d Original Contribution CONTRAST-ULTRASOUND DISPERSION IMAGING FOR PROSTATE CANCER LOCALIZATION BY IMPROVED SPATIOTEMPORAL SIMILARITYANALYSIS M. P. J. KUENEN,* y T. A. SAIDOV ,* H. WIJKSTRA,* y and M. MISCHI* *Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; and y Department of Urology, Academic Medical Center University Hospital, Amsterdam, The Netherlands (Received 21 February 2012; revised 18 January 2013; in final form 5 March 2013) Abstract—Angiogenesis plays a major role in prostate cancer growth. Despite extensive research on blood perfu- sion imaging aimed at angiogenesis detection, the diagnosis of prostate cancer still requires systematic biopsies. This may be due to the complex relationship between angiogenesis and microvascular perfusion. Analysis of ultrasound-contrast-agent dispersion kinetics, determined by multipath trajectories in the microcirculation, may provide better characterization of the microvascular architecture. We propose the physical rationale for dispersion estimation by an existing spatiotemporal similarity analysis. After an intravenous ultrasound- contrast-agent bolus injection, dispersion is estimated by coherence analysis among time-intensity curves measured at neighbor pixels. The accuracy of the method is increased by time-domain windowing and anisotropic spatial filtering for speckle regularization. The results in 12 patient data sets indicated superior agreement with histology (receiver operating characteristic curve area 5 0.88) compared with those obtained by reported perfu- sion and dispersion analyses, providing a valuable contribution to prostate cancer localization. (E-mail: m.p.j. kuenen@tue.nl) Ó 2013 World Federation for Ultrasound in Medicine & Biology. Key Words: Ultrasound contrast agents, Angiogenesis, Microcirculation, Prostate cancer. INTRODUCTION Prostate cancer is the most common form of cancer in men in the United States, representing 29% and 9% of all cancer diagnoses and deaths, respectively (American Cancer Society 2012). Treatment often involves a radical prostatectomy, which carries the risk of severe permanent side effects like incontinence and impotence (Bangma et al. 2007). This risk could be reduced by focal therapies (Polascik and Mouraviev 2008), but their use is compli- cated by diagnostic limitations. In fact, diagnosis requires systematic biopsies, in which the prostate is uniformly sampled up to more than 16 times by a core needle. Imaging methods could significantly improve the current situation by enabling better patient stratification, biopsy targeting and focal therapy guidance, but are not yet available. Angiogenesis is a key prognostic indicator for pros- tate cancer imaging, especially because of its correlation with cancer aggressiveness and the risk of developing metastasis (Brawer 1996; Weidner et al. 1993). This biochemical process leads to the formation of a dense microvascular network supporting the growth of prostate cancer beyond 1 mm 3 (Brawer 1996). Differences in the microvascular architecture are characterized by an increased microvascular density as well as a higher tortu- osity and permeability of the vessel wall (Bigler et al. 1993). Detection of angiogenesis by assessment of tissue perfusion using techniques such as dynamic contrast- enhanced magnetic resonance imaging (DCE-MRI), Doppler ultrasound imaging and dynamic contrast- enhanced ultrasound (DCE-US) imaging has been proposed (Russo et al. 2012; Seitz et al. 2009; Smeenge et al. 2011). Given its use in biopsy guidance and its real-time availability at the bedside, ultrasound offers a practical and cost-effective alternative to magnetic reso- nance imaging for prostate imaging. Dynamic contrast-enhanced ultrasound is especially interesting because of its ability to obtain flow informa- tion from within the smallest microvessels. The adopted ultrasound contrast agents (UCAs) are coated gas micro- bubbles. Because they are comparable in size to red blood cells, these microbubbles can flow into the smallest Address correspondence to: M. P. J. Kuenen, Department of Elec- trical Engineering, Eindhoven University of Technology, Den Dolech 2, 5600 MB Eindhoven, The Netherlands. E-mail: m.p.j.kuenen@tue.nl 1 Ultrasound in Med. & Biol., Vol. -, No. -, pp. 1–11, 2013 Copyright Ó 2013 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/$ - see front matter http://dx.doi.org/10.1016/j.ultrasmedbio.2013.03.004