Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of excess fat in the liver without excessive alcohol consumption. Failure to detect NAFLD in advance can lead to fatal and irreversible liver diseases such as liver fibrosis, cirrhosis, and liver cancer, and thus the clinical need for rapid diagnosis of NAFLD is being raised. However, conventional NAFLD diagnostic methods, including biopsy and imaging, have inherent limitations due to technical or cost issues. For example, liver biopsy is invasive, MRI imaging is very expensive, CT is harmful for routine clinical use, and ultrasound is not very specific in diagnosing NAFLD. Here, we present photothermal strain imaging (pTSI), which uses the difference in thermal strain between fat and water during temperature change, as a new method for NAFLD diagnosis. The pTSI is a non-invasive, convenient, and cost-effective method of using a laser that matches the optical characteristics of the target. We developed a liver pTSI system to find fat accumulated in the liver using a clinical ultrasound imaging system and a lipid-sensitive continuous-wave laser. To demonstrate the feasibility of the pTSI system, in vitro experiments were performed using fat and chicken breast. The results showed that fat in the chicken breast was clearly distinguished. Finally, we performed in vivo experiments using NAFLD and normal rat. Through the difference in the strains that occurs when the laser heats the target, the progression of NAFLD could be determined.
Vulnerable plaque is the one of the leading causes of cardiovascular disease occurrence. However, conventional intravascular imaging techniques suffer from difficulty in finding vulnerable plaque due to limitation such as lack of physiological information, imaging depth, and depth sensitivity. Therefore, new techniques are needed to help determine the vulnerability of plaque, Thermal strain imaging (TSI) is an imaging technique based on ultrasound (US) wave propagation speed that varies with temperature of medium. During temperature increase, strain occurs in the medium and its variation tendency is depending on the type of tissue, which makes it possible to use for tissue differentiation. Here, we demonstrate laser-induced photo-thermal strain imaging (pTSI) to differentiate tissue using an intravascular ultrasound (IVUS) catheter and a 1210-nm continuous-wave laser for heating lipids intensively. During heating, consecutive US images were obtained from a custom-made phantom made of porcine fat and gelatin. A cross correlation-based speckle-tracking algorithm was then applied to calculate the strain of US images. In the strain images, the positive strain produced in lipids (porcine fat) was clearly differentiated from water-bearing tissue (gelatin). This result shows that laser-induced pTSI could be a new method to distinguish lipids in the plaque and can help to differentiate vulnerability of plaque.
Vulnerable plaques are the major cause of cardiovascular disease, but they are difficult to detect with conventional intravascular imaging techniques. Techniques are needed to identify plaque vulnerability based on the presence of lipids in plaque. Thermal strain imaging (TSI) is an imaging technique based on ultrasound (US) wave propagation speed, which varies with the medium temperature. In TSI, the strain that occurs during tissue temperature change can be used for lipid detection because it has a different tendency depending on the type of tissue. Here, we demonstrate photothermal strain imaging (pTSI) using an intravascular ultrasound catheter. pTSI is performed by slightly and selectively heating lipid using a relatively inexpensive continuous laser source. We applied a speckle-tracking algorithm to US B-mode images for strain calculations. As a result, the strain produced in porcine fat was different from the strain produced in water-bearing gelatin phantom, which made it possible to distinguish the two. This suggests that pTSI could potentially be a way of differentiating lipids in coronary artery.
Atherosclerosis, the most common cause of death, kills suddenly by arterial occlusion by thrombosis, which is caused by plaque rupture. Because a growing necrotic core is highly related to plaque rupture in atherosclerosis, distinguishing between fibrous plaque and lipid-rich plaque in real time is important, but has been challenging. Real-time photoacoustic imaging requires a pulse laser with high repetition rate, which tends to sacrifice pulse energy. Furthermore, a high repetition rate is hard to achieve at lipid-sensitive wavelengths, such as 1210 nm and 1720 nm. To address the unmet need, we have developed the algorithm for PA imaging. We successfully acquired ex vivo PA images from the lipid cores of arterial plaques in rabbit arteries, using a low-power 1064-nm laser. PA images were acquired with a custom-made catheter employing a single-element 40-MHz ultrasound transducer and a compact 1064-nm laser with the pulse energy of 5 μJ and the repetition rate of 24 kHz. Acquired raw data were processed in the time and frequency domains. In the time domain, a delay-and-sum algorithm was used for image enhancement. In the frequency domain, signals exceeding the MTF were removed. As a result, SNR was increased by about 10 dB without degrading spatial resolution. We were able to achieve high-speed and high-SNR lipid target imaging in animals in spite of the low lipid sensitivity of a 1064nm laser. These results show good promise for detecting lipid-rich plaques with a compact high-speed laser, which can be easily adapted for target clinical applications.
In cardiology, a vulnerable plaque is considered to be a key subject because it is strongly related to atherosclerosis and acute myocardial infarction. Because conventional intravascular imaging devices exhibit several limitations with regard to vulnerable plaque detection, the need for an effective lipid imaging modality has been continuously suggested. Photoacoustic (PA) imaging is a medical imaging technique with a high level of ultrasound (US) resolution and strong optical contrast. In this study, we successfully developed an integrated intravascular photoacoustic/ultrasound (IV-PAUS) imaging system with a catheter diameter of 1.2 mm for lipid-rich atherosclerosis imaging. An Nd:YAG pulsed laser with an excitation wavelength of 1064 nm was utilized. IV-PAUS offers 5-mm depth penetration and axial and lateral PA imaging resolutions of 94 μm and 203 μm, respectively, as determined by imaging a 6-μm carbon fiber. We initially obtained 3-dimensional (3D) co-registered PA/US images of metal stents. Subsequently, we successfully obtained 3D coregistered PA/US ex vivo images using an iliac artery from a rabbit atherosclerosis model. Accordingly, lipid-rich plaques were sufficiently differentiated from normal tissue in the ex vivo experiment. We validated these findings histologically to confirm the lipid content.
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