Toward PET/MRI as one-stop shop for radiotherapy planning in cervical cancer patients.

BACKGROUND: Radiotherapy (RT) planning for cervical cancer patients entails the acquisition of both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Further, molecular imaging by Positron Emission Tomography (PET) could contribute to target volume delineation as well as treatment response monitoring. The objective of this study was to investigate the feasibility of a PET/MRI-only RT planning workflow of patients with cervical cancer. This includes attenuation correction (AC) of MRI hardware and dedicated positioning equipment as well as evaluating MRI-derived synthetic CT (sCT) of the pelvic region for positioning verification and dose calculation to enable a PET/MRI-only setup. MATERIAL AND METHODS: 16 patients underwent PET/MRI using a dedicated RT setup after the routine CT (or PET/CT), including eight pilot patients and eight cervical cancer patients who were subsequently referred for RT. Data from 18 patients with gynecological cancer were added for training a deep convolutional neural network to generate sCT from Dixon MRI. The mean absolute difference between the dose distributions calculated on sCT and a reference CT was measured in the RT target volume and organs at risk. PET AC by sCT and a reference CT were compared in the tumor volume. RESULTS: All patients completed the examination. sCT was inferred for each patient in less than 5 s. The dosimetric analysis of the sCT-based dose planning showed a mean absolute error (MAE) of 0.17 ± 0.12 Gy inside the planning target volumes (PTV). PET images reconstructed with sCT and CT had no significant difference in quantification for all patients. CONCLUSIONS: These results suggest that multiparametric PET/MRI can be successfully integrated as a one-stop-shop in the RT workflow of patients with cervical cancer.

Integrated PET/MR.

Integrated whole-body PET/MR hybrid imaging combines excellent soft tissue contrast and various functional imaging parameters provided by MR with high sensitivity and quantification of radiotracer metabolism provided by positron emission tomography (PET). While clinical evaluation now is under way, integrated PET/MR demands for new technologies and innovative solutions, currently subject to interdisciplinary research. Attenuation correction of human soft tissues and of hardware components has to be MR-based to maintain quantification of PET imaging because computed tomography (CT) attenuation information is missing. This brings up the question of how to provide bone information with MR imaging. The limited field-of-view in MR imaging leads to truncations in body imaging and MR-based attenuation correction. Another research field is the implementation of motion correction technologies to correct for breathing and cardiac motion in view of the relatively long PET data acquisition times. Initial clinical applications of integrated PET/MR in oncology, neurology, pediatric oncology, and cardiovascular disease are highlighted. The hybrid imaging workflow here has to be tailored to the clinical indication to maximize diagnostic information while minimizing acquisition time. PET/MR introduces new artifacts that need special observation and innovative solutions for correction. Finally, the rising need for appropriate phantoms and standardization efforts in PET/MR hybrid imaging is discussed.

Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients.

Background: In glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is known about the impact of different types of damage on the fiber architecture of the affected white matter. Patients and methods: This study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group. Results: Lesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score. Conclusions: These results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance status due to the larger volume affected.

Performance of Multiparametric Functional Imaging and Texture Analysis in Predicting Synchronous Metastatic Disease in Pancreatic Ductal Adenocarcinoma Patients by Hybrid PET/MR: Initial Experience.

Objectives: To assess the imaging biomarkers of glucose metabolic activity and diffusion-weighted imaging (DWI) derived from pretreatment integrated 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET/MR) imaging as potential predictive factors of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We retrospectively included 17 consecutive patients with pathologically confirmed PDAC by pretreatment 18F-FDG PET/MR. The study subjects were divided into a non-metastatic group (M0, six cases) and a metastatic group (M1, 11 cases). The 18F-FDG PET/MR images were reviewed independently by two board certificated nuclear medicine physicians and one radiologist. Conventional characteristics and quantitative parameters from both PET and apparent diffusion coefficient (ADC) were assessed. The texture features were extracted from LIFEx packages (www.lifexsoft.org), and a 3D tumor volume of interest was manually drawn on fused PET/ADC images. Chi-square tests, independent-samples t-tests and Mann-Whitney U-tests were used to compare the differences in single parameters between the two groups. A logistic regression analysis was performed to determine independent predictors. A receiver operating characteristic (ROC) curve analysis was performed to assess the discriminatory power of the selected parameters. Correlations between metabolic parameters and ADC features were calculated with Spearman's rank correlation coefficient test. Results: For conventional parameters, univariable analysis demonstrated that the M1 group had a significantly larger size and a higher peak of standardized uptake value (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) than those of the M0 group (p < 0.05 for all). TLG remained significant predictor in the multivariable analysis, but there were no significant differences for the area under the ROC curve (AUC) among the four conventional features in differential diagnoses (p > 0.05 for all). For the texture features, there were four features from the PET image and 13 from the ADC map that showed significant differences between the two groups. Multivariate analysis indicated that one feature from PET and three from the ADC were significant predictors. TLG was associated with ADC-GLRLM_GLNU (r = 0.659), ADC-GLRLM_LRHGE (r = 0.762), and PET-GLRLM_LRHGE (r = 0.806). Conclusions: Multiple parameters and texture features of primary tumors from 18F-FDG PET/MR images maybe reliable biomarkers to predict synchronous metastatic disease for the pretreatment PDAC.

Impact of Point-Spread Function Modeling on PET Image Quality in Integrated PET/MR Hybrid Imaging.

UNLABELLED: The aim of this study was to systematically assess the quantitative and qualitative impact of including point-spread function (PSF) modeling into the process of iterative PET image reconstruction in integrated PET/MR imaging. METHODS: All measurements were performed on an integrated whole-body PET/MR system. Three substudies were performed: an (18)F-filled Jaszczak phantom was measured, and the impact of including PSF modeling in ordinary Poisson ordered-subset expectation maximization reconstruction on quantitative accuracy and image noise was evaluated for a range of radial phantom positions, iteration numbers, and postreconstruction smoothing settings; 5 representative datasets from a patient population (total n = 20, all oncologic (18)F-FDG PET/MR) were selected, and the impact of PSF on lesion activity concentration and image noise for various iteration numbers and postsmoothing settings was evaluated; and for all 20 patients, the influence of PSF modeling was investigated on visual image quality and number of detected lesions, both assessed by clinical experts. Additionally, the influence on objective metrics such as changes in SUVmean, SUVpeak, SUVmax, and lesion volume was assessed using the manufacturer-recommended reconstruction settings. RESULTS: In the phantom study, PSF modeling significantly improved activity recovery and reduced the image noise at all radial positions. This effect was measurable only at a high number of iterations (>10 iterations, 21 subsets). In the patient study, again, PSF increased the detected activity in the patient's lesions at concurrently reduced image noise. Contrary to the phantom results, the effect was notable already at a lower number of iterations (>1 iteration, 21 subsets). Lastly, for all 20 patients, when PSF and no-PSF reconstructions were compared, an identical number of congruent lesions was found. The overall image quality of the PSF reconstructions was rated better when compared with no-PSF data. The SUVs of the detected lesions with PSF were substantially increased in the range of 6%-75%, 5%-131%, and 5%-148% for SUVmean, SUVpeak, and SUVmax, respectively. A regression analysis showed that the relative increase in SUVmean/peak/max decreases with increasing lesion size, whereas it increases with the distance from the center of the PET field of view. CONCLUSION: In whole-body PET/MR hybrid imaging, PSF-based PET reconstructions can improve activity recovery and image noise, especially at lateral positions of the PET field of view. This has been demonstrated quantitatively in phantom experiments as well as in patient imaging, for which additionally an improvement of image quality could be observed.

Dixon Sequence with Superimposed Model-Based Bone Compartment Provides Highly Accurate PET/MR Attenuation Correction of the Brain.

UNLABELLED: Simultaneous PET/MR of the brain is a promising technology for characterizing patients with suspected cognitive impairment or epilepsy. Unlike CT, however, MR signal intensities do not correlate directly with PET photon attenuation correction (AC), and inaccurate radiotracer SUV estimation can limit future PET/MR clinical applications. We tested a novel AC method that supplements standard Dixon-based tissue segmentation with a superimposed model-based bone compartment. METHODS: We directly compared SUV estimation between MR-based AC and reference CT AC in 16 patients undergoing same-day PET/CT and PET/MR with a single (18)F-FDG dose for suspected neurodegeneration. Three Dixon-based MR AC methods were compared with CT: standard Dixon 4-compartment segmentation alone, Dixon with a superimposed model-based bone compartment, and Dixon with a superimposed bone compartment and linear AC optimized specifically for brain tissue. The brain was segmented using a 3-dimensional T1-weighted volumetric MR sequence, and SUV estimations were compared with CT AC for whole-image, whole-brain, and 91 FreeSurfer-based regions of interest. RESULTS: Modifying the linear AC value specifically for brain and superimposing a model-based bone compartment reduced the whole-brain SUV estimation bias of Dixon-based PET/MR AC by 95% compared with reference CT AC (P < 0.05), resulting in a residual -0.3% whole-brain SUVmean bias. Further, brain regional analysis demonstrated only 3 frontal lobe regions with an SUV estimation bias of 5% or greater (P < 0.05). These biases appeared to correlate with high individual variability in frontal bone thickness and pneumatization. CONCLUSION: Bone compartment and linear AC modifications result in a highly accurate MR AC method in subjects with suspected neurodegeneration. This prototype MR AC solution appears equivalent to other recently proposed solutions and does not require additional MR sequences and scanning time. These data also suggest that exclusively model-based MR AC approaches may be adversely affected by common individual variations in skull anatomy.

PET/MR imaging: current and future applications for cardiovascular disease.

PET and magnetic resonance (MR) imaging have each become essential tools in the workup and management of cardiac patients. Combined PET/MR systems have recently been developed, allowing for single-session imaging using both modalities. This new technology holds great promise for cardiac applications given the different, yet complementary, information each modality provides. Research in this area is still nascent, although early studies have been promising.

Whole-Body PET/MR Imaging: Quantitative Evaluation of a Novel Model-Based MR Attenuation Correction Method Including Bone.

UNLABELLED: In routine whole-body PET/MR hybrid imaging, attenuation correction (AC) is usually performed by segmentation methods based on a Dixon MR sequence providing up to 4 different tissue classes. Because of the lack of bone information with the Dixon-based MR sequence, bone is currently considered as soft tissue. Thus, the aim of this study was to evaluate a novel model-based AC method that considers bone in whole-body PET/MR imaging. METHODS: The new method ("Model") is based on a regular 4-compartment segmentation from a Dixon sequence ("Dixon"). Bone information is added using a model-based bone segmentation algorithm, which includes a set of prealigned MR image and bone mask pairs for each major body bone individually. Model was quantitatively evaluated on 20 patients who underwent whole-body PET/MR imaging. As a standard of reference, CT-based µ-maps were generated for each patient individually by nonrigid registration to the MR images based on PET/CT data. This step allowed for a quantitative comparison of all µ-maps based on a single PET emission raw dataset of the PET/MR system. Volumes of interest were drawn on normal tissue, soft-tissue lesions, and bone lesions; standardized uptake values were quantitatively compared. RESULTS: In soft-tissue regions with background uptake, the average bias of SUVs in background volumes of interest was 2.4% ± 2.5% and 2.7% ± 2.7% for Dixon and Model, respectively, compared with CT-based AC. For bony tissue, the -25.5% ± 7.9% underestimation observed with Dixon was reduced to -4.9% ± 6.7% with Model. In bone lesions, the average underestimation was -7.4% ± 5.3% and -2.9% ± 5.8% for Dixon and Model, respectively. For soft-tissue lesions, the biases were 5.1% ± 5.1% for Dixon and 5.2% ± 5.2% for Model. CONCLUSION: The novel MR-based AC method for whole-body PET/MR imaging, combining Dixon-based soft-tissue segmentation and model-based bone estimation, improves PET quantification in whole-body hybrid PET/MR imaging, especially in bony tissue and nearby soft tissue.

NEMA image quality phantom measurements and attenuation correction in integrated PET/MR hybrid imaging.

BACKGROUND: In integrated PET/MR hybrid imaging the evaluation of PET performance characteristics according to the NEMA standard NU 2-2007 is challenging because of incomplete MR-based attenuation correction (AC) for phantom imaging. In this study, a strategy for CT-based AC of the NEMA image quality (IQ) phantom is assessed. The method is systematically evaluated in NEMA IQ phantom measurements on an integrated PET/MR system. METHODS: NEMA IQ measurements were performed on the integrated 3.0 Tesla PET/MR hybrid system (Biograph mMR, Siemens Healthcare). AC of the NEMA IQ phantom was realized by an MR-based and by a CT-based method. The suggested CT-based AC uses a template µ-map of the NEMA IQ phantom and a phantom holder for exact repositioning of the phantom on the systems patient table. The PET image quality parameters contrast recovery, background variability, and signal-to-noise ratio (SNR) were determined and compared for both phantom AC methods. Reconstruction parameters of an iterative 3D OP-OSEM reconstruction were optimized for highest lesion SNR in NEMA IQ phantom imaging. RESULTS: Using a CT-based NEMA IQ phantom µ-map on the PET/MR system is straightforward and allowed performing accurate NEMA IQ measurements on the hybrid system. MR-based AC was determined to be insufficient for PET quantification in the tested NEMA IQ phantom because only photon attenuation caused by the MR-visible phantom filling but not the phantom housing is considered. Using the suggested CT-based AC, the highest SNR in this phantom experiment for small lesions (<= 13 mm) was obtained with 3 iterations, 21 subsets and 4 mm Gaussian filtering. CONCLUSION: This study suggests CT-based AC for the NEMA IQ phantom when performing PET NEMA IQ measurements on an integrated PET/MR hybrid system. The superiority of CT-based AC for this phantom is demonstrated by comparison to measurements using MR-based AC. Furthermore, optimized PET image reconstruction parameters are provided for the highest lesion SNR in NEMA IQ phantom measurements.

Radiotracer dose reduction in integrated PET/MR: implications from national electrical manufacturers association phantom studies.

UNLABELLED: With the replacement of ionizing CT by MR imaging, integrated PET/MR in selected clinical applications may reduce the overall patient radiation dose when compared with PET/CT. Further potential for radiotracer dose reduction, while maintaining PET image quality (IQ) in integrated PET/MR, may be achieved by increasing the PET acquisition duration to match the longer time needed for MR data acquisition. To systematically verify this hypothesis under controlled conditions, this dose-reduction study was performed using a standardized phantom following the National Electrical Manufacturers Association (NEMA) IQ protocol. METHODS: All measurements were performed on an integrated PET/MR whole-body hybrid system. The NEMA IQ phantom was filled with water and a total activity of 50.35 MBq of (18)F-FDG. The sphere-to-background activity ratio was 8:1. Multiple PET data blocks of 20-min acquisition time were acquired in list-mode format and were started periodically at multiples of the (18)F-FDG half-lives. Different sinograms (2, 4, 8, and 16 min in duration) were reconstructed. Attenuation correction of the filled NEMA phantom was performed using a CT-based attenuation map template. The attenuation-corrected PET images were then quantitatively evaluated following the NEMA IQ protocol, investigating contrast recovery, background variability, and signal-to-noise ratio. Image groups with half the activity and twice the acquisition time were evaluated. For better statistics, the experiment was repeated 3 times. RESULTS: Contrast recovery, background variability, and signal-to-noise ratio remained almost constant over 3 half-life periods when the decreasing radiotracer activity (100%, 50%, 25%, and 12.5%) was compensated by increasing acquisition time (2, 4, 8, and 16 min). The variation of contrast recovery over 3 half-life periods was small (-6% to +7%), with a mean variation of 2%, compared with the reference setting (100%, 2 min). The signal-to-noise ratio of the hot spheres showed only minor variations over 3 half-life periods (5%). Image readers could not distinguish subjective IQ between the different PET acquisition setups. CONCLUSION: An approach to reduce the injected radiotracer activity in integrated PET/MR imaging, while maintaining PET IQ, was presented and verified under idealized experimental conditions. This experiment may serve as a basis for further clinical PET/MR studies using reduced radiotracer dose as compared with conventional PET/CT studies.

Systematic evaluation of phantom fluids for simultaneous PET/MR hybrid imaging.

UNLABELLED: With the recent advent of integrated PET/MR hybrid systems, the need for simultaneous PET and MR phantom measurements arises. Phantom fluids that are used in stand-alone MR systems, especially in larger phantoms and at a high magnetic field strength, are not necessarily applicable in PET imaging and vice versa. In this study, different approaches to fluid selection were considered and systematically evaluated with respect to their usability for simultaneous PET/MR phantom imaging. METHODS: Demineralized water, water with increased electrical conductivity, a water-oil emulsion, and monoethylene and triethylene glycol were investigated in MR and PET measurements using the most common PET tracer (18)F-FDG. As an alternative to (18)F-FDG, a modified PET tracer ((18)F-fluoride Kryptofix 222 complex) was investigated toward its ability to dissolve in pure oil, which provides good signal homogeneity in MR imaging. Measurements were performed on a 3.0 T integrated PET/MR whole-body system using a National Electrical Manufacturers Association quality-standard phantom. RESULTS: All tested fluids dissolved the radiotracer (18)F-FDG homogeneously. Regarding their suitability for MR at 3.0 T, all fluids significantly improved the homogeneity compared to pure water (increase of excitation flip angle within the tested phantom by a factor of 2.0). When the use of (18)F-FDG was preferred, triethylene glycol provided the best compromise (flip angle increase by a factor of 1.13). The potential alternative tracer, (18)F-fluoride Kryptofix 222 complex, dissolved in pure oil; however, it is not optimal in its tested composition because it accumulates at the bottom of the phantom during the time of measurement. CONCLUSION: This study provides a systematic approach toward phantom fluid selection for imaging a given quality-standard body phantom--and phantoms of comparable size--at 3.0 T. For simultaneous PET/MR scans using the standard tracer (18)F-FDG, an alternative fluid to water and oil is proposed that serves as a viable option for both imaging modalities. Nevertheless, when water is preferred, ways to improve MR image homogeneity are presented. The tested alternative PET tracer enables the use of pure oil in combined scans, but the tracer composition needs to be optimized for phantom measurement applications.