Photoacoustic Computed Tomography Image Research Articles

Recent advancement in transcranial brain imaging using photoacoustic computed tomography

Photoacoustic computed tomography (PACT) holds great promise for transcranial brain imaging. However, the strong reflection, scattering, and attenuation of acoustic waves by the skull present significant challenges for image reconstruction. In this talk, we will review our recent progress on transcranial PACT image reconstruction. Our contributions include the following: (1) development of a methodology to establish a discrete transcranial PACT image model by use of adjunct X-ray CT data; (2) development of image reconstruction methods that can compensate for speed-of-sound and density variations within the skull; and (3) a detailed investigation of the role of shear waves in transcranial PACT. Computer-simulated and experimental data are employed to demonstrate the feasibility of transcranial PACT.

Investigation of the far-field approximation for modeling a transducer's spatial impulse response in photoacoustic computed tomography

When ultrasonic transducers with large detecting areas and/or compact measurement geometries are employed in photoacoustic computed tomography (PACT), the spatial resolution of reconstructed images can be significantly degraded. Our goal in this work is to clarify the domain of validity of the imaging model that mitigates such effects by use of a far-field approximation. Computer-simulation studies are described that demonstrate the far-field-based imaging model is highly accurate for a practical 3D PACT imaging geometry employed in an existing small animal imaging system. For use in special cases where the far-field approximation is violated, an extension of the far-field-based imaging model is proposed that divides the transducer face into a small number of rectangular patches that are each described accurately by use of the far-field approximation.

Abstract 5224: Tracking the longitudinal physiological and vascular morphology changes in response to anti-angiogenesis treatment in breast tumors

Abstract VEGF and its receptor (VEGFR2 or flk1/KDR) play critical roles in tumor angiogenesis, which is essential for tumor growth and metastasis. The objective of this study is to track and quantify the longitudinal intra-tumor heterogeneous response to anti-VEGFR2 treatment using a combination of imaging modalities: dynamic contrast-enhanced CT (DCE-CT) and photoacoustic computed tomography (PCT). DCE-CT is used to measure vascular physiology and PCT is used to monitor its morphological changes based on its hemoglobin status within the tumor. A cohort of athymic mice bearing MCF-7VEGF (MCF-7 cells transfected with VEGF gene) tumors were divided into three groups: a control group (received non-specific, rat immunoglobulin IgG1, i.v.), a low dose therapeutic group (30 mg/kg DC101, i.v.), and a high dose therapeutic group (150 mg/kg DC101, i.v.). Twenty-four hours prior to treatment, baseline DCE-CT and PCT scans were acquired. Successive scans were taken 2 days, 1 week, and 2 weeks post treatment to track both physiological and morphological changes. For the former, a two-compartmental kinetic model is fit to contrast enhanced curves on a voxel-by-voxel basis to determine tumor physiological parameters of perfusion (F), permeability-surface area (PS), fractional plasma volume (fp) and fractional interstitial space (fis). Maximum intensity profiles (MIPs) and hemoglobin profiles were extracted from PCT images. The preliminary results show a dose dependent response to DC101 treatments. Two days post treatment, low dose reduced F by 36% and fp by 22%; high dose reduced F by 72% and fp by 39%. Tumor perfusion remained reduced two weeks post treatment, while fp in treated mice rebounded to similar levels as the control group after one week and exceeded the control group by week two. This decoupling of fp and F over time indicates a step-wise progressive nature to the formation of a vascular network and its functionality associated with the VEGF/VEGFR2 pathway. Photoacoustic results confirm the link between the changes in vascular morphology and physiology, and provide an in vivo link between vascular structure and function in response to anti-angiogenic therapy. Future work will focus on measuring the oxygen saturation levels and hemoglobin concentration in tumors by analyzing the spectroscopic information afforded by PCT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5224.

Synthesis and evaluation of near-infrared (NIR) dye-herceptin conjugates as photoacoustic computed tomography (PCT) probes for HER2 expression in breast cancer.

We are evaluating PCT imaging in conjunction with NIR dye labeled Herceptin antibody for noninvasive assessment of HER2 expression in tumors. Herceptin was labeled with Alexa Fluor-750 amine reactive dye for characterization of photoacoustic and fluorescence signals. Measurements were performed in solution and after incubation in cultured cell lines that were positive or negative in expression of HER2. The dye to antibody ratio was controlled to achieve a broad range of degree of labeling (DOL = 2 to 15). Photoacoustic signal intensity of Herceptin-dye conjugates in solution increased with increases over the entire DOL range studied. In contrast, fluorescence exhibited significant quenching for higher DOL. In vitro PCT imaging of the labeled HER2 (+) and HER2 (-) cells revealed the targeting specificity of the NIR dye labeled Herceptin. In HER2 (+) cells lines, photoacoustic signal intensity gradually increased with increasing DOL and with increasing number of cells. These results demonstrate that PCT-based measurement of HER2 receptor binding using NIR dye labeled Herceptin is feasible. The absence of a quenching effect with increased DOL advantages this method over traditional methods based on fluorescence measurement.