Registration Success Rate Research Articles

Development of an automated dual‐mode supercritical fluid chromatography and reversed‐phase liquid chromatography mass‐directed purification system for small‐molecule drug discovery

We report the development of a dual-mode mass-directed supercritical fluid chromatography and reversed-phase liquid chromatography purification system. The addition of a third pump allows for flexible mobile phase control between the two techniques, and enables operation of either chromatography mode within minutes by activation of a set of switching valves on a single system. Software control, fluidic pathways, interface to the mass spectrometer, and fraction collection have been modified for compatibility between both separation methods. The conditioning solvent and tuning parameters for the mass spectrometer were adjusted to achieve an ideal signal trace in either mode with good linearity (r(2) > 0.970) over a range of concentrations and minimal noise for accurate peak detection and isolation. The registration success rate is 90% and overall sample recovery for either technique is 80-90%. Combining two orthogonal separation and purification modes in one single system has improved the purification throughput of complex mixtures and has been a valuable, cost-saving tool in our laboratory.

SU‐E‐J‐67: Regularized Deformable Registration of Computed Tomography Images Using Multiple Voxel Resolutions for Four Dimensional Radiation Therapy

Purpose: Accurate, speedy, and robust image registration is deemed crucial in radiation therapy of cancer management. A multi‐resolution deformable image registration (DIR) using regularization strategy was developed for four dimensional radiation therapy. Methods: A multi‐resolution based deformable registration model was implemented with the regularization of energy term to smooth the deformation field. A B‐Spline model, although other models such as demons are applicable as well, was employed as the transformation with the Mattes mutual information as the objective function that was to be optimized the limited memory Broyden‐Fletcher‐Goldfarb‐Shanno algorithm (L‐BFGS) optimizer. A three level voxel resolution model was utilized for the coarse‐to‐fine strategy to improve the registration success rate and remove local optima at coarser scales. A regularization term was applied to the objective function and its parameters were investigated to have the optimal effect on the deformation vector field. Four dimensional computed tomography (4DCT) images from four thoracic and four abdominal cancer patients were used to evaluate the algorithm. Results: A quarter, half and full of the original voxel resolutions were adopted in the three levels respectively from the coarsest to the finest. An accuracy of 2 mm was achievable for thoracic cancer patients while slightly larger residual error at the average of 3 mm was observed in abdominal cancer patients. Under the same condition, larger errors were found from the calculation with a single resolution model. The smoothness of vector field was significantly improved with the regularization term. The parameters, however, have to be determined empirically. This feature is particularly useful when conducting dose warping. Conclusion: Significant improvement in DIR accuracy and robustness with the proposed algorithm is achieved. The novel deformable registration model, with more systematic study, will find its widespread application in radiation therapy.

Robust 2D/3D registration for fast-flexion motion of the knee joint using hybrid optimization

Previously, we proposed a 2D/3D registration method that uses Powell's algorithm to obtain 3D motion of a knee joint by 3D computed-tomography and bi-plane fluoroscopic images. The 2D/3D registration is performed consecutively and automatically for each frame of the fluoroscopic images. This method starts from the optimum parameters of the previous frame for each frame except for the first one, and it searches for the next set of optimum parameters using Powell's algorithm. However, if the flexion motion of the knee joint is fast, it is likely that Powell's algorithm will provide a mismatch because the initial parameters are far from the correct ones. In this study, we applied a hybrid optimization algorithm (HPS) combining Powell's algorithm with the Nelder-Mead simplex (NM-simplex) algorithm to overcome this problem. The performance of the HPS was compared with the separate performances of Powell's algorithm and the NM-simplex algorithm, the Quasi-Newton algorithm and hybrid optimization algorithm with the Quasi-Newton and NM-simplex algorithms with five patient data sets in terms of the root-mean-square error (RMSE), target registration error (TRE), success rate, and processing time. The RMSE, TRE, and the success rate of the HPS were better than those of the other optimization algorithms, and the processing time was similar to that of Powell's algorithm alone.

Residual Seminal Vesicle Displacement in Marker-Based Image-Guided Radiotherapy for Prostate Cancer and the Impact on Margin Design

The objectives of this study were to quantify residual interfraction displacement of seminal vesicles (SV) and investigate the efficacy of rotation correction on SV displacement in marker-based prostate image-guided radiotherapy (IGRT). We also determined the effect of marker registration on the measured SV displacement and its impact on margin design. SV displacement was determined relative to marker registration by using 296 cone beam computed tomography scans of 13 prostate cancer patients with implanted markers. SV were individually registered in the transverse plane, based on gray-value information. The target registration error (TRE) for the SV due to marker registration inaccuracies was estimated. Correlations between prostate gland rotations and SV displacement and between individual SV displacements were determined. The SV registration success rate was 99%. Displacement amounts of both SVs were comparable. Systematic and random residual SV displacements were 1.6 mm and 2.0 mm in the left-right direction, respectively, and 2.8 mm and 3.1 mm in the anteroposterior (AP) direction, respectively. Rotation correction did not reduce residual SV displacement. Prostate gland rotation around the left-right axis correlated with SV AP displacement (R(2) = 42%); a correlation existed between both SVs for AP displacement (R(2) = 62%); considerable correlation existed between random errors of SV displacement and TRE (R(2) = 34%). Considerable residual SV displacement exists in marker-based IGRT. Rotation correction barely reduced SV displacement, rather, a larger SV displacement was shown relative to the prostate gland that was not captured by the marker position. Marker registration error partly explains SV displacement when correcting for rotations. Correcting for rotations, therefore, is not advisable when SV are part of the target volume. Margin design for SVs should take these uncertainties into account.

Biomechanically constrained groupwise ultrasound to CT registration of the lumbar spine

We present a groupwise US to CT registration algorithm for guiding percutaneous spinal interventions. In addition, we introduce a comprehensive validation scheme that accounts for changes in the curvature of the spine between preoperative and intraoperative imaging. In our registration methodology, each vertebra in CT is treated as a sub-volume and transformed individually. A biomechanical model is used to constrain the displacement of the vertebrae relative to one another. The sub-volumes are then reconstructed into a single volume. During each iteration of registration, an US image is simulated from the reconstructed CT volume and an intensity-based similarity metric is calculated with the real US image. Validation studies are performed on CT and US images from a sheep cadaver, five patient-based phantoms designed to preserve realistic curvatures of the spine and a sixth patient-based phantom where the curvature of the spine is changed between preoperative and intraoperative imaging. For datasets where the spine curve between two imaging modalities was artificially perturbed, the proposed methodology was able to register initial misalignments of up to 20mm with a success rate of 95%. For the phantom with a physical change in the curvature of the spine introduced between the US and CT datasets, the registration success rate was 98.5%. Finally, the registration success rate for the sheep cadaver with soft-tissue information was 87%. The results demonstrate that our algorithm allows for robust registration of US and CT datasets, regardless of a change in the patients pose between preoperative and intraoperative image acquisitions.

TU‐FF‐A3‐05: Optimizing KV Fluoro Acquisition for Prostate Intrafraction Motion Evaluation

Purpose: Commercially available gantry mounted kV imagers are currently restricted to manual fluoroscopy acquisitions with fixed mAs & frame rate, limiting use of fluoroscopy for prostate intrafraction motion measurement. For consideration in future acquisition improvements, we investigate the parameters required to optimize the 3D accuracy of prostate intrafraction localization while minimizing imaging dose. Method and Materials: Prostate intrafraction motion is measured at our clinic using simultaneous kV fluoroscopy to visualize implanted markers for a hypofractionated radiotherapy protocol. For a 5‐beam step‐and‐shoot IMRT delivery we compare the current technique with acquiring images between MLC segments. Effects of imaging frequency and of including acquisitions during gantry rotation were also considered. The 3D localization accuracy was evaluated using simulations with existing sagittal cine‐MRI images from 6 patients consisting of 490 motion tracks for ∼8 minutes/track. Dose was evaluated using surface and central axis measurements on a 30‐cm diameter acrylic phantom, assuming adequate mAs values to achieve 80% registration success rate. Results: Simulations with the cine‐MRI data showed that 3D accuracy is acceptable even for low imaging frequencies: 95% of measurements were within 1.0 mm when imaging every 30s, and within 1.2 mm for 60s. 3D accuracy is adequate when imaging between MLC segments only (95% within 1.0 mm, 98% within 1.6 mm), with minor improvement when acquiring also during gantry rotation (95% within 1.0 mm, 98% within 1.5 mm). Maximum dose was lowered to 1.4 mGy when imaging only between MLC segments with gantry dependant mAs, compared to 3.3 mGy for the current technique and 21.1 mGy for a CBCT. Conclusion: Optimal intrafraction fluoroscopy measurement is achieved with adjustable acquisition frame rate, synchronization with MV beam delivery (acquisition between segments), and programmable gantry dependent mAs, resulting in high 3D accuracy and low imaging dose. Conflict of Interest: Partially supported by NIH Grant CA118037.

The detection and significance of subtle changes in mixed-signal brain lesions by serial MRI scan matching and spatial normalization

The purpose of this work is to detect and assess the significance of subtle signal changes in mixed-signal lesions based on serial MRI scan matching. Pairs of serially acquired T1-weighted volume MR images from 20 normal controls and seven patients with epilepsy were matched and difference images obtained. The precision and consistency of the registration were evaluated. The Gaussian noise level in the difference images was determined automatically. A structured difference filter was then used to segment structured (changed) voxels from the Gaussian noise. In the controls, the structured difference images were normalized into Talairach space, resulting in a structured noise map. The significance of changes in patients was assessed by spatial normalization and comparison with the structured noise map. The precision and consistency of the co-registration were ≤0.06 mm with a registration success rate of 100%. The Gaussian noise level in the difference images was in the range 3.0–6.9. In the controls, an average of 1.6% of the brain voxels were classified as structured. Since-based registration resulted in a reduction of < 1 % in the amount of structure compared to linear interpolation. The structured noise map in controls showed high noise density in areas affected by image artefacts. We show examples of significant changes found in lesions which had been reported as unchanged on visual inspection. A novel quantitative approach has been presented for the detection and quantification of subtle signal changes in lesions. This method is of potential clinical value in the non-invasive characterization of signal change and biological behaviour of neoplastic lesions.