Intravascular Photoacoustic Imaging Research Articles

Intravascular photoacoustic and optical coherence tomography imaging dual-mode system for detecting spontaneous coronary artery dissection: A feasibility study

In this work, we present an intravascular dual-mode endoscopic system capable of both intravascular photoacoustic imaging (IVPAI) and intravascular optical coherence tomography (IVOCT) for recognizing spontaneous coronary artery dissection (SCAD) phantoms. IVPAI provides high-resolution and high-penetration images of intramural hematoma (IMH) at different depths, so it is especially useful for imaging deep blood clots associated with imaging phantoms. IVOCT can readily visualize the double-lumen morphology of blood vessel walls to identify intimal tears. We also demonstrate the capability of this dual-mode endoscopic system using mimicking phantoms and biological samples of blood clots in ex vivo porcine arteries. The results of the experiments indicate that the combined IVPAI and IVOCT technique has the potential to provide a more accurate SCAD assessment method for clinical applications.

A high-sensitivity high-resolution intravascular photoacoustic catheter through mode cleaning in a graded-index fiber

Intravascular photoacoustic imaging has been developed to evaluate the possibility of plaque rupture in atherosclerosis by high spatial resolution imaging of lipid. However, the detection sensitivity and spatial resolution are compromised by the poor focusing caused by a multimode fiber. In this work, we report an intravascular photoacoustic catheter with mode self-cleaning in a graded-index fiber to improve the beam quality and the sensitivity for lipid detection. Compared with the higher-order modes in a step-index multimode fiber, the lower-order modes generated by the self-cleaning effect in the graded-index fiber greatly enhanced the photoacoustic spatial resolution and detection sensitivity. The dominant ringing artifact caused by laser absorption of the ultrasound transducer was further reduced by using stripe suppression. A lipid plaque mimicking phantom was imaged for evaluation. Lipid particles with a small diameter of 75.7 µm were clearly observed.

A Deep Learning Method for Motion Artifact Correction in Intravascular Photoacoustic Image Sequence.

In vivo application of intravascular photoacoustic (IVPA) imaging for coronary arteries is hampered by motion artifacts associated with the cardiac cycle. Gating is a common strategy to mitigate motion artifacts. However, a large amount of diagnostically valuable information might be lost due to one frame per cycle. In this work, we present a deep learning-based method for directly correcting motion artifacts in non-gated IVPA pullback sequences. The raw signal frames are classified into dynamic and static frames by clustering. Then, a neural network named Motion Artifact Correction (MAC)-Net is designed to correct motion in dynamic frames. Given the lack of the ground truth information on the underlying dynamics of coronary arteries, we trained and tested the network using a computer-generated dataset. Based on the results, it has been observed that the trained network can directly correct motion in successive frames while preserving the original structures without discarding any frames. The improvement in the visual effect of the longitudinal view has been demonstrated based on quantitative evaluation of the inter-frame dissimilarity. The comparison results validated the motion-suppression ability of our method comparable to gating and image registration-based non-learning methods, while maintaining the integrity of the pullbacks without image preprocessing. Experimental results from in vivo intravascular ultrasound and optical coherence tomography pullbacks validated the feasibility of our method in the in vivo intracoronary imaging scenario.

Survival intravascular photoacoustic imaging of lipid-rich plaque in cholesterol fed rabbits.

Intravascular photoacoustic (IVPA) imaging is a promising modality for quantitative assessment of lipid-laden atherosclerotic plaques. Yet, survival IVPA imaging of the same plaque in the same animal is not demonstrated. Here, using a sheathed IVUS/PA catheter of 0.9 mm in diameter, we demonstrate MRI-guided survival IVPA imaging of same plaque in an aorta of a well-established rabbit model mimicking atherosclerosis in human patients. The IVUS/PA results were confirmed by histology. These advances open the opportunity to evaluate the effectiveness of a therapy that aims to reduce the size of atherosclerotic plaques and demonstrates the potential of translating the IVPA catheter into clinic for detection of lipid-rich plaques that are at high risk for thrombosis.

In vivo safety study using radiation at wavelengths and dosages relevant to intravascular imaging.

.SignificanceIntravascular photoacoustic (IVPA) imaging can identify native lipid in atherosclerotic plaques in vivo. However, the large number of laser pulses required to produce 3D images is a safety concern that has not been fully addressed.AimWe aim to evaluate if irradiation at wavelengths and dosages relevant to IVPA imaging causes target vessel damage.ApproachWe irradiate the carotid artery of swine at one of several energy dosages using radiation at 1064 or 1720 nm and use histological evaluation by a pathologist to identify dose-dependent damage.ResultsMedia necrosis was the only dose-dependent form of injury. Damage was present at a cumulative fluence of when using 1720 nm light. Damage was more equivocally identified at using 1064 nm.ConclusionsIn prior work, IVPA imaging of native lipid in swine has been successfully conducted below the damage thresholds identified. This indicates that it will be possible to use IVPA imaging in a clinical setting without damaging vessel tissue. Future work should determine if irradiation causes an increase in blood thrombogenicity and confirm whether damaged tissue will heal over longer time points.

Review on Laser Technology in Intravascular Imaging and Treatment.

Blood vessels are one of the most essential organs, which nourish all tissues in our body. Once there are intravascular plaques or vascular occlusion, other organs and circulatory systems will not work properly. Therefore, it is necessary to detect abnormal blood vessels by intravascular imaging technologies for subsequent vascular treatment. The emergence of lasers and fiber optics promotes the development of intravascular imaging and treatment. Laser imaging techniques can obtain deep vascular images owing to light scattering and absorption properties. Moreover, photothermal and photomechanical effects of laser make it possible to treat vascular diseases accurately. In this review, we present the research progress and applications of laser techniques in intravascular imaging and treatment. Firstly, we introduce intravascular optical coherent tomography and intravascular photoacoustic imaging, which can obtain various information of plaques. Multimodal intravascular imaging techniques provide more information about intravascular plaques, which have an essential influence on intravascular imaging. Secondly, two laser techniques including laser angioplasty and endovenous laser ablation are discussed for the treatment of arterial and venous diseases, respectively. Finally, the outlook of laser techniques in blood vessels, as well as the integration of laser imaging and treatment are prospected in the section of discussions.

Mesoporous, anisotropic nanostructures from bioinspired polymeric catecholamine neurotransmitters and their potential application as photoacoustic imaging agents.

Mesoporous polydopamine (PDA) nanobowls, which can be prepared using Pluronic® F-127, ammonia, and 1,3,5-trimethylbenzene (TMB), are one of the most studied anisotropic nanoparticle systems. However, only limited reports on polymerised analogues polynorepinephrine (PNE) and polyepinephrine (PEP) exist. Herein, we present modifications to a one-pot, soft template method, originally applied to make PDA nanobowls, to fabricate new shape-anisotropic nanoparticles (mesoporous nanospheres or "nano-golf balls" and nanobowls) using PNE and PEP for the first time. These modifications include the use of different oil phases (TMB, toluene and o-xylene) and ammonia concentrations to induce anisotropic growth of PDA, PNE, and PEP particles. Moreover, this work features the application of oddly shaped PDA, PNE, and PEP nanoparticles as intravascular photoacoustic imaging enhancers in Intralipid®-India ink-based tissue-mimicking phantoms. Photoacoustic imaging experiments showed that mesoporous nanobowls exhibit stronger enhancement, in comparison to their mesoporous nano-golf ball and nanoaggregate counterparts. The photoacoustic enhancement also followed the general trend PDA > PNE > PEP due to the differences in the rates of polymerisation of the monomers and the optical absorption of the resulting polymers. Lastly, about two- to four-fold enhancement in photoacoustic signals was observed for the mesoporous nanostructures, when compared to smooth nanospheres and their nano-aggregates. These results suggest that shape manipulation can aid in overcoming the inherently lower performance of PNE and PEP as photoacoustic imaging agents, compared to PDA. Since nanomaterials with mesoporous and anisotropic morphologies have significant, unexplored potential with emerging applications, these results set the groundwork for future studies on photoacoustically active oddly shaped PNE- and PEP-based nanosystems.

Suppression of motion artifacts in intravascular photoacoustic image sequences.

Intravascular photoacoustic (IVPA) imaging is an image-based imaging modality for the assessment of atherosclerotic plaques. Successful application of IVPA for in vivo coronary arterial imaging requires one overcomes the challenge of motion artifacts associated with the cardiac cycle. We propose a method for correcting artifacts owing to cardiac motion, which are observed in sequential IVPA images acquired by the continuous pullback of the imaging catheter. This method groups raw photoacoustic signals into subsets corresponding to similar phases in the cardiac cycles. Thereafter, the sequential images are reconstructed, by representing the initial pressure distribution on the vascular cross-sections based on the clustered frames of signals by time reversal. Results of simulation data demonstrate the efficacy of this method in suppressing motion artifacts. Qualitative and quantitative evaluations of the method indicate an enhancement of the image quality. Comparison results reveal that this method is computationally efficient in motion correction compared with the image-based gating.

In vivo intravascular photoacoustic imaging at a high speed of 100 frames per second.

Intravascular photoacoustic (IVPA) imaging technology enables the visualization of pathological characteristics (such as inflammation activities, lipid deposition) of the artery wall. Blood flushing is a necessary step in improving the imaging quality in in vivo IVPA imaging. But the limited imaging speed of the systems stretches their flushing time, which is an important obstacle of their clinical translations. In this paper, we report an improvement in IVPA/IVUS imaging speed to 100 frames per second. The high-speed imaging is demonstrated in rabbit in vivo, visualizing the nanoparticles accumulated on abdominal aorta wall at the wavelength of 1064 nm, in real time display. Blood flushing in vivo improves the IVPA signal-noise-ratio by around 3.5 dB. This study offers a stable, efficient and easy-to-use tool for instantaneous disease visualization and disease diagnosis in research and forwards IVPA/IVUS imaging technology towards clinical translations.

Reliability assessment on intravascular photoacoustic imaging of lipid: ex vivo animal and human sample validation.

Although the lipid-detecting IVPA imaging system has been developed in resolution, speed, and catheter size, there is no parameterization study of the reliability on the IVPA imaging for lipid diagnosis. Here, the sensitivity, specificity, and accuracy were calculated to assess the reliability of the IVPA imaging of lipid. Abdominal aortas from six rabbits with atherosclerosis, were subjected to the IVPA imaging and Oil Red O staining, and 75 groups of IVPA as well as corresponding histological images were obtained. Similarly, 125 groups of IVPA and histological results were obtained from five human carotid plaque samples. The sensitivity, specificity, and accuracy, calculated from the statistical data, were 96.8%, 83.3%, 94.6% and 97.3%, 72.7%, 95.2%, respectively. The numerical values of sensitivity, specificity, and accuracy demonstrated the reliability of IVPA imaging on distinguishing the lesions vessel with lipid-rich plaque, which provided the foundation for IVPA translation to clinical application.

Intravascular Photoacoustic and Autofluorescence Imaging for Detecting Intraplaque Hemorrhage: A Feasibility Study

Intraplaque hemorrhage (IPH), which is a trigger and conveys all blood components into the plaque, influencing the cholesterol crystal formation and retention, haemoglobin and oxidative enzymes, and blood-borne proteolytic activity. IPH is one of the key determinants for plaque vulnerability. In this paper, we proposed a dual-modality endoscope probe with a diameter of 1 mm for simultaneously detecting the lipid core and IPH, our system was composed of photoacoustic imaging (PAI) and near-infrared auto-fluorescence imaging (NIRAFI). The lipid as endogenous marker of intravascular PAI could visualize the lipid distribution of atherosclerotic plaque, and bilirubin as the marker of intravascular NIRAFI was used to locate and quantify the IPH. The phantom and ex vivo rabbit aorta experiments had proved the feasibility and capability of the dual-mode probe for imaging IPH and lipid core expansion. And the results indicated that the dual-mode intravascular endoscope had the potential for accurately detecting IPH in atherosclerotic plaques.

Front Cover

A dual‐frequency intravascular photoacoustic/ultrasound catheter is developed and validated for lipid‐rich atherosclerotic plaque detection. By combining low‐frequency transducer for highly sensitive lipid detection and high‐frequency transducer for accurate localization in a single catheter with 1 mm diameter, this dual‐frequency catheter design largely improves the performance of intravascular photoacoustic imaging. It takes a step forward for the translation of this imaging modality for identification of vulnerable plaque in the vascular wall and perivascular lipid.Further details can be found in the article by Yingchun Cao, Mouhamad Alloosh, Michael Sturek, and Ji‐Xin Cheng (e202000004). image

High-robustness intravascular photoacoustic endoscope with a hermetically sealed opto-sono capsule.

The prevailing open-structure intravascular photoacoustic (IVPA) endoscope emits a gradually deformed laser beam with exposed optical or acoustical components bearing pollution and damage in arterial lumen. Deformed laser beam scanning, which causes a low excitation efficiency and serious deterioration of the transverse resolution, is a current big obstacle to the application of photoacoustic endoscopy in intravascular imaging. Hence, the stable and reliable IVPA endoscope is indispensable. In this letter, we designed a high-robustness intravascular photoacoustic (HR-IVPA) endoscope with a hermetically sealed opto-sono capsule. The distal end of the opto-sono capsule was integrated with miniaturized optics, including a customized C-Lens and a customized total-reflection prism (TRP). The TRP was first applied to a side-viewing IVPA endoscope, featuring a high-throughput energy coupling efficiency of 90% and a cut-off free damage threshold. The optical path structure of the endoscope, optimized using optical simulation tools, overcame the ambiguous focus shift caused by chromatic dispersion and achieved a waist size of 20 µm as well as a focus depth of 4 mm in water at the wavelength of 1200 nm. The mass phantom experiments demonstrated that the HR-IVPA endoscope afforded repeatable IVPA images with a relatively constant signal-to-noise ratio (SNR) of about ∼41.8 dB and a transverse resolution of about ∼23 µm. The imaging experiments of the stent and lipid further demonstrated the robustness and validated the imaging ability of the HR-IVPA endoscope, which opens a new avenue for improving the endoscopic imaging capability, strengthening the credible detection of atherosclerotic cardiovascular disease.

Ultrafine intravascular photoacoustic endoscope with a 0.7 mm diameter probe.

Intravascular photoacoustic (IVPA) imaging, benefiting from high optical contrast, large imaging depth and absorption specificity, is of great potential for lipid-rich plaque detection. However, the diameters of reported IVPA endoscopes are too big to intervene into the coronary artery branches. Here, by designing an ultracompact house embedded with a side-fire fiber and a miniature single-element ultrasound transducer, we developed an ultrafine IVPA endoscope with a diameter of 0.7mm aiming at coronary artery branches atherosclerotic plaque detection. The reliability and feasibility of the ultrafine IVPA endoscope was demonstrated by imaging a stent with a 1.6mm inner diameter. Furthermore, the photoacoustic imaging and ultrasound imaging of a mouse thoracic aorta with an inner diameter of 1.15mm was conducted to verify the clinical potentiality of the endoscope, and the PA images have good consistency with histological staining results. To the best of our knowledge, this is the first time we have achieved the IVPA imaging in fine vessel by the 0.7mm diameter ultrafine photoacoustic endoscope, which paved a way for the translation of the IVPA endoscope to clinical application.

Interference-free Detection of Lipid-laden Atherosclerotic Plaques by 3D Co-registration of Frequency-Domain Differential Photoacoustic and Ultrasound Radar Imaging

As lipid composition of atherosclerotic plaques is considered to be one of the primary indicators for plaque vulnerability, a diagnostic modality that can sensitively evaluate their necrotic core is highly desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection modality that provides lipid-specific chemical information of arterial walls. Within the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications because lipid exhibits a strong absorption peak at that wavelength. However, other arterial tissues also show some degree of absorption near 1210 nm and generate undesirable interfering PA signals. In this study, a novel wavelength-modulated Intravascular Differential Photoacoustic Radar (IV-DPAR) modality was introduced as an interference-free detection technique for a more accurate and reliable diagnosis of plaque progression. By using two low-power continuous-wave laser diodes in a differential manner, IV-DPAR could efficiently suppress undesirable absorptions and system noise, while dramatically improving system sensitivity and specificity to cholesterol, the primary ingredient of plaque necrotic core. When co-registered with intravascular ultrasound imaging, IV-DPAR could sensitively locate and characterize the lipid contents of plaques in human atherosclerotic arteries, regardless of their size and depth.

High-resolution photoacoustic endoscope through beam self-cleaning in a graded index fiber.

Intravascular photoacoustic imaging can potentially improve the identification of lipid-laden atherosclerotic plaque. Most intravascular photoacoustic endoscopes use multimode fibers, which do not allow tight focusing of photons. Recent experiments on pulse propagation in multimode graded-index fibers have shown a nonlinear improvement in beam quality. Here, we harness this nonlinear phenomenon for fiber-delivery of nanosecond laser pulses. We built a photoacoustic catheter 1.4mm outer diameter, offering a lateral resolution as fine as 30μm within a depth range of 2.5mm. Such resolution is one order of magnitude better than current multimode fiber-based intravascular photoacoustic catheters. At the same time, the delivered pulse energy can reach as high as 20μJ, which is two orders of magnitude higher than that of an optical resolution photoacoustic endoscope built with a single mode fiber. These improvements are expected to promote the biomedical application of photoacoustic endoscopes which require both high resolution and high pulse energy.

Frequency-domain differential photoacoustic radar: theory and validation for ultrasensitive atherosclerotic plaque imaging.

.Lipid composition of atherosclerotic plaques is considered to be highly related to plaque vulnerability. Therefore, a specific diagnostic or imaging modality that can sensitively evaluate plaques’ necrotic core is desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information from an arterial wall with great optical contrast and long acoustic penetration depth. While, in the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications since lipids exhibit a strong absorption peak at that wavelength, the sensitivity problem arises in the conventional single-ended systems as other arterial tissues also show some degree of absorption near that spectral region, thereby generating undesirably interfering photoacoustic (PA) signals. A theory of the high-frequency frequency-domain differential photoacoustic radar (DPAR) modality is introduced as a unique detection technique for accurate and molecularly specific evaluation of vulnerable plaques. By assuming two low-power continuous-wave optical sources at and in a differential manner, DPAR theory and the corresponding simulation/experiment studies suggest an imaging modality that is only sensitive and specific to the spectroscopically defined imaging target, cholesterol.

Tapered fiber-based intravascular photoacoustic endoscopy for high-resolution and deep-penetration imaging of lipid-rich plaque.

High-resolution intravascular photoacoustic (IVPA) imaging can potentially improve the identification of atherosclerosis plaque. However, the absorption of water and the low coupled laser energy resulted in insufficient excitation energy provided by the single-mode fiber-based IVPA endoscope to achieve high-resolution and deep-penetration plaque imaging. In this paper, we developed a 1 mm diameter IVPA endoscope assembled with a Ø25-Ø9 μm tapered fiber. Owing to high coupling efficiency and the small output facula of tapered fiber, the IVPA endoscope has an optimal lateral resolution of 18 μm and a large imaging-depth covering from the intima to the peri-adventitial adipose, as confirmed by imaging results respectively. Furthermore, IVPA imaging in the blood has confirmed that the tapered fiber-based endoscope can display the distribution and the relative concentration of lipid in ex vivo plaque precisely. By the obtained histology-like images, IVPA imaging shows great potential for accurately imaging atherosclerosis plaque.

In vivo intravascular photoacoustic imaging of plaque lipid in coronary atherosclerosis.

Prospective identification of lipid-rich vulnerable plaque has remained an elusive goal. Intravascular photoacoustics, a hybrid optical and ultrasonic technology, was developed as a tool for lipid-rich plaque imaging. Here, we present the first in vivo images of lipid-rich coronary atherosclerosis acquired with this new technology in a large animal model, and relate them to independent catheter-based imaging and histology.

An FPGA-Based Backend System for Intravascular Photoacoustic and Ultrasound Imaging.

The integration of intravascular ultrasound (IVUS) and intravascular photoacoustic (IVPA) imaging produces an imaging modality with high sensitivity and specificity which is particularly needed in interventional cardiology. Conventional side-looking IVUS imaging with a single-element ultrasound (US) transducer lacks forward-viewing capability, which limits the application of this imaging mode in intravascular intervention guidance, Doppler-based flow measurement, and visualization of nearly, or totally blocked arteries. For both side-looking and forward-looking imaging, the necessity to mechanically scan the US transducer limits the imaging frame rate, and therefore, array-based solutions are desired. In this paper, we present a low-cost, compact, high-speed, and programmable imaging system based on a field-programmable gate array suitable for dual-mode forward-looking IVUS/IVPA imaging. The system has 16 US transmit and receive channels and functions in multiple modes including interleaved photoacoustic (PA) and US imaging, hardware-based high-frame-rate US imaging, software-driven US imaging, and velocity measurement. The system is implemented in the register-transfer level, and the central system controller is implemented as a finite-state machine. The system was tested with a capacitive micromachined ultrasonic transducer array. A 170-frames-per-second (FPS) US imaging frame rate is achieved in the hardware-based high-frame-rate US imaging mode while the interleaved PA and US imaging mode operates at a 60-FPS US and a laser-limited 20-FPS PA imaging frame rate. The performance of the system benefits from the flexibility and efficiency provided by the low-level implementation. The resulting system provides a convenient backend platform for research and clinical IVPA and IVUS imaging.