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Clinical trials with novel fluorescence contrast agents for head and neck cancer are driving new applications for fluorescence-guided surgery. Two-dimensional fluorescence imaging systems, however, provide limited in vivo assessment capabilities to determine tumor invasion depth below the mucosal surface. Here, we investigate the use of spatial frequency domain imaging (SFDI) methods for sub-surface fluorescence in tissue-simulating oral cancer phantoms. A two-step profile-correction approach for SFDI is under development to account for the complex surface topography of the oral cavity. First, for structured-illumination estimation of the surface profile, we are evaluating gray code and phase shift profilometry methods in agar-based oral cavity phantoms to maximize resolution and minimize sensitivity to surface discontinuities. Second, for profile-correction of the diffuse reflectance, global lighting effects within the oral cavity – analogous to an integrating sphere – are modeled using a multi-bounce numerical model. Subsurface fluorescence imaging is enabled based on the variations in optical sampling depth that result from changes in spatial frequency. An analytical depth recovery approach is based on a numerical diffusion theory model for semi-infinite fluorescence slabs of variable thickness. Depth estimation is evaluated in an agar-based phantom with fluorescence inclusions of thicknesses 1-5.5 mm originating from the top surface (“iceberg model”). Future clinical studies are necessary to assess in vivo performance and intraoperative workflow.

Current intraoperative methods to assess tumor invasion depth in mucosal oral cancer provide limited real-time information. The advent of targeted fluorescence contrast agents for head and neck cancer is a promising innovation, but surgical imaging systems typically provide only two-dimensional views. Here, we investigate the use of an image-guided fluorescence tomography (igFT) system to estimate the depth of tumor invasion in tissue-simulating oral cancer phantoms. Implementation of non-contact diffuse optical tomography using finite-element software (NIRFAST) is enabled with geometric data from intraoperative cone-beam CT (CBCT) imaging and surgical navigation. The tissue phantoms used gelatin for the background (5% for fat, 10% for muscle) and 2% agar for palpable, tumor-like inclusions. Standard agents were used for absorption (hemoglobin), scattering (Intralipid), fluorescence (indocyanine green), and CT contrast (iohexol). The agar inclusions were formed using 3D printed molds, and positioned at the surface of the gelatin background to mimic mucosal tumor invasion (an “iceberg” model). Simulations and phantom experiments characterize fluorescence tomography performance across a range of tumor invasion depths. To aid surgical visualization, the fluorescence volume is converted to a colored surface indicating tumor depth, and overlaid on the navigated endoscopic video. Clinical studies are necessary to assess in vivo performance and intraoperative workflow.

Intraoperative visualization of molecular processes delineated by fluorescence contrast agents offers the potential for increased surgical precision and better patient outcomes. To exploit fully the clinical potential for targeted fluorescence guidance, there is a growing need to develop high-resolution, quantitative imaging systems suitable for surgical use. Diffuse optical fluorescence tomography (DOFT) systems in pre-clinical and diagnostic imaging applications have demonstrated improvements in fluorescence quantification with the addition of a priori data from structural imaging modalities (e.g., MR, CT). Here, we investigate the use of a cone-beam CT (CBCT) surgical guidance system to generate spatial priors for intraoperative DOFT. Imaging and localization data is incorporated directly into a finite element method DOFT implementation (NIRFAST) at multiple stages. First, CBCT data from an intraoperative flat-panel C-arm is used to generate tetrahedral meshes. Second, optical tracking of laser and camera devices enables an adaptable non-contact DOFT approach to accommodate various anatomical sites and acquisition geometries. Finally, anatomical segmentations from CBCT are included in the optical reconstruction process using Laplacian-type regularization (“soft spatial priors”). Calibration results showed that light rays between the tissue surface and navigated optical devices were mapped with sub-millimeter accuracy. Liquid phantom experiments determined the improvements in quantification of fluorescence yield, with errors of 85% and

A freehand, non-contact diffuse optical tomography (DOT) system has been developed for multimodal imaging with intraoperative cone-beam CT (CBCT) during minimally-invasive cancer surgery. The DOT system is configured for near-infrared fluorescence imaging with indocyanine green (ICG) using a collimated 780 nm laser diode and a nearinfrared CCD camera (PCO Pixelfly USB). Depending on the intended surgical application, the camera is coupled to either a rigid 10 mm diameter endoscope (Karl Storz) or a 25 mm focal length lens (Edmund Optics). A prototype flatpanel CBCT C-Arm (Siemens Healthcare) acquires low-dose 3D images with sub-mm spatial resolution. A 3D mesh is extracted from CBCT for finite-element DOT implementation in NIRFAST (Dartmouth College), with the capability for soft/hard imaging priors (e.g., segmented lymph nodes). A stereoscopic optical camera (NDI Polaris) provides real-time 6D localization of reflective spheres mounted to the laser and camera. Camera calibration combined with tracking data is used to estimate intrinsic (focal length, principal point, non-linear distortion) and extrinsic (translation, rotation) lens parameters. Source/detector boundary data is computed from the tracked laser/camera positions using radiometry models. Target registration errors (TRE) between real and projected boundary points are ~1-2 mm for typical acquisition geometries. Pre-clinical studies using tissue phantoms are presented to characterize 3D imaging performance. This translational research system is under investigation for clinical applications in head-and-neck surgery including oral cavity tumour resection, lymph node mapping, and free-flap perforator assessment.

A prototype mobile C-arm for cone-beam CT (CBCT) has been translated to a prospective clinical trial in head and neck surgery. The flat-panel CBCT C-arm was developed in collaboration with Siemens Healthcare, and demonstrates both sub-mm spatial resolution and soft-tissue visibility at low radiation dose (e.g.

High-quality intraoperative 3D imaging systems such as cone-beam CT (CBCT) hold considerable promise for imageguided surgical procedures in the head and neck. With a large amount of preoperative imaging and planning information available in addition to the intraoperative images, it becomes desirable to be able to integrate all sources of imaging information within the same anatomical frame of reference using deformable image registration. Fast intensity-based algorithms are available which can perform deformable image registration within a period of time short enough for intraoperative use. However, CBCT images often contain voxel intensity inaccuracy which can hinder registration accuracy - for example, due to x-ray scatter, truncation, and/or erroneous scaling normalization within the 3D reconstruction algorithm. In this work, we present a method of integrating an iterative intensity matching step within the operation of a multi-scale Demons registration algorithm. Registration accuracy was evaluated in a cadaver model and showed that a conventional Demons implementation (with either no intensity match or a single histogram match) introduced anatomical distortion and degradation in target registration error (TRE). The iterative intensity matching procedure, on the other hand, provided robust registration across a broad range of intensity inaccuracies.

Methods for accurate registration and fusion of intraoperative cone-beam CT (CBCT) with endoscopic video have been developed and integrated into a system for surgical guidance that accounts for intraoperative anatomical deformation and tissue excision. The system is based on a prototype mobile C-Arm for intraoperative CBCT that provides low-dose 3D image updates on demand with sub-mm spatial resolution and soft-tissue visibility, and also incorporates subsystems for real-time tracking and navigation, video endoscopy, deformable image registration of preoperative images and surgical plans, and 3D visualization software. The position and pose of the endoscope are geometrically registered to 3D CBCT images by way of real-time optical tracking (NDI Polaris) for rigid endoscopes (e.g., head and neck surgery), and electromagnetic tracking (NDI Aurora) for flexible endoscopes (e.g., bronchoscopes, colonoscopes). The intrinsic (focal length, principal point, non-linear distortion) and extrinsic (translation, rotation) parameters of the endoscopic camera are calibrated from images of a planar calibration checkerboard (2.5×2.5 mm2 squares) obtained at different perspectives. Video-CBCT registration enables a variety of 3D visualization options (e.g., oblique CBCT slices at the endoscope tip, augmentation of video with CBCT images and planning data, virtual reality representations of CBCT [surface renderings]), which can reveal anatomical structures not directly visible in the endoscopic view - e.g., critical structures obscured by blood or behind the visible anatomical surface. Video-CBCT fusion is evaluated in pre-clinical sinus and skull base surgical experiments, and is currently being incorporated into an ongoing prospective clinical trial in CBCT-guided head and neck surgery.

esthetic appearance is one of the most important factors for reconstructive surgery. The current practice of maxillary reconstruction chooses radial forearm, fibula or iliac rest osteocutaneous to recreate three-dimensional complex structures of the palate and maxilla. However, these bone flaps lack shape similarity to the palate and result in a less satisfactory esthetic. Considering similarity factors and vasculature advantages, reconstructive surgeons recently explored the use of scapular tip myo-osseous free flaps to restore the excised site. We have developed a new method that quantitatively evaluates the morphological similarity of the scapula tip bone and palate based on a diagnostic volumetric computed tomography (CT) image. This quantitative result was further interpreted as a color map that rendered on the surface of a three-dimensional computer model. For surgical planning, this color interpretation could potentially assist the surgeon to maximize the orientation of the bone flaps for best fit of the reconstruction site. With approval from the Research Ethics Board (REB) of the University Health Network, we conducted a retrospective analysis with CT image obtained from 10 patients. Each patient had a CT scans including the maxilla and chest on the same day. Based on this image set, we simulated total, subtotal and hemi palate reconstruction. The procedure of simulation included volume segmentation, conversing the segmented volume to a stereo lithography (STL) model, manual registration, computation of minimum geometric distances and curvature between STL model. Across the 10 patients data, we found the overall root-mean-square (RMS) conformance was 3.71± 0.16 mm

Surgical simulation has become a critical component of surgical practice and training in the era of high-precision image-guided surgery. While the ability to simulate surgery of the paranasal sinuses and skull base has been conventionally limited to 3D digital simulation or cadaveric dissection, we have developed novel methods employing rapid prototyping technology and 3D printing to create high-fidelity models from real patient images (CT or MR). Such advances allow creation of patient-specific models for preparation, simulation, and training before embarking on the actual surgery. A major challenge included the development of novel material formulations compatible with the rapid prototyping process while presenting anatomically realistic flexibility, cut-ability, drilling purchase, and density (CT number). Initial studies have yielded realistic models of the paranasal sinuses and skull base for simulation and training in image-guided surgery. The process of model development and material selection is reviewed along with the application of the phantoms in studies of high-precision surgery guided by C-arm cone-beam CT (CBCT). Surgical performance is quantitatively evaluated under CBCT guidance, with the high-fidelity phantoms providing an excellent test-bed for reproducible studies across a broad spectrum of challenging surgical tasks. Future work will broaden the atlas of models to include normal anatomical variations as well as a broad spectrum of benign and malignant disease. The role of high-fidelity models produced by rapid prototyping is discussed in the context of patient-specific case simulation, novel technology development (specifically CBCT guidance), and training of future generations of sinus and skull base surgeons.

A system for intraoperative cone-beam CT (CBCT) surgical guidance is under development and translation to trials in head and neck surgery. The system provides 3D image updates on demand with sub-millimeter spatial resolution and soft-tissue visibility at low radiation dose, thus overcoming conventional limitations associated with preoperative imaging alone. A prototype mobile C-arm provides the imaging platform, which has been integrated with several novel subsystems for streamlined implementation in the OR, including: real-time tracking of surgical instruments and endoscopy (with automatic registration of image and world reference frames); fast 3D deformable image registration (a newly developed multi-scale Demons algorithm); 3D planning and definition of target and normal structures; and registration / visualization of intraoperative CBCT with the surgical plan, preoperative images, and endoscopic video. Quantitative evaluation of surgical performance demonstrates a significant advantage in achieving complete tumor excision in challenging sinus and skull base ablation tasks. The ability to visualize the surgical plan in the context of intraoperative image data delineating residual tumor and neighboring critical structures presents a significant advantage to surgical performance and evaluation of the surgical product. The system has been translated to a prospective trial involving 12 patients undergoing head and neck surgery - the first implementation of the research prototype in the clinical setting. The trial demonstrates the value of high-performance intraoperative 3D imaging and provides a valuable basis for human factors analysis and workflow studies that will greatly augment streamlined implementation of such systems in complex OR environments.

High-performance intraoperative imaging is essential to an ever-expanding scope of therapeutic procedures ranging from tumor surgery to interventional radiology. The need for precise visualization of bony and soft-tissue structures with minimal obstruction to the therapy setup presents challenges and opportunities in the development of novel imaging technologies specifically for image-guided procedures. Over the past ~5 years, a mobile C-arm has been modified in collaboration with Siemens Medical Solutions for 3D imaging. Based upon a Siemens PowerMobil, the device includes: a flat-panel detector (Varian PaxScan 4030CB); a motorized orbit; a system for geometric calibration; integration with real-time tracking and navigation (NDI Polaris); and a computer control system for multi-mode fluoroscopy, tomosynthesis, and cone-beam CT. Investigation of 3D imaging performance (noise-equivalent quanta), image quality (human observer studies), and image artifacts (scatter, truncation, and cone-beam artifacts) has driven the development of imaging techniques appropriate to a host of image-guided interventions. Multi-mode functionality presents a valuable spectrum of acquisition techniques: i.) fluoroscopy for real-time 2D guidance; ii.) limited-angle tomosynthesis for fast 3D imaging (e.g., ~10 sec acquisition of coronal slices containing the surgical target); and iii.) fully 3D cone-beam CT (e.g., ~30-60 sec acquisition providing bony and soft-tissue visualization across the field of view). Phantom and cadaver studies clearly indicate the potential for improved surgical performance - up to a factor of 2 increase in challenging surgical target excisions. The C-arm system is currently being deployed in patient protocols ranging from brachytherapy to chest, breast, spine, and head and neck surgery.

A promising imaging platform for combined low-dose fluoroscopy and cone-beam CT (CBCT) guidance ofinterventional procedures hasbeen developed in our laboratory. Based on a mobile isocentric C-arm (SiemensPowerMobil) incorporating a high-performance flat-panel detector (Varian PaxScan 4030CB), the system demonstratessub-mm 3D spatial resolution and soft-tissue vi sibility with field of view sufficient for head and body sites. For pre-clinical studies in head neck tumor su rgery, we hypothesize th at the 3D intraoperative info rmation provided by CBCTpermits precise, aggressive techniques with improved avoidance of critical structures. The objectives include: 1) quantify improvement in surgical performance achieved with CBCT guidance compared to open and endoscopictechniques; and 2) investigate specific, ch allenging surgical tasks under CBCT gui dance. Investigations proceed from anidealized phantom model to cadaveric specimens. A novel sur gical performance evaluation method based on statisticaldecision theory is applied to excision and avoidance tasks. Analogous to receiver operating characteristic (ROC) analysis in medical imaging, the method quantifies surgical performance in terms of Lesion-Excised (True-Positve),Lesion-Remaining (False-Negative), Normal-Excised (False-Positive), and Normal-Remaining (True-Negative)fractions. Conservative and aggressive excision and avoidance tasks are executed in 12 cadaveric specimens with and without CBCT guidance, including: dissecti on through dura, preservation of po sterior lamina, ethmoid air cells removal,exposure of peri-orbita, and excision of infiltrated bone in the skull base (cli vus). Intraoperative CBCT data was foundto dramatically improve surgical performance and confidence in the execution of such tasks. Pre-clinical investigation ofthis platform in head and neck surgery, as well as spinal, trauma, biopsy, and other non vascular procedures, is discussed.Keywords: cone-beam CT, fluoroscopy, flat-panel detector, imaging performance, 3D imaging, image-guided surgery,image-guided interven tions, head and neck surgery, C-arm, surgical performance, image guidance, endoscopy