Photoacoustic imaging has been a focus of research for clinical applications owing to its ability for deep visualization with optical absorption contrast. However, there are various technical challenges remaining for this technique to find its place in clinics. One of the challenges is the occurrence of reflection artifacts. The reflection artifacts may lead to image misinterpretation. Here we propose a new method using multiple wavelengths for identifying and removing the reflection artifacts. By imaging the sample with multiple wavelengths, the spectral response of the features in the photoacoustic image is obtained. We assume that the spectral response of the reflection artifact is better correlated with the proper image feature of its corresponding absorber than with other features in the image. Based on this, the reflection artifacts can be identified and removed. Here, we experimentally demonstrated the potential of this method for real-time identification and correction of reflection artifacts in photoacoustic images in phantoms as well as in vivo using a handheld photoacoustic imaging probe.

The deep imaging capability and optical absorption contrast offered by photoacoustic imaging promote the use of this technology in clinical applications. By exploiting the optical absorption properties of endogenous chromophores such as hemoglobin and lipid, molecular information at a depth of a few centimeters can be unveiled. This information shows promise to reveal lesions indicating early stage of various human diseases, such as cancer and atherosclerosis. In addition, the use of exogenous contrast agents can further extend the capability of photoacoustic imaging in clinical diagnosis and treatment. In this review, the current state of the art and applications of photoacoustic molecular probes will be critically reviewed, as well as some spearheading translational efforts that have taken place over the past 5 years. Some of the most critical barriers to clinical translation of this novel technology will be discussed, and some thoughts will be given on future endeavors and pathways.

The occurrence of artifacts is a major challenge in photoacoustic imaging. The artifacts negatively affect the quality and reliability of the images. An approach using multiwavelength excitation has previously been reported for in-plane artifact identification. Yet, out-of-plane artifacts cannot be tackled with this method. Here we propose a new method using ultrasound transducer array displacement. By displacing the ultrasound transducer array axially, we can de-correlate out-of-plane artifacts with in-plane image features and thus remove them. Combining this new method with the previous one allows us to remove potentially completely both in-plane and out-of-plane artifacts in photoacoustic imaging. We experimentally demonstrate this with experiments in phantoms as well as in vivo. IntroductionRecent research has shown numerous potential clinical applications of photoacoustic imaging (PAI) [1][2][3]. This imaging technique is based on the photoacoustic (PA) effect. Samples are illuminated using short pulsed laser light. The local absorption of light generates ultrasound (US) waves which are then detected by a US transducer. PA images are reconstructed from the detected signals providing localized information about optical absorption properties of the samples. In clinical applications, the obtained information of endogenous chromophores such as hemoglobin helps diagnosing early stages of various diseases [2,[4][5][6]. A typical PAI system basically consists of a light source and US transducer array. The transducer array can be classified as one-dimensional or two-dimensional [7]. While the twodimensional transducer array provides 3D images, it requires significant users' effort and experience for acquiring and interpreting these 3D images [8]. Additionally, two-dimensional transducer arrays and the associated scanners are unaffordable for many clinical applications [8]. One-dimensional transducer arrays, in contrast, are widely used for clinical studies [9,10], so from the point of view of clinical translation the incorporation of PAI in a one-dimensional array is preferred.Several compact and low-cost PAI systems for clinical use have been developed. Integrating a laser source into a handheld US probe stands out among the approaches [9-12]. However, the occurrence of artifacts related to acoustic inhomogeneity of the tissue (clutter) is a major drawback of using a linear US transducer array. The artifacts aimed in this work include in-plane artifacts (IPAs), also called reflection artifacts, and out-of-plane artifacts (OPAs). While IPAs are caused by signals being reflected inside the imaging plane, OPAs are caused by absorbers located outside the imaging plane of the transducer array [13,14]. These artifacts appear as real image features, such as blood vessels, in the acquired image leading to misinterpretation. Therefore, correcting artifacts in PAI is of importance.Previously, we proposed a method, photoacoustic-guided focused ultrasound (PAFUSion), to reduce IPAs [13,15]. This method has several limitations:...

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