A Case Study in Pharmacologic Colon Imaging Using Principal Curves in Single-Photon Emission Computed Tomography

Abstract

In this manuscript we are concerned with functional imaging of the colon to assess the kinetics of microbicide lubricants. The overarching goal is to understand the distribution of the lubricants in the colon. Such information is crucial for understanding the potential impact of the microbicide on HIV viral transmission. The experiment was conducted by imaging a radiolabeled lubricant distributed in the subject's colon. The tracer imaging was conducted via single photon emission computed tomography (SPECT), a non-invasive, in-vivo functional imaging technique. We develop a novel principal curve algorithm to construct a three dimensional curve through the colon images. The developed algorithm is tested and debugged on several difficult two-dimensional images of familiar curves where the original principal curve algorithm does not apply. The final curve fit to the colon data is compared with experimental sigmoidoscope collection.

Parameter Selection for Principal Curves

“…Roughly, the purpose is to search for a curve passing through the middle of the observations, as illustrated in Figure 1. Principal curves have a broad range of applications in many different areas, such as physics (Hastie and Stuetzle [26], Friedsam and Oren [23]), character and speech recognition (Kégl and Krzyżak [29], Reinhard and Niranjan [39]), mapping and geology (Brunsdon [10], Stanford and Raftery [43], Banfield and Raftery [4], Einbeck, Tutz and Evers [20,21]), natural sciences (De'ath [14], Corkeron, Anthony and Martin [13], Einbeck, Tutz and Evers [20]) and medicine (Wong and Chung [46], Caffo, Crainiceanu, Deng and Hendrix [11]). …”

Simultaneous Evaluation of Safety, Acceptability, Pericoital Kinetics, and Ex Vivo Pharmacodynamics Comparing Four Rectal Microbicide Vehicle Candidates

“…Participants were imaged 2, 4, and 24 h after study product dosing (Phase A and B) using a dual-head Millennium VH SPECT/CT system (GE Medical Systems, Waukesha, WI) equipped with a low-dose computed tomography (CT) unit (Hawkeye) as previously described. 20,24,26 CT images were fused with attenuation corrected SPECT images using the General Electric eN-TEGRA nuclear medicine workstation, version 1.04 (GE Medical Systems, Waukesha, WI).…”

“…Using a previously described algorithm, a flexible principal curve algorithm was used to construct a three-dimensional curve through the colon images (R version 2.13.1, The R Foundation for Statistical Computing, Vienna, Austria). 26,28,29 After the centerline was constructed, a concentration-by-distance curve was constructed based on voxel intensity within a region orthogonal to the centerline. The origin of the centerline was normalized to the coccygeal plane.…”

Quantification of the spatial distribution of rectally applied surrogates for microbicide and semen in colon with SPECT and magnetic resonance imaging

“…Principal curve algorithm to quantify the spread of surrogate After the image files containing SPECT data were read into R, the gamma signal strength of 99m Tc or 111 In were viewed in a 3-D array representing the anatomical location: sagittal (X from right to left), coronal (Y from back to front), and transverse (Z from head to foot).To construct a 3-D curve through the gamma emission signal, a novel principal curve algorithm was developed and described in detail [15]. Briefly, the three dimensional position of a curve, f, through the colon at t ʰ [0, 1] was defined by: were knots placed at equally spaced quantiles of {ti}, K + 4 was the degree of freedom of the smoother and s was the error term.…”