Longitudinal, intermodality registration of quantitative breast PET and MRI data acquired before and during neoadjuvant chemotherapy: preliminary results.
ABSTRACT: The authors propose a method whereby serially acquired DCE-MRI, DW-MRI, and FDG-PET breast data sets can be spatially and temporally coregistered to enable the comparison of changes in parameter maps at the voxel level.First, the authors aligned the PET and MR images at each time point rigidly and nonrigidly. To register the MR images longitudinally, the authors extended a nonrigid registration algorithm by including a tumor volume-preserving constraint in the cost function. After the PET images were aligned to the MR images at each time point, the authors then used the transformation obtained from the longitudinal registration of the MRI volumes to register the PET images longitudinally. The authors tested this approach on ten breast cancer patients by calculating a modified Dice similarity of tumor size between the PET and MR images as well as the bending energy and changes in the tumor volume after the application of the registration algorithm.The median of the modified Dice in the registered PET and DCE-MRI data was 0.92. For the longitudinal registration, the median tumor volume change was -0.03% for the constrained algorithm, compared to -32.16% for the unconstrained registration algorithms (p = 8 × 10(-6)). The medians of the bending energy were 0.0092 and 0.0001 for the unconstrained and constrained algorithms, respectively (p = 2.84 × 10(-7)).The results indicate that the proposed method can accurately spatially align DCE-MRI, DW-MRI, and FDG-PET breast images acquired at different time points during therapy while preventing the tumor from being substantially distorted or compressed.
Project description:OBJECTIVES:To investigate the reliability of simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI)-derived biomarkers using semi-automated Gaussian mixture model (GMM) segmentation on PET images, against conventional manual tumor segmentation on dynamic contrast-enhanced (DCE) images. MATERIALS AND METHODS:Twenty-four breast cancer patients underwent PET/MRI (following 18F-fluorodeoxyglucose (18F-FDG) injection) at baseline and during neoadjuvant treatment, yielding 53 data sets (24 untreated, 29 treated). Two-dimensional tumor segmentation was performed manually on DCE-MRI images (manual DCE) and using GMM with corresponding PET images (GMM-PET). Tumor area and mean apparent diffusion coefficient (ADC) derived from both segmentation methods were compared, and spatial overlap between the segmentations was assessed with Dice similarity coefficient and center-of-gravity displacement. RESULTS:No significant differences were observed between mean ADC and tumor area derived from manual DCE segmentation and GMM-PET. There were strong positive correlations for tumor area and ADC derived from manual DCE and GMM-PET for untreated and treated lesions. The mean Dice score for GMM-PET was 0.770 and 0.649 for untreated and treated lesions, respectively. DISCUSSION:Using PET/MRI, tumor area and mean ADC value estimated with a GMM-PET can replicate manual DCE tumor definition from MRI for monitoring neoadjuvant treatment response in breast cancer.
Project description:Tumor hypoxia is a major cause of radiation resistance, often present in various solid tumors. Dynamic [18 F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumor hypoxia. Comprehensive characterization of tumor microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition. The aim of this work was to explore the correlation between the FMISO-PET and DCE-MRI kinetic parameters.This study was done on head and neck cancer patients (N = 6), who were imaged dynamically with FMISO-PET and DCE-MRI on the same day. Images were registered and analyzed for kinetics on a voxel basis. FMISO-PET images were analyzed with the two-tissue compartment three rate-constant model. Additionally, tumor-to-muscle ratio (TMR) maps were evaluated. DCE-MRI was analyzed with the extended Tofts model. Voxel-wise Pearson's coefficients were calculated for each patient to assess pairwise parameter correlations.Median correlations between FMISO uptake parameters and DCE-MRI kinetic parameters varied across the parameter pairs in the range from -0.05 to 0.71. The highest median correlation of r = 0.71 was observed for the pair Vb -vp , while the K1 -Ktrans median correlation was r = 0.45. Median correlation coefficients for the K1 -vp and the Ki -Ktrans pairs were r = 0.42 and r = 0.32, respectively. Correlations between FMISO uptake rate parameter Ki and DCE-MRI kinetic parameters varied substantially across the patients, whereas correlations between the FMISO and DCE-MRI vascular parameters were consistently high. Median TMR-K1 and TMR-Ktrans correlations were r = 0.52 and r = 0.46, respectively, but varied substantially across the patients.Based on this clinical evidence, we can conclude that the vascular fraction parameters obtained through DCE-MRI kinetic analysis or FMISO kinetic analysis measure the same biological property, while other kinetic parameters are unrelated. These results might be useful in the design of future clinical trials involving FMISO-PET/DCE-MR multimodality imaging for the assessment of tumor microenvironment.
Project description:We present an approach for concurrent reconstruction of respiratory motion-compensated abdominal dynamic contrast-enhanced (DCE)-MRI and PET data in an integrated PET/MR scanner. The MR and PET reconstructions share the same motion vector fields derived from radial MR data; the approach is robust to changes in respiratory pattern and does not increase the total acquisition time. Methods: PET and DCE-MRI data of 12 oncologic patients were simultaneously acquired for 6 min on an integrated PET/MR system after administration of 18F-FDG and gadoterate meglumine. Golden-angle radial MR data were continuously acquired simultaneously with PET data and sorted into multiple motion phases on the basis of a respiratory signal derived directly from the radial MR data. The resulting multidimensional dataset was reconstructed using a compressed sensing approach that exploits sparsity among respiratory phases. Motion vector fields obtained using the full 6-min (MC6-min) and only the last 1 min (MC1-min) of data were incorporated into the PET reconstruction to obtain motion-corrected PET images and in an MR iterative reconstruction algorithm to produce a series of motion-corrected DCE-MR images (moco_GRASP). The motion-correction methods (MC6-min and MC1-min) were evaluated by qualitative analysis of the MR images and quantitative analysis of SUVmax and SUVmean, contrast, signal-to-noise ratio (SNR), and lesion volume in the PET images. Results: Motion-corrected MC6-min PET images demonstrated 30%, 23%, 34%, and 18% increases in average SUVmax, SUVmean, contrast, and SNR and an average 40% reduction in lesion volume with respect to the non-motion-corrected PET images. The changes in these figures of merit were smaller but still substantial for the MC1-min protocol: 19%, 10%, 15%, and 9% increases in average SUVmax, SUVmean, contrast, and SNR; and a 28% reduction in lesion volume. Moco_GRASP images were deemed of acceptable or better diagnostic image quality with respect to conventional breath-hold Cartesian volumetric interpolated breath-hold examination acquisitions. Conclusion: We presented a method that allows the simultaneous acquisition of respiratory motion-corrected diagnostic quality DCE-MRI and quantitatively accurate PET data in an integrated PET/MR scanner with negligible prolongation in acquisition time compared with routine PET/DCE-MRI protocols.
Project description:The goal of this work was to investigate the effects of MRI surface coils on attenuation-corrected PET emission data. The authors studied the cases where either an MRI or a CT scan would be used to provide PET attenuation correction (AC). Combined MR/PET scanners that use the MRI for PET AC (MR-AC) face the challenge of absent surface coils in MR images and thus cannot directly account for attenuation in the coils. Combining MR and PET images could be achieved by transporting the subject on a stereotactically registered table between independent MRI and PET scanners. In this case, conventional PET CT-AC methods could be used. A challenge here is that high atomic number materials within MR coils cause artifacts in CT images and CT based AC is typically not validated for coil materials.The authors evaluated PET artifacts when MR coils were absent from AC data (MR-AC), or when coil attenuation was measured by CT scanning (CT-AC). They scanned PET phantoms with MR surface coils on a clinical PET/CT system and used CT-AC to reconstruct PET data. The authors then omitted the coil from the CT-AC image to mimic the MR-AC scenario. Images were acquired using cylinder and anthropomorphic phantoms. They evaluated and compared the following five scenarios: (1) A uniform cylinder phantom and head coil scanned and reconstructed using CT-AC; (2) similar emission data (with head coil present) were reconstructed without the head coil in the AC data; (3) the same cylinder scanned without the head coil present (reference scan); (4) a PET torso phantom with a full MR torso coil present in both PET and CT; (5) only half of the separable torso coil present in the PET/CT acquisition. The authors also performed analytic simulations of the first three scenarios.Streak artifacts were present in CT images containing MR surface coils due to metal components. These artifacts persisted after the CT images were converted for PET AC. The artifacts were significantly reduced when half of the separable coil was removed during the scan. CT scans tended to over-estimate the linear attenuation coefficient (micro) of the metal components when using conventional methods for converting from CT number to micro(511 keV). Artifacts were visible outside the phantom in some of the PET emission images, corresponding to the MRI coil geometry. However, only subtle artifacts were apparent in the emission images inside the phantoms. On the other hand, the PET emission image quantitative accuracy was significantly affected: the activity was underestimated by 19% when AC did not include the head coil, and overestimated by 28% when the CT-AC included the head coil.The presence of MR coils during PET or PET/CT scanning can cause subtle artifacts and potentially important quantification errors. Alternative CT techniques that mitigate artifacts should be used to improve AC accuracy. When possible, removing segments of an MR coil prior to the PET/CT exam is recommended. Further, MR coils could be redesigned to reduce artifacts by rearranging placement of the most attenuating materials.
Project description:<h4>Objectives</h4>To decipher the correlations between PET and DCE kinetic parameters in non-small-cell lung cancer (NSCLC), by using voxel-wise analysis of dynamic simultaneous [18F]FDG PET-MRI.<h4>Material and methods</h4>Fourteen treatment-naïve patients with biopsy-proven NSCLC prospectively underwent a 1-h dynamic [18F]FDG thoracic PET-MRI scan including DCE. The PET and DCE data were normalized to their corresponding T<sub>1</sub>-weighted MR morphological space, and tumors were masked semi-automatically. Voxel-wise parametric maps of PET and DCE kinetic parameters were computed by fitting the dynamic PET and DCE tumor data to the Sokoloff and Extended Tofts models respectively, by using in-house developed procedures. Curve-fitting errors were assessed by computing the relative root mean square error (rRMSE) of the estimated PET and DCE signals at the voxel level. For each tumor, Spearman correlation coefficients (r<sub>s</sub>) between all the pairs of PET and DCE kinetic parameters were estimated on a voxel-wise basis, along with their respective bootstrapped 95% confidence intervals (n = 1000 iterations).<h4>Results</h4>Curve-fitting metrics provided fit errors under 20% for almost 90% of the PET voxels (median rRMSE = 10.3, interquartile ranges IQR = 8.1; 14.3), whereas 73.3% of the DCE voxels showed fit errors under 45% (median rRMSE = 31.8%, IQR = 22.4; 46.6). The PET-PET, DCE-DCE, and PET-DCE voxel-wise correlations varied according to individual tumor behaviors. Beyond this wide variability, the PET-PET and DCE-DCE correlations were mainly high (absolute r<sub>s</sub> values > 0.7), whereas the PET-DCE correlations were mainly low to moderate (absolute r<sub>s</sub> values < 0.7). Half the tumors showed a hypometabolism with low perfused/vascularized profile, a hallmark of hypoxia, and tumor aggressiveness.<h4>Conclusion</h4>A dynamic "one-stop shop" procedure applied to NSCLC is technically feasible in clinical practice. PET and DCE kinetic parameters assessed simultaneously are not highly correlated in NSCLC, and these correlations showed a wide variability among tumors and patients. These results tend to suggest that PET and DCE kinetic parameters might provide complementary information. In the future, this might make PET-MRI a unique tool to characterize the individual tumor biological behavior in NSCLC.
Project description:INTRODUCTION:Preclinical in vivo imaging requires precise and reproducible delineation of brain structures. Manual segmentation is time consuming and operator dependent. Automated segmentation as usually performed via single atlas registration fails to account for anatomo-physiological variability. We present, evaluate, and make available a multi-atlas approach for automatically segmenting rat brain MRI and extracting PET activies. METHODS:High-resolution 7T 2DT2 MR images of 12 Sprague-Dawley rat brains were manually segmented into 27-VOI label volumes using detailed protocols. Automated methods were developed with 7/12 atlas datasets, i.e. the MRIs and their associated label volumes. MRIs were registered to a common space, where an MRI template and a maximum probability atlas were created. Three automated methods were tested: 1/registering individual MRIs to the template, and using a single atlas (SA), 2/using the maximum probability atlas (MP), and 3/registering the MRIs from the multi-atlas dataset to an individual MRI, propagating the label volumes and fusing them in individual MRI space (propagation & fusion, PF). Evaluation was performed on the five remaining rats which additionally underwent [18F]FDG PET. Automated and manual segmentations were compared for morphometric performance (assessed by comparing volume bias and Dice overlap index) and functional performance (evaluated by comparing extracted PET measures). RESULTS:Only the SA method showed volume bias. Dice indices were significantly different between methods (PF>MP>SA). PET regional measures were more accurate with multi-atlas methods than with SA method. CONCLUSIONS:Multi-atlas methods outperform SA for automated anatomical brain segmentation and PET measure's extraction. They perform comparably to manual segmentation for FDG-PET quantification. Multi-atlas methods are suitable for rapid reproducible VOI analyses.
Project description:In this study, PET heterogeneity was combined with functional MRI techniques to refine the prediction of prognosis in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC).A total of 124 patients with primary advanced OHSCC who underwent pretreatment 18F-FDG PET/CT, dynamic contrast-enhanced MR imaging (DCE-MRI), and diffusion-weighted MR imaging (DWI) were enrolled. Conventional and heterogeneity parameters from 18F-FDG PET as well as perfusion parameters from DCE-MRI and diffusion parameter from DWI of primary tumors were analyzed in relation to recurrence-free survival (RFS) and overall survival (OS).Multivariate analysis identified hypopharyngeal tumors (P = 0.038), alcohol drinking (P = 0.006), K trans ? 0.5512 (P = 0.017), and K ep ? 0.8872 (P = 0.005) as adverse prognostic factors for RFS. Smoking (p = 0.009), K trans ? 0.5512 (P = 0.0002), K ep ? 0.8872 (P = 0.004), and the PET heterogeneity parameter uniformity ? 0.00381 (P = 0.028) were independent predictors of poor OS. The combination of PET uniformity with DCE-MRI parameters and smoking allowed distinguishing four prognostic groups, with 3-year OS rates of 100%, 76.6%, 57.4%, and 7.1%, respectively (P < 0.0001). This prognostic system appeared superior to both the TNM staging system (P = 0.186) and the combination of conventional PET parameters with DCE-MRI (P = 0.004).Multiparametric imaging based on PET heterogeneity and DCE-MRI parameters combined with clinical risk factors is superior to the concomitant use of functional MRI coupled with conventional PET parameters. This approach may improve the prognostic stratification of OHSCC patients.
Project description:<h4>Background</h4>Inflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers.<h4>Methods</h4>Nineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic 11C-(R)-PK11195 PET and a comprehensive MR protocol, including high temporal resolution DCE-MRI in 15 patients. An intertumor comparison of 11C-(R)-PK11195 binding potential (BPND) and DCE-MRI derived vascular biomarkers (Ktrans, vp, ve) across the 3 different tumor growth cohorts was undertaken. Tissue of 8 tumors was examined with immunohistochemistry markers for inflammation (Iba1), neoplastic cells (S-100 protein), vessels (CD31), the PK11195 target translocator protein (TSPO), fibrinogen for vascular permeability, and proliferation (Ki-67). Results were correlated with PET and DCE-MRI data.<h4>Results</h4>Compared with static tumors, growing VS displayed significantly higher mean 11C-(R)-PK11195 BPND (-0.07 vs 0.47, P = 0.020), and higher mean tumor Ktrans (0.06 vs 0.14, P = 0.004). Immunohistochemistry confirmed the imaging findings and demonstrated that TSPO is predominantly expressed in macrophages. Within growing VS, macrophages rather than tumor cells accounted for the majority of proliferating cells.<h4>Conclusion</h4>We present the first in vivo imaging evidence of increased inflammation within growing sporadic VS. Our results demonstrate that 11C-(R)-PK11195 specific binding and DCE-MRI derived parameters can be used as imaging biomarkers of inflammation and vascular permeability in this tumor group.
Project description:We present a novel technique for accurate whole-body attenuation correction in the presence of metallic endoprosthesis, on integrated non-time-of-flight (non-TOF) PET/MRI scanners. The proposed implant PET-based attenuation map completion (IPAC) method performs a joint reconstruction of radioactivity and attenuation from the emission data to determine the position, shape, and linear attenuation coefficient (LAC) of metallic implants. Methods: The initial estimate of the attenuation map was obtained using the MR Dixon method currently available on the Siemens Biograph mMR scanner. The attenuation coefficients in the area of the MR image subjected to metal susceptibility artifacts are then reconstructed from the PET emission data using the IPAC algorithm. The method was tested on 11 subjects presenting 13 different metallic implants, who underwent CT and PET/MR scans. Relative mean LACs and Dice similarity coefficients were calculated to determine the accuracy of the reconstructed attenuation values and the shape of the metal implant, respectively. The reconstructed PET images were compared with those obtained using the reference CT-based approach and the Dixon-based method. Absolute relative change (aRC) images were generated in each case, and voxel-based analyses were performed. Results: The error in implant LAC estimation, using the proposed IPAC algorithm, was 15.7% ± 7.8%, which was significantly smaller than the Dixon- (100%) and CT- (39%) derived values. A mean Dice similarity coefficient of 73% ± 9% was obtained when comparing the IPAC- with the CT-derived implant shape. The voxel-based analysis of the reconstructed PET images revealed quantification errors (aRC) of 13.2% ± 22.1% for the IPAC- with respect to CT-corrected images. The Dixon-based method performed substantially worse, with a mean aRC of 23.1% ± 38.4%. Conclusion: We have presented a non-TOF emission-based approach for estimating the attenuation map in the presence of metallic implants, to be used for whole-body attenuation correction in integrated PET/MR scanners. The Graphics Processing Unit implementation of the algorithm will be included in the open-source reconstruction toolbox Occiput.io.