalizability, particularly for evaluating system performance in smaller-diameter vessels under ultrafast scanning conditions. Larger-scale studies will be necessary to further validate system performance across diverse arterial types and plaque morphologies.
Finally, while lipid accumulation serves as an important biomarker of plaque vulnerability, it represents only one component of the complex pathological landscape of atherosclerosis. Plaque vulnerability is influenced by additional features, including fibrous cap thickness, neovascularization, macrophage infiltration, and local inflammation. In particular, thin-cap fibroatheroma (TCFA), which is strongly associated with acute coronary syndromes, is characterized by a large lipid core and a thin fibrous cap [34,35]. Future development may therefore include integration with complementary imaging modalities such as polarization-sensitive OCT (PS-OCT) to enable simultaneous assessment of lipid content and fibrous cap morphology. A tri-modality system combining PS-OCT, IVUS, and IVPA could provide a more comprehensive evaluation of plaque vulnerability. Further optimization of probe design, including transparent transducers and meta-surface-based optical elements, may enhance coaxial alignment and image quality. Longitudinal in vivo studies in large animal models, followed by clinical trials, will be essential to fully assess the translational potential of the proposed system.
In conclusion, this work presents a high-speed multimodality intravascular imaging system that improves practical imaging speed and operational stability through targeted system-level optimization. By enabling stable, co-registered IVUS and IVPA imaging at 30 Hz within a compact catheter design, the proposed platform advances the usability of multimodality intravascular imaging under biologically relevant conditions. The demonstrated performance in human cadaver arteries highlights the system’s capability for robust plaque characterization over extended vascular segments and supports its potential for future translational applications.
Acknowledgements
We thank Nicole Wakida for her assistance with histological preparation and Lidek Chou for providing insightful advice on probe-making. We also acknowledge the Willed Body Program at the University of California, Irvine, for providing the cadaveric specimen used in this study.
Ethics approval. All methods were carried out in accordance with the University of California, Irvine (UCI) Institutional Review Board (IRB) and the Institutional Animal Care & Use Committee (IACUC). IRB granted an exemption to the protocol requirement since the activities do not constitute Human Subject Research. Informed consent was deemed unnecessary because the confidentiality of the deceased cadaver tissues is protected and coded. All experimental protocols were approved by the UCI IACUC under protocol # AUP-24-156.
Funding
U.S. National Institute of Health ( R01HL-125084, R01HL-177188, R01EB-030558, R01EB-030024, R01EY-028662); United States Air Force Office of Scientific Research https://ror.org/011e9bt93 ( FA9550-23- 1-0685).
Disclosures
The authors declare no conflicts of interest.
Data Availability
Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon reasonable request.
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Associated Data
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Data Availability Statement
Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon reasonable request.