Olivier Caselles

The retrospective binning method improves the consistency of phase binning in respiratory-gated PET/CT

This study assesses the accuracy of prospective phase-gated PET/CT data binning and presents a retrospective data binning method that improves image quality and consistency. Respiratory signals from 17 patients who underwent 4D PET/CT were analysed to evaluate the reproducibility of temporal triggers used for the standard phase-based gating method. Breathing signals were reprocessed to implement retrospective PET data binning. The mean and standard deviation of time lags between automatic triggers provided by the Real-time Position Management (RPM, Varian) gating device and inhalation peaks derived from respiratory curves were computed for each patient. The total number of respiratory cycles available for 4D PET/CT according to the binning mode (prospective versus retrospective) was compared. The maximum standardized uptake value (SUV(max)), biological tumour volume (BTV) and tumour trajectory measures were determined from the PET/CT images of five patients. Compared to retrospective binning (RB), prospective gating approach led to (i) a significant loss in breathing cycles (15%) and (ii) the inconsistency of data binning due to temporal dispersion of triggers (average 396 ms). Consequently, tumour characterization could be impacted. In retrospective mode, SUV(max) was up to 27% higher, where no significant difference appeared in BTV. In addition, prospective mode gave an inconsistent spatial location of the tumour throughout the bins. Improved consistency with breathing patterns and greater motion amplitude of the tumour centroid were observed with retrospective mode. The detection of the tumour motion and trajectory was improved also for small temporal dispersion of triggers. This study shows that the binning mode could have a significant impact on 4D PET images. The consistency of triggers with breathing signals should be checked before clinical use of gated PET/CT images, and our RB method improves 4D PET/CT image quantification.

Preclinical and Clinical Evidence that Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography with Computed Tomography Is a Reliable Tool for the Detection of Early Molecular Responses to Erlotinib in Head and Neck Cancer

Purpose: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[18F]fluoro-d-glucose positron emission tomography with computed tomography (18FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity. Experimental Design: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in 18FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib. Then, the pathologic and morphologic changes and the 18FDG-PET/CT uptake before and after erlotinib exposure in patients were analyzed. Results: Erlotinib strongly inhibited extracellular signal-regulated kinase-1/2 (ERK-1/2) phosphorylation both in the preclinical models and in patients. Western blotting, immunofluorescence, and immunohistochemistry showed that erlotinib did not modify Glut-1 expression at the protein level either in cell line models or in tumor tissue from mouse xenografts or in patients. Phospho-ERK-1/2 inhibition was associated with a reduction in 18FDG uptake in animal and human tumors. The biological volume was more accurate than the standardized uptake value for the evaluation of the molecular responses. Conclusion: These results show that the 18FDG-PET/CT response is a reliable surrogate marker of the effects of erlotinib in head and neck carcinoma. Clin Cancer Res; 16(17); 4434–45. ©2010 AACR.

A new respiratory gating device to improve 4D PET/CT

PURPOSE Respiratory motion creates artifacts in positon emission tomography with computed tomography (PET/CT) images especially for lung tumors, and can alter diagnosis. To account for motion effects, respiratory gating techniques have been developed. However, the lack of measures strongly correlated with tumor motion limits their accuracy. The authors developed a real-time pneumotachograph device (SPI) allowing to sort PET and CT images depending on lung volumes. METHODS The performance of this innovative respiratory tracking system was characterized and compared to a standard system. Our experimental setup consisted in a movable platform and a thorax phantom with six fillable spheres simulating lung tumors. The accuracy of SPI to detect inhalation peaks was also determined on volunteers. A comparison with the real-time position management (RPM) device, that relies on abdominal height measurement, was then investigated. RESULTS Experiments showed a high accuracy of the measured signal compared to the input signal (R = 0.88 to 0.99), and of the detection of the inhalation peaks (error of 0.1 +/- 5.8 ms) necessary for prospective binning mode. Activity recovery coefficient was improved (until +39%) and the smearing effect was reduced (until 2.74 times lower) with SPI compared to ungated PET/CT acquisition. The spatial distribution of activity in spheres was similar for 4D PET gated with SPI and RPM. Significant improvement of the binning stability and matching between PET and CT were highlighted for irregular breathing patterns with SPI. CONCLUSIONS SPI is an innovative device that provides better binning performance than the current gating device on phantom experiments. Future works will focus on patients where the authors expect a significant improvement of specificity and sensitivity of PET/CT examinations.

Automatic segmentation of breast MR images through a Markov random field statistical model.

An algorithm dedicated to automatic segmentation of breast magnetic resonance images is presented in this paper. Our approach is based on a pipeline that includes a denoising step and statistical segmentation. The noise removal preprocessing relies on an anisotropic diffusion scheme, whereas the statistical segmentation is conducted through a Markov random field model. The continuous updating of all parameters governing the diffusion process enables automatic denoising, and the partial volume effect is also addressed during the labeling step. To assess the relevance, the Jaccard similarity coefficient was computed. Experiments were conducted on synthetic data and breast magnetic resonance images extracted from a high-risk population. The relevance of the approach for the dataset is highlighted, and we demonstrate accuracy superior to that of traditional clustering algorithms. The results emphasize the benefits of both denoising guided by input data and the inclusion of spatial dependency through a Markov random field. For example, the Jaccard coefficient for the clinical data was increased by 114%, 109%, and 140% with respect to a K-means algorithm and, respectively, for the adipose, glandular and muscle and skin components. Moreover, the agreement between the manual segmentations provided by an experienced radiologist and the automatic segmentations performed with this algorithm was good, with Jaccard coefficients equal to 0.769, 0.756, and 0.694 for the above-mentioned classes.

Quality controls and delineation protocol of PET/CT gated acquisition in function of the movement amplitude, size of spheres and signal over background ratio

This study presents quality controls and segmentation tools for gated acquisition imaging of moving tumors. We study the effect of different amplitudes in a bin in function of sizes of spheres and signal to background ratios. Simple rules are then derived to establish which bins are appropriate to quantify tumor activity and to delineate volume. Finally the threshold technics for gated acquisition exams are discussed in function of the different parameters. Our experimental setup consisted of a movable platform, a thorax phantom with 6 fillable spheres and a real time position management device allowing to synchronize the PET/CT image with movement. The spheres were filled with F-Fluoro-2-deoxy-glucose and the activity in the tank was adjusted to obtain signal to background ratios from 3.5 to 20 (228 combinations of experimental parameters were studied). Maximal activity, optimal threshold and elongation of the sphere images between static and moving tumors were then compared with our own matlab program. Significant changes had appearing for movement superior to 7.5 mm in a bin leading to an activity decrease, an increase of the optimal threshold and an elongation in the movement direction. These effects were accentuated for low SBR and a sphere diameter inferior to 20 mm. The optimal threshold value was around 35% for large spheres and high SBR. This value increase when the sphere size and the SBR decrease. We then deduce from our measurements the relevant parameters for the delineation procedure. In conclusion, the effect of movement were successfully quantified in function of the sphere size, SBR and movement in a bin. Calibration threshold curves are now available in a clinical routine used for gated acquisitions.

ACCURATE PET-PET REGISTRATION TO ASSESS LUNG TUMOR EVOLUTION

Monitoring lung tumors necessitates precise registration of PET images acquired at different stages of a therapy. Existing direct registration methods try to match images leading to distorting the tumor. Inaccurate medical decisions would follow. This paper contributes to solving this problem. The proposed method consists of an indirect registration that takes three different stages. First, multimodal registration of pairs of CT and PET images is performed. Second, CT images are registered to estimate anatomical deformations. Third, the obtained transformation serves for the reconstruction of the PET moving image. The result is a pair of comparable PET images that can be analyzed to assess the actual evolution of the disease. The method has been validated using two types of experiments: phantoms and simulated tumors with synthetic deformations. The paper shows results of these experiments. They prove the validity of the approach and the accuracy of the reconstruction.

Comparison of an alternative and existing binning methods to reduce the acquisition duration of 4D PET/CT.

PURPOSE Respiratory motion is a source of artifacts that reduce image quality in PET. Four dimensional (4D) PET/CT is one approach to overcome this problem. Existing techniques to limiting the effects of respiratory motions are based on prospective phase binning which requires a long acquisition duration (15-25 min). This time is uncomfortable for the patients and limits the clinical exploitation of 4D PET/CT. In this work, the authors evaluated an existing method and an alternative retrospective binning method to reduce the acquisition duration of 4D PET/CT. METHODS The authors studied an existing mixed-amplitude binning (MAB) method and an alternative binning method by mixed-phases (MPhB). Before implementing MPhB, they analyzed the regularity of the breathing patterns in patients. They studied the breathing signal drift and missing CT slices that could be challenging for implementing MAB. They compared the performance of MAB and MPhB with current binning methods to measure the maximum uptake, internal volume, and maximal range of tumor motion. RESULTS MPhB can be implemented depending on an optimal phase (in average, the exhalation peak phase -4.1% of the entire breathing cycle duration). Signal drift of patients was in average 35% relative to the breathing amplitude. Even after correcting this drift, MAB was feasible in 4D CT for only 64% of patients. No significant differences appeared between the different binning methods to measure the maximum uptake, internal volume, and maximal range of tumor motion. The authors also determined the inaccuracies of MAB and MPhB to measure the maximum amplitude of tumor motion with three bins (less than 3 mm for movement inferior to 12 mm, up to 6.4 mm for a 21 mm movement). CONCLUSIONS The authors proposed an alternative binning method by mixed-phase binning that halves the acquisition duration of 4D PET/CT. Mixed-amplitude binning was challenging because of signal drift and missing CT slices. They showed that more than three bins were necessary for a more accurate measurement of the maximum amplitude of the tumor motion. However, the current 4D-CT technology limits the increase of the number of bins in 4D PET/CT because of missing CT slices. One can reconstruct 4D PET images with more bins but without attenuation/scatter correction.

Indirect PET-PET image registration to monitor lung cancer tumor

This paper deals with registering 3D PET images in order to monitor lung tumor evolution. Registering directly two PET images, taken at different stages of a cancer therapy, leads to deforming the tumor of the moving image to take the shape of the fixed image, loosing the tumor evolution information. This results in aberrant medical diagnosis. In order to solve this problem, we propose an indirect registration method that consists of processing pairs of CT-PET images. The CT images acquired at each stage are first registered to estimate anatomical transformations. The free-form deformation obtained is then applied to the corresponding PET images. The reconstructed PET images can be compared and used to monitor the tumor. The volume ratio and radiation density are calculated to assess the evolution of the tumor and evaluate the effectiveness of a therapy. The proposed iconic registration method is based on a B-Spline deformable model and mutual information. Two approaches have been used to validate the proposed method. First, we used phantoms to simulate the evolution of a tumor. The second approach consisted of simulating a tumor within real images. Quantitative measures show that our registration method keeps invariant volume and density distribution ratios of the tumor within PET images. This leads to improved tumor localisation and better evaluation of the efficiency of therapies.

Clinical outcomes 1 year after empiric : real life experience and predictive factors of functional response131: real life experience and predictive factors of functional responsei therapy for hyperthyroid disorders: real life experience and predictive factors of functional response

Radioiodine is a therapeutic option in Europe for Graves’ disease (GD) and toxic multinodular goiter (MNG). Purpose To compare empiric and calculated 131I activities using 2013 EANM recommendations. To look for predictive factors of therapeutic response to an empiric activity of 131I. To assess clinical situations favoring calculated treatment modalities. Patients and methods Prospective monocentric study of clinical outcomes at 1 year follow-up in 86 patients with GD and MNG who received empiric 131I therapeutic activities (348–939 MBq). Differences between empiric and calculated activities were confronted to clinical outcomes. Physicians were not aware of the calculated activity at the time of prescription. Results One year after treatment, 9% (5/57) of GD patients and 7% (2/29) of MNG patients were still in a hyperthyroid state. Thyroid volume was reduced by 67% for GD and by 50% for MNG. In GD, empiric 131I activities were higher than calculated ones (564±131 vs. 316±319 MBq, P<0.001) in 93% (53/57) of patients. Pretherapeutic thyroid volume (>26 ml for GD; >40 ml for MNG) was associated with persistent hyperthyroidism. Conclusion Empirically administered 131I for GD and MNG was associated with very high efficacy in thyroid function control and no side effects. Thyroid volume reduction did not preclude treatment efficacy. Activity calculation could be a useful method for treating patients with GD and thyroid volumes higher than 26 ml or patients with MNG and thyroid volumes higher than 40 ml. A selective approach based on pretherapeutic thyroid volume and radioiodine biokinetics might improve treatment success.

MO‐D‐141‐11: Registration of Breast Magnetic Resonance Imaging and X‐Ray Mammography Through a Biomechanical Model Based On Clinical Data and a Finite Element Method

PURPOSE Overcoming the drawbacks of x-ray mammography and magnetic resonance imaging (MRI) by fusing the information in order to assist clinicians in the task of early detection of breast cancer. METHODS A detailed 3D computer-generated breast phantom based on empirical data extracted from breast MRI was constructed for each patient. To achieve this goal, MRI data were classified into the different components of breast tissues (glandular, adipose, skin and eventually tumor) using a semi-automated segmentation algorithm based on voxel intensity. Then, a geometrical model of the breast was constructed through the isosurfaces of this segmented volume. In order to perform a study on breast deformation using the finite element method, the geometrical model was automatically meshed into tetrahedral elements and material properties were assigned to the different kinds of breast tissues. To represent the large deformation of breast during a mammography exam, a neo-Hookean hyperelastic model was chosen to describe the constitutive relations of breast tissues, and the compression was simulated using a stiff plate model. After compressing the phantom, mammograms were simulated based on the deformed configuration. During this step, a parametric optimization of the model was conducted (mesh refinement, mechanical properties and friction coefficient). RESULTS Small variations of the model parameters strongly influence the deformation and modify significantly the resultant simulated images. During the optimization process, both a better conservation of details and a convergence toward a distribution of components were observed for finer meshes, whereas the friction coefficient affects mostly the skin deformation. CONCLUSION The phantom developed in this study allows the modeling of large deformations through the use of the finite element method, and also allows the simulation of mammographic images containing high-resolution details. Moreover, this phantom combines flexibility and realism, and can be used for multimodality imaging research but also for clinical performance optimization.