Intraoperative cone-beam CT spatial priors for diffuse optical fluorescence tomography.

A hybrid system for intraoperative cone-beam CT (CBCT) imaging and continuous-wave fluorescence tomography (FT) has been developed using an image-guidance framework. Intraoperative CBCT images with sub-millimeter spatial resolution are acquired with a flat-panel C-Arm. Tetrahedral meshes are generated from CBCT for finite element method implementation of diffuse optical tomography (NIRFAST). Structural data from CBCT is incorporated directly into the optical reconstruction process using Laplacian-type regularization ('soft spatial priors'). Experiments were performed using an in-house optical system designed for indocyanine green (ICG) fluorescence. A dynamic non-contact geometry was achieved using a stereoscopic optical tracker for real-time localization of a laser diode and CCD camera. Source and detector positions were projected onto the boundary elements of the tissue mesh using algorithms for ray-triangle intersection and camera lens calibration. Simulation studies showed the capabilities of a soft-prior approach, even in the presence of segmentation uncertainties. Experiments with ICG targets embedded in liquid phantoms determined the improvements in the quantification of the fluorophore yield, with errors of 85% and <20% for no priors and spatial priors, respectively. Similar results were observed with the ICG target embedded in ex vivo porcine loin, with errors of 52% and 12%, respectively. A proof-of-principal animal study was performed in a VX2-tumor in vivo rabbit model using liposomal nanoparticles co-encapsulating contrast for CT (iohexol) and fluorescence (ICG) imaging. Fusion of CBCT and FT reconstructions demonstrated concurrent anatomical and functional delineations of contrast enhancement around the periphery of the buccal tumor. These developments motivate future clinical translation of the FT system into an ongoing CBCT-guided head and neck surgery trial.

Navigated non-contact fluorescence tomography.

A non-contact approach for diffuse optical tomography (DOT) has been developed for on-demand image updates using surgical navigation technology. A stereoscopic optical tracker provides real-time localization of reflective spheres mounted to a laser diode and near-infrared camera. Standard camera calibration is combined with tracking data to determine the intrinsic camera parameters (focal length, principal point and non-linear lens distortion) and the tracker-to-camera transform. Tracker-to-laser calibration is performed using images of laser beam intersection with a tracked calibration surface. Source and detector positions for a finite-element DOT implementation are projected onto the boundary elements of the tissue mesh by finding ray-triangle intersections. A multi-stage model converts camera counts to surface flux by accounting for lens aperture settings, fluorescence filter transmittance, photodetector quantum efficiency, photon energy, exposure time, readout offset and camera gain. The image-guidance framework was applied to an in-house optical tomography system configured for indocyanine green (ICG) fluorescence. Mean target registration errors for camera and laser calibration were less than 1 mm. Surface flux measurements of total reflectance and fluorescence in Intralipid-based fluorescence phantoms (0-2 µg ml-1) had mean errors of 3.1% and 4.4%, respectively, relative to diffusion theory predictions. Spatially-resolved reflectance measurements in a calibrated optical phantom agreed with theory for radial distances up to 25 mm from the laser source. Inverse fluorescence reconstructions of a sub-surface fluorescence target confirmed the localization accuracy (average target centroid error of 0.44 mm). This translational research system is under investigation for clinical applications in head and neck surgery, including oral cavity tumor resection, lymph node mapping and free-flap perforator assessment.

The effects of electrode misplacement on clinicians' interpretation of the standard 12-lead electrocardiogram.

INTRODUCTION: This study investigates how a particular incorrect electrode configuration affects the 12-lead Electrocardiogram (ECG). METHODS: A correct and an incorrect 12-lead ECG were extracted from a 192-lead BSPM. This was done for 232 BSPMs yielding 464 12-lead ECGs. The particular incorrect ECG involved displacing electrodes V1 and V2 in the second intercostal space whilst also offsetting the remaining electrodes. These ECGs were examined in two stages: (a) analysis of the effects of electrode misplacement on signal morphology and (b) analysis of how often the incorrect electrode configuration changed the diagnosis of two clinicians in a random sample of 75 patients. RESULTS: According to the Root Mean Square Error (RMSE) of the difference between PQRST intervals in the correct and incorrect ECGs, lead V2 is the most affected lead (mean: 185 µV ± 82 µV), followed by lead V4 (mean: 114 µV ± 59 µV) and lead V1 (mean: 100 µV ± 47 µV). It was found that if the incorrect electrode configuration is applied, there is a 17% to a 24% chance the diagnostic interpretation will be different. Quantified using Similarity Coefficient (SC) leads V1 and V2 were found to be more alike when misplaced in the second intercostal space. The average SC between these leads when correctly placed was 0.08 (± 0.65), however when incorrectly placed, the average SC was 0.43 (± 0.3). CONCLUSION: There is a reasonable chance this particular incorrect electrode configuration will change the diagnosis of the 12-lead ECG. This highlights the importance of developing algorithms to detect electrode misplacement along with better education regarding ECG acquisition.

Improving superficial target delineation in radiation therapy with endoscopic tracking and registration.

PURPOSE: Target delineation within volumetric imaging is a critical step in the planning process of intensity modulated radiation therapy. In endoluminal cancers, endoscopy often reveals superficial areas of visible disease beyond what is seen on volumetric imaging. Quantitatively relating these findings to the volumetric imaging is prone to human error during the recall and contouring of the target. We have developed a method to improve target delineation in the radiation therapy planning process by quantitatively registering endoscopic findings contours traced on endoscopic images to volumetric imaging. METHODS: Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were registered to computed tomography (CT) volumetric images by tracking the position and orientation of the endoscope relative to a CT image set. Regions-of-interest (ROI) in the 2D endoscopic view were delineated. A mesh created within the boundary of the ROI was projected onto the 3D image data, registering the ROI with the volumetric image. This 3D ROI was exported to clinical radiation treatment planning software. The precision and accuracy of the procedure was tested on two solid phantoms with superficial markings visible on both endoscopy and CT images. The first phantom was T-shaped tube with X-marks etched on the interior. The second phantom was an anatomically correct skull phantom with a phantom superficial lesion placed on the pharyngeal surface. Markings were contoured on the endoscope images and compared with contours delineated in the treatment planning system based on the CT images. Clinical feasibility was tested on three patients with early stage glottic cancer. Image-based rendering using manually identified landmarks was used to improve the registration. RESULTS: Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy was 1.5-3.5 mm, depending on the endoscope position relative to the markings. Intraobserver standard variation was 0.5 mm. Rotational accuracy was within 2°. Using the skull phantom, registration accuracy was assessed by calculating the average surface minimum distance between the endoscopy and treatment planning contours. The average surface distance was 0.92 mm with 93% of all points in the 2D-endoscopy ROI within 1.5 mm of any point within the ROI contoured in the treatment planning software. This accuracy is limited by the CT imaging resolution and the electromagnetic (EM) sensor accuracy. The clinical testing demonstrated that endoscopic contouring is feasible. With registration based on em tracking only, accuracy was 5.6-8.4 mm. Image-based registration reduced this error to less than 3.5 mm and enabled endoscopic contouring in all cases. CONCLUSIONS: Registration of contours generated on 2D endoscopic images to 3D planning space is feasible, with accuracy smaller than typical set-up margins. Used in addition to standard 3D contouring methods in radiation planning, the technology may improve gross tumour volume (GTV) delineation for superficial tumors in luminal sites that are only visible in endoscopy.

Effects of Mn levels on resistance of Bacillus megaterium spores to heat, radiation and hydrogen peroxide.

AIMS: To determine the effects of Mn levels in Bacillus megaterium sporulation and spores on spore resistance. METHODS AND RESULTS: Bacillus megaterium was sporulated with no added MnCl(2) and up to 1 mmol l(-1) MnCl(2). The resultant spores were purified and loosely bound Mn removed, and spore Mn levels were found to vary c. 100-fold. The Mn level had no effect on spore γ-radiation resistance, but B. megaterium spores with elevated Mn levels had higher resistance to UVC radiation (as did Bacillus subtilis spores), wet and dry heat and H(2)O(2). However, levels of dipicolinic acid and the DNA-protective α/ß-type small, acid-soluble spore proteins were the same in spores with high and low Mn levels. CONCLUSIONS: Mn levels either in sporulation or in spores are important factors in determining levels of B. megaterium spore resistance to many agents, with the exception of γ-radiation. SIGNIFICANCE AND IMPACT OF THE STUDY: The Mn level in sporulation is an important factor to consider when resistance properties of B. megaterium spores are examined, and will influence the UV resistance of B. subtilis spores, some of which are used as biological dosimeters.

Demons deformable registration for CBCT-guided procedures in the head and neck: convergence and accuracy.

PURPOSE: The accuracy and convergence behavior of a variant of the Demons deformable registration algorithm were investigated for use in cone-beam CT (CBCT)-guided procedures of the head and neck. Online use of deformable registration for guidance of therapeutic procedures such as image-guided surgery or radiation therapy places trade-offs on accuracy and computational expense. This work describes a convergence criterion for Demons registration developed to balance these demands; the accuracy of a multiscale Demons implementation using this convergence criterion is quantified in CBCT images of the head and neck. METHODS: Using an open-source "symmetric" Demons registration algorithm, a convergence criterion based on the change in the deformation field between iterations was developed to advance among multiple levels of a multiscale image pyramid in a manner that optimized accuracy and computation time. The convergence criterion was optimized in cadaver studies involving CBCT images acquired using a surgical C-arm prototype modified for 3D intraoperative imaging. CBCT-to-CBCT registration was performed and accuracy was quantified in terms of the normalized cross-correlation (NCC) and target registration error (TRE). The accuracy and robustness of the algorithm were then tested in clinical CBCT images of ten patients undergoing radiation therapy of the head and neck. RESULTS: The cadaver model allowed optimization of the convergence factor and initial measurements of registration accuracy: Demons registration exhibited TRE=(0.8+/-0.3) mm and NCC =0.99 in the cadaveric head compared to TRE=(2.6+/-1.0) mm and NCC=0.93 with rigid registration. Similarly for the patient data, Demons registration gave mean TRE=(1.6+/-0.9) mm compared to rigid registration TRE=(3.6+/-1.9) mm, suggesting registration accuracy at or near the voxel size of the patient images (1 x 1 x 2 mm3). The multiscale implementation based on optimal convergence criteria completed registration in 52 s for the cadaveric head and in an average time of 270 s for the larger FOV patient images. CONCLUSIONS: Appropriate selection of convergence and multiscale parameters in Demons registration was shown to reduce computational expense without sacrificing registration performance. For intraoperative CBCT imaging with deformable registration, the ability to perform accurate registration within the stringent time requirements of the operating environment could offer a useful clinical tool allowing integration of preoperative information while accurately reflecting changes in the patient anatomy. Similarly for CBCT-guided radiation therapy, fast accurate deformable registration could further augment high-precision treatment strategies.

Automatic image-to-world registration based on x-ray projections in cone-beam CT-guided interventions.

Intraoperative imaging offers a means to account for morphological changes occurring during the procedure and resolve geometric uncertainties via integration with a surgical navigation system. Such integration requires registration of the image and world reference frames, conventionally a time consuming, error-prone manual process. This work presents a method of automatic image-to-world registration of intraoperative cone-beam computed tomography (CBCT) and an optical tracking system. Multimodality (MM) markers consisting of an infrared (IR) reflective sphere with a 2 mm tungsten sphere (BB) placed precisely at the center were designed to permit automatic detection in both the image and tracking (world) reference frames. Image localization is performed by intensity thresholding and pattern matching directly in 2D projections acquired in each CBCT scan, with 3D image coordinates computed using backprojection and accounting for C-arm geometric calibration. The IR tracking system localized MM markers in the world reference frame, and the image-to-world registration was computed by rigid point matching of image and tracker point sets. The accuracy and reproducibility of the automatic registration technique were compared to conventional (manual) registration using a variety of marker configurations suitable to neurosurgery (markers fixed to cranium) and head and neck surgery (markers suspended on a subcranial frame). The automatic technique exhibited subvoxel marker localization accuracy (< 0.8 mm) for all marker configurations. The fiducial registration error of the automatic technique was (0.35 +/-0.01) mm, compared to (0.64 +/- 0.07 mm) for the manual technique, indicating improved accuracy and reproducibility. The target registration error (TRE) averaged over all configurations was 1.14 mm for the automatic technique, compared to 1.29 mm for the manual in accuracy, although the difference was not statistically significant (p = 0.3). A statistically significant improvement in precision was observed-specifically, the standard deviation in TRE was 0.2 mm for the automatic technique versus 0.34 mm for the manual technique (p = 0.001). The projection-based automatic registration technique demonstrates accuracy and reproducibility equivalent or superior to the conventional manual technique for both neurosurgical and head and neck marker configurations. Use of this method with C-arm CBCT eliminates the burden of manual registration on surgical workflow by providing automatic registration of surgical tracking in 3D images within approximately 20 s of acquisition, with registration automatically updated with each CBCT scan. The automatic registration method is undergoing integration in ongoing clinical trials of intraoperative CBCT-guided head and neck surgery.

Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.

OBJECTIVES: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. METHODS: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. RESULTS: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35 x 10(-10), rs13119723 p = 8.60 x 10(-8), rs6840978 p = 3.0 7x 10(-8), rs6822844 p = 2.77 x 10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86 x 10(-5)). CONCLUSIONS: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis.

Association mapping and candidate gene studies within inflammatory bowel diseases (IBD) linkage regions, as well as genome-wide association studies in Crohn's disease (CD) have led to the discovery of multiple risk genes, but these explain only a fraction of the genetic susceptibility observed in IBD. We have thus been pursuing a region on chromosome 3p21-22 showing linkage to CD and ulcerative colitis (UC) using a gene-centric association mapping approach. We identified 12 functional candidate genes by searching for literature cocitations with relevant keywords and for gene expression patterns consistent with immune/intestinal function. We then performed an association study composed of a screening phase, where tagging single nucleotide polymorphisms (SNPs) were evaluated in 1,020 IBD patients, and an independent replication phase in 745 IBD patients. These analyses identified and replicated significant association with IBD for four SNPs within a 1.2 Mb linkage disequilibrium region. We then identified a non-synonymous coding variant (rs3197999, R689C) in the macrophage-stimulating 1 (MST1) gene (P-value 3.62 x 10(-6)) that accounts for the association signal, and shows association with both CD and UC. MST1 encodes macrophage-stimulating protein (MSP), a protein regulating the innate immune responses to bacterial ligands. R689C is predicted to interfere with MSP binding to its receptor, suggesting a role for this gene in the pathogenesis of IBD.

MAST3: a novel IBD risk factor that modulates TLR4 signaling.

Inflammatory bowel disease (IBD) is a chronic disorder caused by multiple factors in a genetically susceptible host. Significant advances in the study of genetic susceptibility have highlighted the importance of the innate immune system in this disease. We previously completed a genome-wide linkage study and found a significant locus (IBD6) on chromosome 19p. We were interested in identifying the causal variant in IBD6. We performed a two-stage association mapping study. In stage 1, 1530 single-nucleotide polymorphisms (SNPs) were selected from the HapMap database and genotyped in 761 patients with IBD. Among the SNPs that passed the threshold for replication, 26 were successfully genotyped in 754 additional patients (stage 2). One intronic variant, rs273506, located in the microtubule-associated serine/threonine-protein kinase gene-3 (MAST3), was found to be associated in both stages (pooled P=1.8 x 10(-4)). We identified four MAST3 coding variants, including a non-synonymous SNP rs8108738, correlated to rs273506 and associated with IBD. To test whether MAST3 was expressed in cells of interest, we performed expression assays, which showed abundant expression of MAST3 in antigen-presenting cells and in lymphocytes. The knockdown of MAST3 specifically decreased Toll-like receptor-4-dependent NF-kappaB activity. Our findings are additional proofs of the pivotal role played by modulators of NF-kappaB activity in IBD pathogenesis.

Geometric calibration of a mobile C-arm for intraoperative cone-beam CT.

A geometric calibration method that determines a complete description of source-detector geometry was adapted to a mobile C-arm for cone-beam computed tomography (CBCT). The non-iterative calibration algorithm calculates a unique solution for the positions of the source (X(s), Y(s), Z(s)), detector (X(d), Y(d), Z(d)), piercing point (U(o), V(o)), and detector rotation angles (phi, theta, eta) based on projections of a phantom consisting of two plane-parallel circles of ball bearings encased in a cylindrical acrylic tube. The prototype C-arm system was based on a Siemens PowerMobil modified to provide flat-panel CBCT for image-guided interventions. The magnitude of geometric nonidealities in the source-detector orbit was measured, and the short-term (approximately 4 h) and long-term (approximately 6 months) reproducibility of the calibration was evaluated. The C-arm exhibits large geometric nonidealities due to mechanical flex, with maximum departures from the average semicircular orbit of deltaU(o) = 15.8 mm and deltaV(o) = 9.8 mm (for the piercing point), deltaX and deltaY = 6-8 mm and deltaZ = 1 mm (for the source and detector), and deltaphi approximately 2.9 degrees, deltatheta approximately 1.9 degrees, and delta eta approximately 0.8 degrees (for the detector tilt/rotation). Despite such significant departures from a semicircular orbit, these system parameters were found to be reproducible, and therefore correctable by geometric calibration. Short-term reproducibility was < 0.16 mm (subpixel) for the piercing point coordinates, < 0.25 mm for the source-detector X and Y, < 0.035 mm for the source-detector Z, and < 0.02 degrees for the detector angles. Long-term reproducibility was similarly high, demonstrated by image quality and spatial resolution measurements over a period of 6 months. For example, the full-width at half-maximum (FWHM) in axial images of a thin steel wire increased slightly as a function of the time (delta) between calibration and image acquisition: FWHM=0.62, 0.63, 0.66, 0.71, and 0.72 mm at delta = 0 s, 1 h, 1 day, 1 month, and 6 months, respectively. For ongoing clinical trials in CBCT-guided surgery at our institution, geometric calibration is conducted monthly to provide sufficient three-dimensional (3D) image quality while managing time and workflow considerations of the calibration and quality assurance process. The sensitivity of 3D image quality to each of the system parameters was investigated, as was the tolerance to systematic and random errors in the geometric parameters, showing the most sensitive parameters to be the piercing point coordinates (U(o), V(o)) and in-plane positions of the source (X(s), Y(s)) and detector (X(d), Y(d)). Errors in the out-of-plane position of the source (Z(s)) and detector (Z(d)) and the detector angles (phi, theta, eta) were shown to have subtler effects on 3D image quality.

Whole-genome association study of bipolar disorder.

We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

Soft-tissue detectability in cone-beam CT: evaluation by 2AFC tests in relation to physical performance metrics.

Soft-tissue detectability in cone-beam computed tomography (CBCT) was evaluated via two-alternative forced-choice (2AFC) tests. Investigations included the dependence of detectability on radiation dose, the influence of the asymmetric three-dimensional (3D) noise-power spectrum (NPS) in axial and sagittal or coronal planes, and the effect of prior knowledge on detectability. Custom-built phantoms (approximately 15 cm diameter cylinders) containing soft-tissue-simulating spheres of variable contrast and diameter were imaged on an experimental CBCT bench. The proportion of correct responses (Pcorr) in 2AFC tests was analyzed as a figure of merit, ideally equal to the area under the receiver operating characteristic curve. Pcorr was evaluated as a function of the sphere diameter (1.6-12.7 mm), contrast (20-165 HU), dose (1-7 mGy), plane of visualization (axial/sagittal), apodization filter (Hanning and Ram-Lak), and prior knowledge provided to the observer [ranging from stimulus known exactly (SKE) to stimulus unknown (SUK)]. Detectability limits were characterized in terms of the dose required to achieve a given level of Pcorr (e.g., 70%). For example, a 20 HU stimulus of diameter down to approximately 6 mm was detected with Pcorr 70% at dose > or =2 mGy. Detectability tended to be greater in axial than in sagittal planes, an effect amplified by sharper apodization filters in a manner consistent with 3D NPS asymmetry. Prior knowledge had a marked influence on detectability--e.g., Pcorr for a approximately 6 mm (20 HU) sphere was approximately 55%-65% under SUK conditions, compared to approximately 70%-85% for SKE conditions. Human observer tests suggest practical implications for implementation of CBCT: (i) Detectability limits help to define minimum-dose imaging techniques for specific imaging tasks; (ii) detectability of a given structure can vary between axial and sagittal/coronal planes, owing to the spatial-frequency content of the 3D NPS in relation to the imaging task; and (iii) performance under SKE conditions (e.g., image guidance tasks in which lesion characteristics are known) is maintained at a lower dose than in SUK conditions (e.g., diagnostic tasks in which lesion characteristics are unknown).

Intraoperative cone-beam CT for image-guided tibial plateau fracture reduction.

OBJECTIVES: A mobile isocentric C-arm was modified in our laboratory in collaboration with Siemens Medical Solutions to include a large-area flat-panel detector providing multi-mode fluoroscopy and cone-beam CT (CBCT) imaging. This technology is an important advance over existing intraoperative imaging (e.g., Iso-C(3D)), offering superior image quality, increased field of view, higher spatial resolution, and soft-tissue visibility. The aim of this study was to assess the system's performance and image quality in tibial plateau (TP) fracture reconstruction. METHODS: Three TP fractures were simulated in fresh-frozen cadaveric knees through combined axial loading and lateral impact. The fractures were reduced through a lateral approach and assessed by fluoroscopy. The reconstruction was then assessed using CBCT. If necessary, further reduction and localization of remaining displaced bone fragments was performed using CBCT images for guidance. CBCT image quality was assessed with respect to projection speed, dose and filtering technique. RESULTS: CBCT imaging provided exquisite visualization of articular details, subtle fragment detection and localization, and confirmation of reduction and implant placement. After fluoroscopic images indicated successful initial reduction, CBCT imaging revealed areas of malalignment and displaced fragments. CBCT facilitated fragment localization and improved anatomic reduction. CBCT image noise increased gradually with reduced dose, but little difference in images resulted from increased projections. High-resolution reconstruction provided better delineation of plateau depressions. CONCLUSION: This study demonstrated a clear advantage of intraoperative CBCT over 2D fluoroscopy and Iso-C(3D) in TP fracture fixation. CBCT imaging provided benefits in fracture type diagnosis, localization of fracture fragments, and intraoperative 3D confirmation of anatomic reduction.

Image quality and localization accuracy in C-arm tomosynthesis-guided head and neck surgery.

The image quality and localization accuracy for C-arm tomosynthesis and cone-beam computed tomography (CBCT) guidance of head and neck surgery were investigated. A continuum in image acquisition was explored, ranging from a single exposure (radiograph) to multiple projections acquired over a limited arc (tomosynthesis) to a full semicircular trajectory (CBCT). Experiments were performed using a prototype mobile C-arm modified to perform 3D image acquisition (a modified Siemens PowerMobil). The tradeoffs in image quality associated with the extent of the source-detector arc (theta(tot)), the number of projection views, and the total imaging dose were evaluated in phantom and cadaver studies. Surgical localization performance was evaluated using three cadaver heads imaged as a function of theta(tot). Six localization tasks were considered, ranging from high-contrast feature identification (e.g., tip of a K-wire pointer) to more challenging soft-tissue delineation (e.g., junction of the hard and soft palate). Five head and neck surgeons and one radiologist participated as observers. For each localization task, the 3D coordinates of landmarks pinpointed by each observer were analyzed as a function of theta(tot). For all tomosynthesis angles, image quality was highest in the coronal plane, whereas sagittal and axial planes exhibited a substantial decrease in spatial resolution associated with out-of-plane blur and distortion. Tasks involving complex, lower-contrast features demonstrated steeper degradation with smaller tomosynthetic arc. Localization accuracy in the coronal plane was correspondingly high, maintained to < 3 mm down to theta(tot) approximately 30 degrees, whereas sagittal and axial localization degraded rapidly below theta(tot) approximately 60 degrees. Similarly, localization precision was better than approximately 1 mm within the coronal plane, compared to approximately 2-3 mm out-of-plane for tomosynthesis angles below theta(tot) approximately 45 degrees. An overall 3D localization accuracy of approximately 2.5 mm was achieved with theta(tot) approximately 90 degrees for most tasks. The high in-plane spatial resolution, short scanning time, and low radiation dose characteristic of tomosynthesis may enable the surgeon to collect near real-time images throughout the procedure with minimal interference to surgical workflow. Therefore, tomosynthesis could provide a useful addition to the image-guided surgery arsenal, providing on-demand, high quality image updates, complemented by CBCT at critical milestones in the surgical procedure.

Intraoperative cone-beam CT for guidance of head and neck surgery: Assessment of dose and image quality using a C-arm prototype.

Cone-beam computed tomography (CBCT) with a flat-panel detector represents a promising modality for intraoperative imaging in interventional procedures, demonstrating sub-mm three-dimensional (3D) spatial resolution and soft-tissue visibility. Measurements of patient dose and in-room exposure for CBCT-guided head and neck surgery are reported, and the 3D imaging performance as a function of dose and other acquisition/reconstruction parameters is investigated. Measurements were performed on a mobile isocentric C-arm (Siemens PowerMobil) modified in collaboration with Siemens Medical Solutions (Erlangen, Germany) to provide flat-panel CBCT. Imaging dose was measured in a custom-built 16 cm cylindrical head phantom at four positions (isocenter, anterior, posterior, and lateral) as a function of kVp (80-120 kVp) and C-arm trajectory ("tube-under" and "tube-over" half-rotation orbits). At 100 kVp, for example ("tube-under" orbit), the imaging dose was 0.059 (isocenter), 0.022 (anterior), 0.10 (posterior), and 0.056 (lateral) mGy/ mAs, with scans at approximately 50 and approximately 170 mAs typical for visualization of bony and soft-tissue structures, respectively. Dose to radiosensitive structures (viz., the eyes and thyroid) were considered in particular: significant dose sparing to the eyes (a factor of 5) was achieved using a "tube-under" (rather than "tube-over") half-rotation orbit; a thyroid shield (0.5 mm Pb-equivalent) gave moderate reduction in thyroid dose due to x-ray scatter outside the primary field of view. In-room exposure was measured at positions around the operating table and up to 2 m from isocenter. A typical CBCT scan (10 mGy to isocenter) gave in-air exposure ranging from 29 mR (0.26 mSv) at 35 cm from isocenter, to <0.5 mR (<0.005 mSv) at 2 m from isocenter. Three-dimensional (3D) image quality was assessed in CBCT reconstructions of an anthropomorphic head phantom containing contrast-detail spheres (11-103 HU; 1.6-12.7 mm) and a natural human skeleton. The contrast-to-noise ratio (CNR) was evaluated across a broad range of dose (0.6-23.3 mGy). CNR increased as the square root of dose, with excellent visualization of bony and soft-tissue structures achieved at approximately 3 mGy (0.10 mSv) and approximately 10 mGy (0.35 mSv), respectively. The prototype C-arm demonstrates CBCT image quality sufficient for guidance of head and neck procedures based on soft-tissue and bony anatomy at dose levels low enough for repeat intraoperative imaging, with total dose over the course of the procedure comparable to or less than the effective dose of a typical (2 mSv) diagnostic CT of the head.

A simple, direct method for x-ray scatter estimation and correction in digital radiography and cone-beam CT.

X-ray scatter poses a significant limitation to image quality in cone-beam CT (CBCT), resulting in contrast reduction, image artifacts, and lack of CT number accuracy. We report the performance of a simple scatter correction method in which scatter fluence is estimated directly in each projection from pixel values near the edge of the detector behind the collimator leaves. The algorithm operates on the simple assumption that signal in the collimator shadow is attributable to x-ray scatter, and the 2D scatter fluence is estimated by interpolating between pixel values measured along the top and bottom edges of the detector behind the collimator leaves. The resulting scatter fluence estimate is subtracted from each projection to yield an estimate of the primary-only images for CBCT reconstruction. Performance was investigated in phantom experiments on an experimental CBCT bench-top, and the effect on image quality was demonstrated in patient images (head, abdomen, and pelvis sites) obtained on a preclinical system for CBCT-guided radiation therapy. The algorithm provides significant reduction in scatter artifacts without compromise in contrast-to-noise ratio (CNR). For example, in a head phantom, cupping artifact was essentially eliminated, CT number accuracy was restored to within 3%, and CNR (breast-to-water) was improved by up to 50%. Similarly in a body phantom, cupping artifact was reduced by at least a factor of 2 without loss in CNR. Patient images demonstrate significantly increased uniformity, accuracy, and contrast, with an overall improvement in image quality in all sites investigated. Qualitative evaluation illustrates that soft-tissue structures that are otherwise undetectable are clearly delineated in scatter-corrected reconstructions. Since scatter is estimated directly in each projection, the algorithm is robust with respect to system geometry, patient size and heterogeneity, patient motion, etc. Operating without prior information, analytical modeling, or Monte Carlo, the technique is easily incorporated as a preprocessing step in CBCT reconstruction to provide significant scatter reduction.

Investigation of C-arm cone-beam CT-guided surgery of the frontal recess.

OBJECTIVE/HYPOTHESIS: A cone-beam CT (CBCT) imaging system based on a mobile C-arm (Siemens PowerMobil) incorporating a high-performance flat-panel detector (Varian PaxScan) has been developed in our laboratory. We hypothesize that intraoperative C-arm CBCT provides image quality and guidance performance sufficient to assist surgical approach to the frontal recess. STUDY DESIGN: A preclinical prospective study was conducted using six cadaver heads to assess the performance characteristics and the potential clinical utility of this imaging system. METHODS: The mobile C-arm was employed for intraoperative CBCT guidance of the endoscopic approach to twelve frontal recesses. RESULTS: The imaging system is capable of sub-mm 3D spatial resolution with bone and soft-tissue visibility and a field of view sufficient for guidance of head and neck surgery. The system can generate intraoperative, volumetric CT images rapidly with an acceptably low radiation exposure to the patient and with image quality sufficient for most surgical tasks. Moreover, the system is portable and compatible with the surgical setup, providing excellent access to the patient. Finally, the accuracy of the system is not bound to a registration process. CONCLUSIONS: The ability to create updated images as surgery progresses introduces the concept of 'near-real-time' CT guidance for head and neck surgery. We found that the use of CBCT increased surgical confidence in accessing the frontal recess, resolved ambiguities with anatomical variations, and provided valuable teaching information to surgeons in training in both preoperative planning and correlation between tri-planar CT scans and intraoperative endoscopic findings.

Accumulation of Mn(II) in Deinococcus radiodurans facilitates gamma-radiation resistance.

Deinococcus radiodurans is extremely resistant to ionizing radiation. How this bacterium can grow under chronic gamma radiation [50 grays (Gy) per hour] or recover from acute doses greater than 10 kGy is unknown. We show that D. radiodurans accumulates very high intracellular manganese and low iron levels compared with radiation-sensitive bacteria and that resistance exhibits a concentration-dependent response to manganous chloride [Mn(II)]. Among the most radiation-resistant bacterial groups reported, Deinococcus, Enterococcus, Lactobacillus, and cyanobacteria accumulate Mn(II). In contrast, Shewanella oneidensis and Pseudomonas putida have high iron but low intracellular manganese concentrations and are very sensitive. We propose that Mn(II) accumulation facilitates recovery from radiation injury.