Adaptive infrared patterns for microscopic surface reconstructions.

PURPOSE: Multi-zoom microscopic surface reconstructions of operating sites, especially in ENT surgeries, would allow multimodal image fusion for determining the amount of resected tissue, for recognizing critical structures, and novel tools for intraoperative quality assurance. State-of-the-art three-dimensional model creation of the surgical scene is challenged by the surgical environment, illumination, and the homogeneous structures of skin, muscle, bones, etc., that lack invariant features for stereo reconstruction. METHODS: An adaptive near-infrared pattern projector illuminates the surgical scene with optimized patterns to yield accurate dense multi-zoom stereoscopic surface reconstructions. The approach does not impact the clinical workflow. The new method is compared to state-of-the-art approaches and is validated by determining its reconstruction errors relative to a high-resolution 3D-reconstruction of CT data. RESULTS: 200 surface reconstructions were generated for 5 zoom levels with 10 reconstructions for each object illumination method (standard operating room light, microscope light, random pattern and adaptive NIR pattern). For the adaptive pattern, the surface reconstruction errors ranged from 0.5 to 0.7 mm, as compared to 1-1.9 mm for the other approaches. The local reconstruction differences are visualized in heat maps. CONCLUSION: Adaptive near-infrared (NIR) pattern projection in microscopic surgery allows dense and accurate microscopic surface reconstructions for variable zoom levels of small and homogeneous surfaces. This could potentially aid in microscopic interventions at the lateral skull base and potentially open up new possibilities for combining quantitative intraoperative surface reconstructions with preoperative radiologic imagery.

CIGuide: in situ augmented reality laser guidance.

PURPOSE : A robotic intraoperative laser guidance system with hybrid optic-magnetic tracking for skull base surgery is presented. It provides in situ augmented reality guidance for microscopic interventions at the lateral skull base with minimal mental and workload overhead on surgeons working without a monitor and dedicated pointing tools. METHODS : Three components were developed: a registration tool (Rhinospider), a hybrid magneto-optic-tracked robotic feedback control scheme and a modified robotic end-effector. Rhinospider optimizes registration of patient and preoperative CT data by excluding user errors in fiducial localization with magnetic tracking. The hybrid controller uses an integrated microscope HD camera for robotic control with a guidance beam shining on a dual plate setup avoiding magnetic field distortions. A robotic needle insertion platform (iSYS Medizintechnik GmbH, Austria) was modified to position a laser beam with high precision in a surgical scene compatible to microscopic surgery. RESULTS : System accuracy was evaluated quantitatively at various target positions on a phantom. The accuracy found is 1.2 mm ± 0.5 mm. Errors are primarily due to magnetic tracking. This application accuracy seems suitable for most surgical procedures in the lateral skull base. The system was evaluated quantitatively during a mastoidectomy of an anatomic head specimen and was judged useful by the surgeon. CONCLUSION : A hybrid robotic laser guidance system with direct visual feedback is proposed for navigated drilling and intraoperative structure localization. The system provides visual cues directly on/in the patient anatomy, reducing the standard limitations of AR visualizations like depth perception. The custom- built end-effector for the iSYS robot is transparent to using surgical microscopes and compatible with magnetic tracking. The cadaver experiment showed that guidance was accurate and that the end-effector is unobtrusive. This laser guidance has potential to aid the surgeon in finding the optimal mastoidectomy trajectory in more difficult interventions.

Platelet-Derived Growth Factor Receptor-α Regulates Proliferation of Gastrointestinal Stromal Tumor Cells With Mutations in KIT by Stabilizing ETV1.

BACKGROUND & AIMS: In gastrointestinal muscles, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) is predominantly expressed by interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor-α (PDGFRA) polypeptide is expressed by so-called fibroblast-like cells. KIT and PDGFRA have been reported to be coexpressed in ICC precursors and gastrointestinal stromal tumors (GISTs), which originate from the ICC lineage. PDGFRA signaling has been proposed to stimulate growth of GISTs that express mutant KIT, but the effects and mechanisms of selective blockade of PDGFRA are unclear. We investigated whether inhibiting PDGFRA could reduce proliferation of GIST cells with mutant KIT via effects on the KIT-dependent transcription factor ETV1. METHODS: We studied 53 gastric, small intestinal, rectal, or abdominal GISTs collected immediately after surgery or archived as fixed blocks at the Mayo Clinic and University of California, San Diego. In human GIST cells carrying imatinib-sensitive and imatinib-resistant mutations in KIT, PDGFRA was reduced by RNA interference (knockdown) or inhibited with crenolanib besylate (a selective inhibitor of PDGFRA and PDGFRB). Mouse ICC precursors were retrovirally transduced to overexpress wild-type Kit. Cell proliferation was analyzed by methyltetrazolium, 5-ethynyl-2'-deoxyuridine incorporation, and Ki-67 immunofluorescence assays; we also analyzed growth of xenograft tumors in mice. Gastric ICC and ICC precursors, and their PDGFRA(+) subsets, were analyzed by flow cytometry and immunohistochemistry in wild-type, Kit(+/copGFP), Pdgfra(+/eGFP), and NOD/ShiLtJ mice. Immunoblots were used to quantify protein expression and phosphorylation. RESULTS: KIT and PDGFRA were coexpressed in 3%-5% of mouse ICC, 35%-44% of ICC precursors, and most human GIST samples and cell lines. PDGFRA knockdown or inhibition with crenolanib efficiently reduced proliferation of imatinib-sensitive and imatinib-resistant KIT(+)ETV1(+)PDGFRA(+) GIST cells (50% maximal inhibitory concentration = 5-32 nM), but not of cells lacking KIT, ETV1, or PDGFRA (50% maximal inhibitory concentration >230 nM). Crenolanib inhibited phosphorylation of PDGFRA and PDGFRB, but not KIT. However, Kit overexpression sensitized mouse ICC precursors to crenolanib. ETV1 knockdown reduced KIT expression and GIST proliferation. Crenolanib down-regulated ETV1 by inhibiting extracellular-signal-regulated kinase (ERK)-dependent stabilization of ETV1 protein and also reduced expression of KIT and PDGFRA. CONCLUSIONS: In KIT-mutant GIST, inhibition of PDGFRA disrupts a KIT-ERK-ETV1-KIT signaling loop by inhibiting ERK activation. The PDGFRA inhibitor crenolanib might be used to treat patients with imatinib-resistant, KIT-mutant GIST.