Takayuki Yagi

Visualization of tumor-related blood vessels in human breast by photoacoustic imaging system with a hemispherical detector array

Noninvasive measurement of the distribution and oxygenation state of hemoglobin (Hb) inside the tissue is strongly required to analyze the tumor-associated vasculatures. We developed a photoacoustic imaging (PAI) system with a hemispherical-shaped detector array (HDA). Here, we show that PAI system with HDA revealed finer vasculature, more detailed blood-vessel branching structures, and more detailed morphological vessel characteristics compared with MRI by the use of breast shape deformation of MRI to PAI and their fused image. Morphologically abnormal peritumoral blood vessel features, including centripetal photoacoustic signals and disruption or narrowing of vessel signals, were observed and intratumoral signals were detected by PAI in breast cancer tissues as a result of the clinical study of 22 malignant cases. Interestingly, it was also possible to analyze anticancer treatment-driven changes in vascular morphological features and function, such as improvement of intratumoral blood perfusion and relevant changes in intravascular hemoglobin saturation of oxygen. This clinical study indicated that PAI appears to be a promising tool for noninvasive analysis of human blood vessels and may contribute to improve cancer diagnosis.

Label-free photoacoustic imaging of human palmar vessels: a structural morphological analysis

We analysed the vascular morphology of the palm using a photoacoustic tomography (PAT) instrument with a hemispherical detector array. The three-dimensional (3D) morphology of blood vessels was determined noninvasively. Overall, 12 females and 11 males were recruited as healthy volunteers. Their ages were distributed almost evenly from 22 to 59 years. In all cases, many vascular networks were observed just beneath the skin and were determined to be veins anatomically. To analyse the major arteries, the layer containing the subcutaneous venous network was removed from the image. The analysis focused on the common and proper palmar digital arteries. We used the curvature of these arteries as a parameter to analyse their morphologies. There was no significant difference in the curvature between genders when comparing the subjects as a whole. The blood vessel curvature increased with age. Good agreement was found between the 3D numerical analysis results and the subjective evaluation of the two-dimensional (2D) projection image. The PAT system enabled visualization of the 3D features of blood vessels in the palm and noninvasive analysis of arterial tortuousness.

Development and clinical translation of photoacoustic mammography

To practically apply photoacoustic (PA) imaging technology in medicine, we have developed prototypes of a photoacoustic mammography (PAM) device to acquire images for diagnosing breast cancer in the Kyoto University/Canon joint research project (CK project supported by MEXT, Japan). First, the basic ability of the PAM system to visualize the network of blood vessels and the Hb saturation index was evaluated using a prototype of PAM that has a flat scanning detector and is capable of simultaneously acquiring photoacoustic (PA) and ultrasound images. Next, another prototype of a PAM device with hemispherical sensors was developed to improve the visibility of the 3D structure of vessels by reducing the limited view effect. In clinical examination of breast cancer cases, the PAM system allowed 3D visualization of fine vessel networks with a spatial resolution of a half-millimeter and enabled us to determine the features of tumor-related vascular structures in human breast cancer. In addition, the oxygen saturation status of Hb was visualized using two different wavelengths, enabling more precise characterization of the tumor microenvironment. Results of clinical evaluation using our developed prototype of a PAM device confirmed that PA imaging technology has the potential to promote early detection of breast cancer, and realization of its practical use is expected in the near future.

Photoacoustic imaging system visualizes restoration of peripheral oxygenation in psoriatic lesions

Photoacoustic imaging (PAI) is an emerging technology that enables visualization of vasculatures and pigmented tissue in vivo1 . PAI has been used for the detection of cancers such as melanoma, thyroid cancer and breast cancer in pre-clinical studies2,3 . To date, no study has used PAI to assess a systemic, internal disease. Many systemic diseases such as hypertension and diabetes cause atherosclerosis (a macrovascular disease) and arteriosclerosis (a microvascular disease). While atherosclerosis is readily evaluated by clinical tests such as sonographic study of the common carotid arteries, arteriosclerosis cannot be readily assessed. There is a need for modalities that can evaluate pathological changes in small vasculatures noninvasively. This article is protected by copyright. All rights reserved.

Visualising peripheral arterioles and venules through high-resolution and large-area photoacoustic imaging

Photoacoustic (PA) imaging (PAI) has been shown to be a promising tool for non-invasive blood vessel imaging. A PAI system comprising a hemispherical detector array (HDA) has been reported previously as a method providing high morphological reproducibility. However, further improvements in diagnostic capability will require improving the image quality of PAI and fusing functional and morphological imaging. Our newly developed PAI system prototype not only enhances the PA image resolution but also acquires ultrasonic (US) B-mode images at continuous positions in the same coordinate axes. In addition, the pulse-to-pulse alternating laser irradiation shortens the measurement time difference between two wavelengths. We scanned extremities and breasts in an imaging region 140u2009mm in diameter and obtained 3D-PA images of fine blood vessels, including arterioles and venules. We could estimate whether a vessel was an artery or a vein by using the S-factor obtained from the PA images at two wavelengths, which corresponds approximately to the haemoglobin oxygen saturation. Furthermore, we observed tumour-related blood vessels around breast tumours with unprecedented resolution. In the future, clinical studies with our new PAI system will help to elucidate various mechanisms of vascular-associated diseases and events.

Vascular branching point counts using photoacoustic imaging in the superficial layer of the breast: A potential biomarker for breast cancer

This study aimed to identify the characteristics of the vascular network in the superficial subcutaneous layer of the breast and to analyze differences between breasts with cancer and contralateral unaffected breasts using vessel branching points (VBPs) detected by three-dimensional photoacoustic imaging with a hemispherical detector array. In 22 patients with unilateral breast cancer, the average VBP counts to a depth of 7u202fmm below the skin surface were significantly greater in breasts with cancer than in the contralateral unaffected breasts (pu202f<u202f0.01). The ratio of the VBP count in the breasts with cancer to that in the contralateral breasts was significantly increased in patients with a high histologic grade (pu202f=u202f0.03), those with estrogen receptor-negative disease (pu202f<u202f0.01), and those with highly proliferative disease (pu202f<u202f0.01). These preliminary findings indicate that a higher number of VBPs in the superficial subcutaneous layer of the breast might be a biomarker for primary breast cancer.