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1.  A quantitative comparison of the performance of three deformable registration algorithms in radiotherapy 
We present an evaluation of various non-rigid registration algorithms for the purpose of compensating interfractional motion of the target volume and organs at risk areas when acquiring CBCT image data prior to irradiation. Three different deformable registration (DR) methods were used: the Demons algorithm implemented in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom-developed piecewise methods using either a Normalized Correlation or a Mutual Information metric (featureletNC and featureletMI). These methods were tested on data acquired using a novel purpose-built phantom for deformable registration and clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity coefficient (DSC) between manually drawn contours and the contours generated by a derived deformation field of the structures in question was compared to the result obtained with rigid registration (RR). For the phantom, the piecewise methods were slightly superior, the featureletNC for the intramodality and the featureletMI for the intermodality registrations. For the prostate cases in less than 50% of the images studied the DSC was improved over RR. Deformable registration methods improved the outcome over a rigid registration for lung cases and in the phantom study, but not in a significant way for the prostate study. A significantly superior deformation method could not be identified.
doi:10.1016/j.zemedi.2013.07.006
PMCID: PMC3865361  PMID: 23969092
Deformable registration; radiotherapy; organ motion; Deformierbare Registrierung; Radiotherapie; Organbewegung
2.  High-performance GPU-based rendering for real-time, rigid 2D/3D-image registration and motion prediction in radiation oncology 
A common problem in image-guided radiation therapy (IGRT) of lung cancer as well as other malignant diseases is the compensation of periodic and aperiodic motion during dose delivery. Modern systems for image-guided radiation oncology allow for the acquisition of cone-beam computed tomography data in the treatment room as well as the acquisition of planar radiographs during the treatment. A mid-term research goal is the compensation of tumor target volume motion by 2D/3D registration. In 2D/3D registration, spatial information on organ location is derived by an iterative comparison of perspective volume renderings, so-called digitally rendered radiographs (DRR) from computed tomography volume data, and planar reference x-rays. Currently, this rendering process is very time consuming, and real-time registration, which should at least provide data on organ position in less than a second, has not come into existence. We present two GPU-based rendering algorithms which generate a DRR of 512 × 512 pixels size from a CT dataset of 53 MB size at a pace of almost 100 Hz. This rendering rate is feasible by applying a number of algorithmic simplifications which range from alternative volume-driven rendering approaches – namely so-called wobbled splatting – to sub-sampling of the DRR-image by means of specialized raycasting techniques. Furthermore, general purpose graphics processing unit (GPGPU) programming paradigms were consequently utilized. Rendering quality and performance as well as the influence on the quality and performance of the overall registration process were measured and analyzed in detail. The results show that both methods are competitive and pave the way for fast motion compensation by rigid and possibly even non-rigid 2D/3D registration and, beyond that, adaptive filtering of motion models in IGRT.
doi:10.1016/j.zemedi.2011.06.002
PMCID: PMC3378472  PMID: 21782399
2D/3D-Registration; DRR; real-time; sparse sampling
3.  Monitoring tumor motion by real time 2D/3D registration during radiotherapy 
Background and purpose
In this paper, we investigate the possibility to use X-ray based real time 2D/3D registration for non-invasive tumor motion monitoring during radiotherapy.
Materials and methods
The 2D/3D registration scheme is implemented using general purpose computation on graphics hardware (GPGPU) programming techniques and several algorithmic refinements in the registration process. Validation is conducted off-line using a phantom and five clinical patient data sets. The registration is performed on a region of interest (ROI) centered around the planned target volume (PTV).
Results
The phantom motion is measured with an rms error of 2.56 mm. For the patient data sets, a sinusoidal movement that clearly correlates to the breathing cycle is shown. Videos show a good match between X-ray and digitally reconstructed radiographs (DRR) displacement. Mean registration time is 0.5 s.
Conclusions
We have demonstrated that real-time organ motion monitoring using image based markerless registration is feasible.
doi:10.1016/j.radonc.2011.07.031
PMCID: PMC3276833  PMID: 21885144
2D/3D registration; Radiotherapy; Organ motion
4.  Monitoring tumor motion by real time 2D/3D registration during radiotherapy 
Radiotherapy and Oncology  2012;102-142(2):274-280.
Background and purpose
In this paper, we investigate the possibility to use X-ray based real time 2D/3D registration for non-invasive tumor motion monitoring during radiotherapy.
Materials and methods
The 2D/3D registration scheme is implemented using general purpose computation on graphics hardware (GPGPU) programming techniques and several algorithmic refinements in the registration process. Validation is conducted off-line using a phantom and five clinical patient data sets. The registration is performed on a region of interest (ROI) centered around the planned target volume (PTV).
Results
The phantom motion is measured with an rms error of 2.56 mm. For the patient data sets, a sinusoidal movement that clearly correlates to the breathing cycle is shown. Videos show a good match between X-ray and digitally reconstructed radiographs (DRR) displacement. Mean registration time is 0.5 s.
Conclusions
We have demonstrated that real-time organ motion monitoring using image based markerless registration is feasible.
doi:10.1016/j.radonc.2011.07.031
PMCID: PMC3276833  PMID: 21885144
2D/3D registration; Radiotherapy; Organ motion
5.  Validation for 2D/3D registration II: The comparison of intensity- and gradient-based merit functions using a new gold standard data set 
Medical physics  2011;38(3):1491-1502.
Purpose:
A new gold standard data set for validation of 2D/3D registration based on a porcine cadaver head with attached fiducial markers was presented in the first part of this article. The advantage of this new phantom is the large amount of soft tissue, which simulates realistic conditions for registration. This article tests the performance of intensity- and gradient-based algorithms for 2D/3D registration using the new phantom data set.
Methods:
Intensity-based methods with four merit functions, namely, cross correlation, rank correlation, correlation ratio, and mutual information (MI), and two gradient-based algorithms, the backprojection gradient-based (BGB) registration method and the reconstruction gradient-based (RGB) registration method, were compared. Four volumes consisting of CBCT with two fields of view, 64 slice multidetector CT, and magnetic resonance-T1 weighted images were registered to a pair of kV x-ray images and a pair of MV images. A standardized evaluation methodology was employed. Targets were evenly spread over the volumes and 250 starting positions of the 3D volumes with initial displacements of up to 25 mm from the gold standard position were calculated. After the registration, the displacement from the gold standard was retrieved and the root mean square (RMS), mean, and standard deviation mean target registration errors (mTREs) over 250 registrations were derived. Additionally, the following merit properties were computed: Accuracy, capture range, number of minima, risk of nonconvergence, and distinctiveness of optimum for better comparison of the robustness of each merit.
Results:
Among the merit functions used for the intensity-based method, MI reached the best accuracy with an RMS mTRE down to 1.30 mm. Furthermore, it was the only merit function that could accurately register the CT to the kV x rays with the presence of tissue deformation. As for the gradient-based methods, BGB and RGB methods achieved subvoxel accuracy (RMS mTRE down to 0.56 and 0.70 mm, respectively). Overall, gradient-based similarity measures were found to be substantially more accurate than intensity-based methods and could cope with soft tissue deformation and enabled also accurate registrations of the MR-T1 volume to the kV x-ray image.
Conclusions:
In this article, the authors demonstrate the usefulness of a new phantom image data set for the evaluation of 2D/3D registration methods, which featured soft tissue deformation. The author’s evaluation shows that gradient-based methods are more accurate than intensity-based methods, especially when soft tissue deformation is present. However, the current nonoptimized implementations make them prohibitively slow for practical applications. On the other hand, the speed of the intensity-based method renders these more suitable for clinical use, while the accuracy is still competitive.
PMCID: PMC3089767  PMID: 21520861
2D/3D registration; image-guided therapy; gradient; intensity; rendering; ray-casting
6.  A comparative study on manual and automatic slice-to-volume registration of CT images 
European radiology  2009;19(11):2647-2653.
In order to assess the clinical relevance of a slice-to-volume registration algorithm, this technique was compared to manual registration. Reformatted images obtained from a diagnostic CT examination of the lower abdomen were reviewed and manually registered by 41 individuals. The results were refined by the algorithm. Furthermore, a fully automatic registration of the single slices to the whole CT examination, without manual initialization, was also performed. The manual registration error for rotation and translation was found to be 2.7±2.8 ° and 4.0±2.5 mm. The automated registration algorithm significantly reduced the registration error to 1.6±2.6 ° and 1.3±1.6 mm (p=0.01). In 3 of 41 (7.3%) registration cases, the automated registration algorithm failed completely. On average, the time required for manual registration was 213±197 s; automatic registration took 82±15 s. Registration was also performed without any human interaction. The resulting registration error of the algorithm without manual pre-registration was found to be 2.9±2.9 ° and 1.1±0.2 mm. Here, a registration took 91±6 s, on average. Overall, the automated registration algorithm improved the accuracy of manual registration by 59% in rotation and 325% in translation. The absolute values are well within a clinically relevant range.
doi:10.1007/s00330-009-1452-0
PMCID: PMC2855949  PMID: 19504108
Slice-to-volume registration algorithm; Manual registration; Fluoro CT; Computed tomography
7.  Stochastic rank correlation: A robust merit function for 2D/3D registration of image data obtained at different energies 
Medical physics  2009;36(8):3420-3428.
In this article, the authors evaluate a merit function for 2D/3D registration called stochastic rank correlation (SRC). SRC is characterized by the fact that differences in image intensity do not influence the registration result; it therefore combines the numerical advantages of cross correlation (CC)-type merit functions with the flexibility of mutual-information-type merit functions. The basic idea is that registration is achieved on a random subset of the image, which allows for an efficient computation of Spearman’s rank correlation coefficient. This measure is, by nature, invariant to monotonic intensity transforms in the images under comparison, which renders it an ideal solution for intramodal images acquired at different energy levels as encountered in intrafractional kV imaging in image-guided radiotherapy. Initial evaluation was undertaken using a 2D/3D registration reference image dataset of a cadaver spine. Even with no radiometric calibration, SRC shows a significant improvement in robustness and stability compared to CC. Pattern intensity, another merit function that was evaluated for comparison, gave rather poor results due to its limited convergence range. The time required for SRC with 5% image content compares well to the other merit functions; increasing the image content does not significantly influence the algorithm accuracy. The authors conclude that SRC is a promising measure for 2D/3D registration in IGRT and image-guided therapy in general.
PMCID: PMC2855948  PMID: 19746775
8.  Multiple window spatial registration error of a gamma camera: 133Ba point source as a replacement of the NEMA procedure 
Background
The accuracy of multiple window spatial resolution characterises the performance of a gamma camera for dual isotope imaging. In the present study we investigate an alternative method to the standard NEMA procedure for measuring this performance parameter.
Methods
A long-lived 133Ba point source with gamma energies close to 67Ga and a single bore lead collimator were used to measure the multiple window spatial registration error. Calculation of the positions of the point source in the images used the NEMA algorithm. The results were validated against the values obtained by the standard NEMA procedure which uses a liquid 67Ga source with collimation.
Results
Of the source-collimator configurations under investigation an optimum collimator geometry, consisting of a 5 mm thick lead disk with a diameter of 46 mm and a 5 mm central bore, was selected. The multiple window spatial registration errors obtained by the 133Ba method showed excellent reproducibility (standard deviation < 0.07 mm). The values were compared with the results from the NEMA procedure obtained at the same locations and showed small differences with a correlation coefficient of 0.51 (p < 0.05). In addition, the 133Ba point source method proved to be much easier to use. A Bland-Altman analysis showed that the 133Ba and the 67Ga Method can be used interchangeably.
Conclusion
The 133Ba point source method measures the multiple window spatial registration error with essentially the same accuracy as the NEMA-recommended procedure, but is easier and safer to use and has the potential to replace the current standard procedure.
doi:10.1186/1756-6649-8-6
PMCID: PMC2615416  PMID: 19068107

Results 1-8 (8)