Date Published: February 23, 2017
Publisher: Public Library of Science
Author(s): Guan Xu, Yafang Xue, Zeynep Gürsel Özkurt, Naziha Slimani, Zizhong Hu, Xueding Wang, Kewen Xia, Teng Ma, Qifa Zhou, Hakan Demirci, Heye Zhang.
The purpose of this study is to examine the capability of photoacoustic (PA) imaging (PAI) in assessing the unique molecular and architectural features in ocular tumors. A real-time PA and ultrasonography (US) parallel imaging system based on a research US platform was developed to examine retinoblastoma in mice in vivo and human retinoblastoma and uveal melanoma ex vivo. PA signals were generated by optical illumination at 720, 750, 800, 850, 900 and 950 nm delivered through a fiber optical bundle. The optical absorption spectra of the tumors were derived from the PA images. The optical absorption spectrum of each tumor was quantified by fitting to a polynomial model. The microscopic architectures of the tumors were quantified by frequency domain analysis of the PA signals. Both the optical spectral and architectural features agree with the histological findings of the tumors. The mouse and human retinoblastoma showed comparable total optical absorption spectra at a correlation of 0.95 (p<0.005). The quantitative PAI features of human retinoblastoma and uveal melanoma have shown statistically significant difference in two tailed t-tests (p<0.05). Fully compatible with the concurrent procedures, PAI could be a potential tool complementary to other diagnostic modalities for characterizing intraocular tumors.
Intraocular tumors have relatively low incidence but could be life-threatening if not diagnosed or treated appropriately [1, 2]. The diagnosis of intraocular tumors mainly relies on the structural information and the clinical examination provided by non-invasive imaging technologies [3, 4]. However, the current imaging techniques lack to provide any detail about the histopathologic structure or functional information. Ultrasound (US) imaging, optical coherence tomography and fluorescein angiography are most commonly used diagnostic tests. US, taking advantage of the acoustic transparency of biological tissues, provides information about the shape, dimensions, location, and intrinsic structure of intraocular tumors [5, 6]. The mono-physics nature of US measurements let evaluate only the physical parameters of the backscatters in tissues such as dimensions and tissue densities without interrogating the molecular components forming these backscatters. Fluorescein angiography visualizes the vasculature in superficial structures such as the iris, retina and choroid by introducing exogenous contrast agents [7, 8]. Optical coherence tomography [9, 10] can provide a detailed structural mapping of retinal layer but limited resolution in the deeper choroidal layer , affected by the strong optical scattering property of biological tissues . Although these techniques are helpful in the diagnosis of most intraocular tumors, atypical cases continue to be challenging. An imaging technique that can assess the molecular components and corresponding architectures inside an intraocular tumor will be helpful, important and innovative in the differential diagnosis.
The data acquisition and analysis approaches in our previous study  were used in part of this study.
Experiment data in addition to those presented in  were acquired. The data were thoroughly analyzed. More solid conclusions were achieved.
PAI is a hybrid modality that combines the sensitivity and contrast of optical imaging with the depth and resolution of US. US and PA image shows complementary information by using different contrast mechanisms. In US, the imaging of eye and intraocular tumor represents ultrasonic backscattering due to acoustic impedance mismatch at the interfaces of tissue structures. Retinoblastoma has heterogeneous histopathological architectures due to necrosis and calcification which are shown in US images as hyperechoic areas. Uveal melanoma has relatively homogeneous histopathological architecture with rich melanin content. The uniform internal structure in melanoma leads to a hypoechoic mass in US. In PAI, both tumors show positive contrasts over the background as a result of their strong optical absorption. The spectroscopic optical absorption profiles reflect the dominant molecular components in the tumors. For instance, the optical absorption spectra of retinoblastoma descend much faster than those of uveal melanoma in the 700–950 nm range in Fig 5, which agrees with the optical absorption spectra of calcium and melanin shown in Fig 2.
In summary, this is the first study that shows the feasibility of assessing intraocular tumors with PAI. A PA-US parallel imaging system and data processing techniques were developed to reveal the unique tissue optical absorption spectra and microscopic architectures of retinoblastoma and uveal melanoma. Such imaging modality may play an important role in differential diagnosis of intraocular tumors.