Three-dimensional noninvasive rat cardiac photoacoustic tomography

As a non-invasive detection technology emerging in recent years, photoacoustic tomography can perform functional imaging of the optical properties of biological tissues with high temporal and spatial resolution.

However, without surgical thoracotomy, the imaging quality of photoacoustic tomography in the cardiovascular field has been limited by illumination methods and detection techniques, which cannot clearly reveal the anatomy of the entire heart and the dynamics of the vascular system.

Recently, Lihong V. Wang’s team at Caltech used the recently developed three-dimensional photoacoustic tomography (3D-PACT) platform to perform three-dimensional noninvasive imaging of rat hearts, reducing the effects of optical attenuation and acoustic distortion through the chest cavity by improving illumination and detection, and synchronizing measurements with ECG detection, thereby clearly demonstrating the dynamic anatomy of the heart.

The technique can in turn be used to reveal structural and functional differences in the heart, such as chamber size, heart wall thickness, and hemodynamic changes, between healthy, hypertensive, and obese rats. 3D-PACT, a rat-based non-invasive application, will facilitate the research and diagnosis of animal models, and is expected to benefit cardiovascular imaging in human newborns through clinical translation.

The results were published in Light: Science & Applications under the title “Non-invasive Photoacoustic Computed Tomography of Rat Heart Anatomy and Function.” Lin Li of Zhejiang University and Xin Tong of Caltech are co-first authors, and Tzung K. Hsiai of UCLA and Lihong V. Wang of Caltech are co-corresponding authors.

As one of the diseases with the highest mortality rate in the world, cardiovascular disease has been extensively studied clinically and in animal experiments, and non-invasive detection of the heart region plays a crucial role in this.

At present, mainstream cardiovascular non-invasive imaging techniques include echocardiography, magnetic resonance imaging, X-ray tomography and positron emission tomography, and these technologies have their own advantages and disadvantages in spatial resolution, field of view, and scope of application.

In recent years, photoacoustic imaging as an emerging non-invasive imaging technology has attracted increasing attention. Because it combines optical illumination and acoustic detection, it has both the penetration depth and high temporal and spatial resolution of molecular absorption spectroscopy for optical imaging and ultrasonic imaging. At the same time, photoacoustic imaging does not require magnetic fields, ionizing radiation, or injection of contrast agents, so it has unique advantages in terms of safety, portability, and construction cost.

Despite the advantages and features described above, the research of photoacoustic imaging in the field of heart has been limited, especially the image quality of non-invasive 3D imaging has not been ideal for a long time, for three main reasons.

First, the heart is partially surrounded by ribs and lungs, which hinder the transmission of ultrasound to a certain extent, resulting in limited ultrasound detection quality.

Secondly, photoacoustic imaging relies on the optical absorption of molecules, and the heart, as the center of blood circulation, has extremely high levels of hemoglobin and myoglobin, which limits the penetration depth of excitation light in tissues.

Third, in vivo imaging of the heart is generally affected by the heartbeat cycle. The heartbeat cycle provides rich information about blood flow dynamics on the one hand, and on the other hand, it also blurs the image and affects the image quality.

In recent years, Caltech Wang’s team has built a series of photoacoustic tomography equipment, which is suitable for the study of different resolutions, different viewing angles, and different biological samples. Among them, a hemispherical photoacoustic tomography system called 3D-PACT successfully demonstrated the vascular distribution of human brain, breast and rat brain.

Recently, based on this system, the team adopted electrocardiogram synchronous detection technology, and further optimized the lighting and detection structure design, so as to clearly display the three-dimensional photoacoustic image of the beating heart of a living rat for the first time. Based on the high spatial and temporal resolution of this series of images, the team systematically analyzed and compared multiple cardiovascular parameters (such as ventricular/atrial volume, heart wall thickness, hemodynamic changes in major blood vessels) in three rats (normal, obese, and hypertension), demonstrating the unique potential of this system and photoacoustic imaging in the field of cardiovascular clinical imaging.

Experimental process and results

Figure 1: Schematic diagram of the structure of the 3D-PACT system, the experimental process of rats, and the synchronous detection process of electrocardiogram.

In terms of acoustic detection, the 3D-PACT system consists of an array of 4 arc-shaped ultrasonic detectors that can perform a dense scan of 90° around the center of the sphere, resulting in a hemispherical detection matrix within 10 seconds, with spatial resolution suitable for the size of the rat’s blood vessels.

In terms of optical illumination, the system is equipped with a near-infrared nanosecond pulsed laser with a repetition rate of 50 Hz to perform intensive time sampling of the heartbeat cycle.

In addition, in order to capture the dynamic information of the heartbeat cycle, the system is equipped with ECG sampling equipment, and the ECG detection is performed synchronously in the imaging scanning interval.

Finally, the ECG curve and photoacoustic data will be synchronized, and heart signals of the same phase in different cycles will be superimposed, averaged, and reconstructed to form a dynamic three-dimensional heart image.

Figure 2: Image of photoacoustic structure of different phases of rat cardiac beating cycle.

The reconstructed image shows the periodic movement of the heart, and the major blood vessels around the heart (such as the aorta, pulmonary artery, coronary artery, etc.) are also clearly visible. To compare the differences in heart structure in normal, obese, and hypertensive rats, the team used the same process to collect heart images from multiple rats and extracted the following data from them.

Firstly, based on the static image of the middle layer section, there was a statistically significant difference in the thickness of the left and right ventricular walls between normal and obese rats.

Secondly, based on the three-dimensional dynamic image, the volume changes of the atria and ventricles of normal, obese and hypertensive rats had their own characteristics.

Finally, based on multi-sectional dynamic images, the trends of photoacoustic signal changes (indirectly reflecting blood flow dynamics) in the main blood vessels of normal, obese and hypertensive rats were also different.

The above observations are consistent with data such as ex vivo profiles, which in turn verifies the ability of 3D-PACT to capture cardiac dynamics.

Figure 3: Atrium/ventricle and vascular signals as a function of cardiac cycle in normal, obese, and hypertensive rats.

In this work, the researchers improved and optimized the 3D photoacoustic tomography system to show for the first time a clear 3D photoacoustic dynamic image of the rat’s pulsating heart, and analyzed various structural and functional differences in the heart of normal, obese, and hypertensive rats.

This non-invasive imaging system combines high-speed, high-resolution, optical absorption spectrum imaging, and hopes to realize more potential in clinical fields such as human neonatal cardiac imaging. (Source: LightScience Applications WeChat public account)

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