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ObjectivesIn mouse models of pancreatic cancer, IPI-926, an oral Hedgehog inhibitor, increases chemotherapy delivery by depleting tumor-associated stroma. This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with advanced pancreatic cancer.MethodsPatients were treated with once-daily IPI-926 plus FOLFIRINOX. A 3 + 3 dose escalation design was used, with cohort expansion at the maximum tolerated dose. A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion.ResultsThe maximum tolerated dose was identified 1 dose level below standard FOLFIRINOX. Common treatment-related adverse events included liver function test abnormalities, neuropathy, nausea/vomiting, and diarrhea. Objective response rate was high (67%), and patients receiving IPI-926 maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination.ConclusionsThis is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design. Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen, future development of Hedgehog inhibitors in pancreatic cancer seems unlikely.

Three-dimensional (3-D) localization of individual cochlear implant electrodes within the inner ear is of importance for modeling the electrical field of the cochlea, designing the electrode array, and programming the associated speech processor. A 3-D reconstruction method of cochlear implant electrodes is proposed to localize individual electrodes from two X-ray views in combination with the spiral computed tomography technique. By adapting epipolar geometry to the configuration of an X-ray imaging system, we estimate individual electrode locations in the least square sense without using a patient attachment required by an existing stereophotogrammetry technique. Furthermore, our method does not require any knowledge of the intrinsic and extrinsic parameters of the imaging system. The performance of our method is studied in numerical simulation and with patient data and is found to be sufficiently accurate for clinical use. The maximum root mean-square errors measured are 0.0445 and 0.214 mm for numerical simulation and patient data, respectively. Index Terms--Cochlear implantation, epipolar geometry, spiral computed tomography, three-dimensional (3-D) localization of individual implant electrodes, x-ray stereophotogrammetry.

To discriminate fine anatomical features in the inner ear, it has been desirable that spiral computed tomography (CT) may perform beyond their current resolution limits with the aid of digital image processing techniques. In this paper, we develop a blind deblurring approach to enhance image resolution retrospectively without complete knowledge of the underlying point spread function (PSF). An oblique CT image can be approximated as the convolution of an isotropic Gaussian PSF and the actual cross section. Practically, the parameter of the PSF is often unavailable. Hence, estimation of the parameter for the underlying PSF is crucially important for blind image deblurring. Based on the iterative deblurring theory, we formulate an edge-to-noise ratio (ENR) to characterize the image quality change due to deblurring. Our blind deblurring algorithm estimates the parameter of the PSF by maximizing the ENR, and deblurs images. In the phantom studies, the blind deblurring algorithm reduces image blurring by about 24%, according to our blurring residual measure. Also, the blind deblurring algorithm works well in patient studies. After fully automatic blind deblurring, the conspicuity of the submillimeter features of the cochlea is substantially improved. Index Terms--Blind deblurring/deconvolution, cochlear implantation, computed tomography (CT), edge-to-noise ratio (ENR), EM algorithm, Gaussian blurring, spiral/helical CT.

X-ray computed tomography fluoroscopy (CTF) enables image guidance of interventions, synchronization of scanning with contrast bolus arrival, and motion analysis. However, filtered backprojection (FB), the current method for CTF image reconstruction, is subject to motion and metal artifacts from implants, needles, or other surgical instruments. Reduced target lesion conspicuity may result from increased image noise associated with reduced tube current. In this report, we adapt the row-action expectation-maximization (EM) algorithm for CTF. Because time-dependent variation in images is localized during CTF, the row-action EM-like algorithm allows rapid convergence. More importantly, this iterative CTF algorithm has fewer metal artifacts and better low-contrast performance than FB. Index Terms - Filtered backprojection (FB), image noise, low-contrast resolution, metal artifacts, motion artifacts, row-action expectation maximization (EM), X-ray computed tomography fluoroscopy (CTF).

Gastrointestinal (GI) tract examination with spiral/helical computed tomography (CT) is currently performed by slice-based inspection of axial images. CT colography is a recent advance which allows an intraluminal visualization of the colon, similar to endoscopy. Various rendering algorithms have been developed with promising results, however navigation through the complex, tortuous anatomy of the colon can be time consuming in practice. In this paper, we propose an electrical-field-based method to unravel the convoluted colon, that is, to digitally straighten it with curved cross sections and flatten it over a plane. In our method, electrical charges are simulated along the central colon path. Curved cross sections are defined by the electrical force lines, and lead to consistent unraveling. It is demonstrated with image volumes of two patients that this technique produces a global planar view of complicated colon features with a potential for detection of polyps. Index Terms - Computed tomography (CT), spiral/helical CT, colography, unraveling.

Cochlear implantation is the standard treatment for profound hearing loss. Preimplantation and postimplantation spiral computed tomography (CT) is essential in several key clinical and research aspects. The maximum image resolution with commercial spiral CT scanners is insufficient to define clearly anatomical features and implant electrode positions in the inner ear. In this paper, we develop an expectation-maximization (EM)-like iterative deblurring algorithm to achieve spiral CT image super-resolution for cochlear implantation, assuming a spatially invariant linear spiral CT system with a three-dimensional (3-D) separable Gaussian point spread function (PSF). We experimentally validate the 3-D Gaussian blurring model via phantom measurement and profile fitting. The imaging process is further expressed as convolution of an isotropic 3-D Gaussian PSF and a blurred underlying volumetric image. Under practical conditions, an oblique reconstructed section is approximated as convolution of an isotropic two-dimensional (2-D) Gaussian PSF and the corresponding actual cross section. The spiral CT image deblurring algorithm is formulated with sieve and resolution kernels for suppressing noise and edge artifacts. A typical cochlear cross section is used for evaluation, demonstrating a resolution gain up to 30%-40% according to the correlation criterion. Physical phantoms, preimplantation and postimplantation patients are reconstructed into volumes of 0.1-mm cubic voxels. The patient images are digitally unwrapped along the central axis of the cochlea and the implanted electrode array respectively, then oblique sections orthogonal to the central axis formed. After deblurring, representation of structural features is substantially improved in all the cases. Index Terms - Cochlear implantation, computed tomography (CT), spiral/helical CT, deblurring, deconvolution.