Ilja Bezrukov

MRI-Based Attenuation Correction for Whole-Body PET/MRI: Quantitative Evaluation of Segmentation- and Atlas-Based Methods

PET/MRI is an emerging dual-modality imaging technology that requires new approaches to PET attenuation correction (AC). We assessed 2 algorithms for whole-body MRI-based AC (MRAC): a basic MR image segmentation algorithm and a method based on atlas registration and pattern recognition (AT&PR). Methods: Eleven patients each underwent a whole-body PET/CT study and a separate multibed whole-body MRI study. The MR image segmentation algorithm uses a combination of image thresholds, Dixon fat–water segmentation, and component analysis to detect the lungs. MR images are segmented into 5 tissue classes (not including bone), and each class is assigned a default linear attenuation value. The AT&PR algorithm uses a database of previously aligned pairs of MRI/CT image volumes. For each patient, these pairs are registered to the patient MRI volume, and machine-learning techniques are used to predict attenuation values on a continuous scale. MRAC methods are compared via the quantitative analysis of AC PET images using volumes of interest in normal organs and on lesions. We assume the PET/CT values after CT-based AC to be the reference standard. Results: In regions of normal physiologic uptake, the average error of the mean standardized uptake value was 14.1% ± 10.2% and 7.7% ± 8.4% for the segmentation and the AT&PR methods, respectively. Lesion-based errors were 7.5% ± 7.9% for the segmentation method and 5.7% ± 4.7% for the AT&PR method. Conclusion: The MRAC method using AT&PR provided better overall PET quantification accuracy than the basic MR image segmentation approach. This better quantification was due to the significantly reduced volume of errors made regarding volumes of interest within or near bones and the slightly reduced volume of errors made regarding areas outside the lungs.

MR-Based PET Attenuation Correction for PET/MR Imaging

Recent progress has allowed hybrid positron emission tomography/magnetic resonance (PET/MR) systems to make the transition from research prototypes to systems with full potential for clinical imaging. Options for directly measuring the attenuation maps, as is possible with PET/computed tomography or PET transmission scans, are not included in PET/MR scanners. New methods to compute attenuation maps from MR data have therefore been developed.

Simultaneous Whole-Body PET/MR Imaging in Comparison to PET/CT in Pediatric Oncology: Initial Results

PURPOSE To compare positron emission tomography (PET)/magnetic resonance (MR) imaging and PET/computed tomography (CT) for lesion detection and interpretation, quantification of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake, and accuracy of MR-based PET attenuation correction in pediatric patients with solid tumors. Materials and Methods This prospective study had local ethics committee and German Federal Institute for Drugs and Medical Devices approval. Written informed consent was obtained from all patients and legal guardians. Twenty whole-body (18)F-FDG PET/CT and (18)F-FDG PET/MR examinations were performed in 18 pediatric patients (median age, 14 years; range, 11-17 years). (18)F-FDG PET/CT and (18)F-FDG PET/MR data were acquired sequentially on the same day for all patients. PET standardized uptake values (SUVs) were quantified with volume of interest measurements in lesions and healthy tissues. MR-based PET attenuation correction was compared with CT-derived attenuation maps (µ-maps). Lesion detection was assessed with separate reading of PET/CT and PET/MR data. Estimates of radiation dose were derived from the applied doses of (18)F-FDG and CT protocol parameters. Descriptive statistical analyses were performed to report correlation coefficients and relative deviations for comparison of SUVs, rates of lesion detection, and percentage reductions in radiation dose. RESULTS PET SUVs showed strong correlations between PET of PET/CT (PETCT) and PET of PET/MR (PETMR) (r > 0.85 for most tissues). Apart from drawbacks of MR-based PET attenuation correction in osseous structures and lungs, similar SUVs were found on PET images corrected with CT-based µ-maps (13.1% deviation of SUVs for bone marrow and <5% deviation for other tissues). Lesion detection rate with PET/MR imaging was equivalent to that with PET/CT (61 areas of focal uptake on PETMR images vs 62 areas on PETCT images). Advantages of PET/MR were observed especially in soft-tissue regions. Furthermore, PET/MR offered significant dose reduction (73%) compared with PET/CT. CONCLUSION Pediatric oncologic PET/MR is technically feasible, showing satisfactory performance for PET quantification with SUVs similar to those of PET/CT. Compared with PET/CT, PET/MR demonstrates equivalent lesion detection rates while offering markedly reduced radiation exposure. Thus, PET/MR is a promising modality for the clinical work-up of pediatric malignancies. Online supplemental material is available for this article.

Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales

Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) is a new tool to study functional processes in the brain. Here we study brain function in response to a barrel-field stimulus simultaneously using PET, which traces changes in glucose metabolism on a slow time scale, and functional MRI (fMRI), which assesses fast vascular and oxygenation changes during activation. We found spatial and quantitative discrepancies between the PET and the fMRI activation data. The functional connectivity of the rat brain was assessed by both modalities: the fMRI approach determined a total of nine known neural networks, whereas the PET method identified seven glucose metabolism–related networks. These results demonstrate the feasibility of combined PET-MRI for the simultaneous study of the brain at activation and rest, revealing comprehensive and complementary information to further decode brain function and brain networks.

Correlation of Simultaneously Acquired Diffusion-Weighted Imaging and 2-Deoxy-[18F] fluoro-2-D-glucose Positron Emission Tomography of Pulmonary Lesions in a Dedicated Whole-Body Magnetic Resonance/Positron Emission Tomography System

ObjectiveHybrid whole-body magnetic resonance/positron emission tomography (MR/PET) systems are a new diagnostic tool enabling the simultaneous acquisition of morphologic and multiple functional data and thus allowing for a diversified characterization of oncological diseases.The aim of this study was to investigate the image and alignment quality of MR/PET in patients with pulmonary lesions and to compare the congruency of the 2 functional measurements of diffusion-weighted imaging (DWI) in MR imaging and 2-deoxy-[18F] fluoro-2-D-glucose (FDG) uptake in PET. Materials and MethodsA total of 15 patients were examined with a routine positron emission tomography/computer tomography (PET/CT) protocol and, subsequently, in a whole-body MR/PET scanner allowing for simultaneous PET and MR data acquisition. The PET and MR image quality was assessed visually using a 4-point score (1, insufficient; 4, excellent). The alignment quality of the rigidly registered PET/CT and MR/PET data sets was investigated on the basis of multiple anatomic landmarks of the lung using a scoring system from 1 (no alignment) to 4 (very good alignment). In addition, the alignment quality of the tumor lesions in PET/CT and MR/PET as well as for retrospective fusion of PET from PET/CT and MR images was assessed quantitatively and was compared between lesions strongly or less influenced by respiratory motion. The correlation of the simultaneously acquired DWI and FDG uptake in the pulmonary masses was analyzed using the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) as well as the maximum and mean standardized uptake value (SUVmax and SUVmean), respectively. In addition, the correlation of SUVmax from PET/CT data was investigated as well. On lesions 3 cm or greater, a voxelwise analysis of ADC and SUV was performed. ResultsThe visual evaluation revealed excellent image quality of the PET images (mean [SD] score, 3.6 [0.5]) and overall good image quality of DWI (mean [SD] score of 2.5 [0.5] for ADC maps and 2.7 [0.5] for diffusion-weighted images, respectively). The alignment quality of the data sets was very good in both MR/PET and PET/CT without significant differences (overall mean [SD] score of MR/PET, 3.8 [0.4]; PET/CT 3.6 [0.5]). Also, the alignment quality of the tumor lesions showed no significant differences between PET/CT and MR/PET (mean cumulative misalignment of MR/PET, 7.7 mm; PET/CT, 7.0 mm; P = 0.705) but between both modalities and a retrospective fusion (mean cumulative misalignment, 17.1 mm; P = 0.002 and P = 0.008 for PET/CT and MR/PET, respectively). Also, the comparison of the lesions strongly or less influenced by respiratory motion showed significant differences only for the retrospective fusion (21.3 mm vs 11.5 mm, respectively; P = 0.043). The ADCmin and SUVmax as measures of the cell density and glucose metabolism showed a significant reverse correlation (r = −0.80; P = 0.0006). No significant correlation was found between ADCmean and SUVmean (r = −0.42; P = 0.1392). Also, SUVmax from the PET/CT data showed significant reverse correlation to ADCmin (r = −0.62; P = 0.019). The voxelwise analysis of 5 pulmonary lesions each showed weak but significant negative correlation between ADC and SUV. ConclusionsExaminations of pulmonary lesions in a simultaneous whole-body MR/PET system provide diagnostic image quality in both modalities. Although DWI and FDG-PET reflect different tissue properties, there may very well be an association between the measures of both methods most probably because of increased cellularity and glucose metabolism of FDG-avid pulmonary lesions. A voxelwise DWI and FDG-PET correlation might provide a more sophisticated spatial characterization of pulmonary lesions.

MR-Based Attenuation Correction Methods for Improved PET Quantification in Lesions Within Bone and Susceptibility Artifact Regions

Hybrid PET/MR systems have recently entered clinical practice. Thus, the accuracy of MR-based attenuation correction in simultaneously acquired data can now be investigated. We assessed the accuracy of 4 methods of MR-based attenuation correction in lesions within soft tissue, bone, and MR susceptibility artifacts: 2 segmentation-based methods (SEG1, provided by the manufacturer, and SEG2, a method with atlas-based susceptibility artifact correction); an atlas- and pattern recognition–based method (AT&PR), which also used artifact correction; and a new method combining AT&PR and SEG2 (SEG2wBONE). Methods: Attenuation maps were calculated for the PET/MR datasets of 10 patients acquired on a whole-body PET/MR system, allowing for simultaneous acquisition of PET and MR data. Eighty percent iso-contour volumes of interest were placed on lesions in soft tissue (n = 21), in bone (n = 20), near bone (n = 19), and within or near MR susceptibility artifacts (n = 9). Relative mean volume-of-interest differences were calculated with CT-based attenuation correction as a reference. Results: For soft-tissue lesions, none of the methods revealed a significant difference in PET standardized uptake value relative to CT-based attenuation correction (SEG1, −2.6% ± 5.8%; SEG2, −1.6% ± 4.9%; AT&PR, −4.7% ± 6.5%; SEG2wBONE, 0.2% ± 5.3%). For bone lesions, underestimation of PET standardized uptake values was found for all methods, with minimized error for the atlas-based approaches (SEG1, −16.1% ± 9.7%; SEG2, −11.0% ± 6.7%; AT&PR, −6.6% ± 5.0%; SEG2wBONE, −4.7% ± 4.4%). For lesions near bone, underestimations of lower magnitude were observed (SEG1, −12.0% ± 7.4%; SEG2, −9.2% ± 6.5%; AT&PR, −4.6% ± 7.8%; SEG2wBONE, −4.2% ± 6.2%). For lesions affected by MR susceptibility artifacts, quantification errors could be reduced using the atlas-based artifact correction (SEG1, −54.0% ± 38.4%; SEG2, −15.0% ± 12.2%; AT&PR, −4.1% ± 11.2%; SEG2wBONE, 0.6% ± 11.1%). Conclusion: For soft-tissue lesions, none of the evaluated methods showed statistically significant errors. For bone lesions, significant underestimations of −16% and −11% occurred for methods in which bone tissue was ignored (SEG1 and SEG2). In the present attenuation correction schemes, uncorrected MR susceptibility artifacts typically result in reduced attenuation values, potentially leading to highly reduced PET standardized uptake values, rendering lesions indistinguishable from background. While AT&PR and SEG2wBONE show accurate results in both soft tissue and bone, SEG2wBONE uses a two-step approach for tissue classification, which increases the robustness of prediction and can be applied retrospectively if more precision in bone areas is needed.

Principles of PET/MR Imaging

Hybrid PET/MR systems have rapidly progressed from the prototype stage to systems that are increasingly being used in the clinics. This review provides an overview of developments in hybrid PET/MR systems and summarizes the current state of the art in PET/MR instrumentation, correction techniques, and data analysis. The strong magnetic field requires considerable changes in the manner by which PET images are acquired and has led, among others, to the development of new PET detectors, such as silicon photomultipliers. During more than a decade of active PET/MR development, several system designs have been described. The technical background of combined PET/MR systems is explained and related challenges are discussed. The necessity for PET attenuation correction required new methods based on MR data. Therefore, an overview of recent developments in this field is provided. Furthermore, MR-based motion correction techniques for PET are discussed, as integrated PET/MR systems provide a platform for measuring motion with high temporal resolution without additional instrumentation. The MR component in PET/MR systems can provide functional information about disease processes or brain function alongside anatomic images. Against this background, we point out new opportunities for data analysis in this new field of multimodal molecular imaging.

Comprehensive Oncologic Imaging in Infants and Preschool Children With Substantially Reduced Radiation Exposure Using Combined Simultaneous ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging: A Direct Comparison to ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

ObjectiveThe aim of this study was to evaluate the clinical applicability and technical feasibility of fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) compared with FDG PET/computed tomography (CT) in young children focusing on lesion detection, PET quantification, and potential savings in radiation exposure. MethodsTwenty examinations (10 PET/CT and 10 PET/MRI examinations) were performed prospectively in 9 patients with solid tumors (3 female, 6 male; mean age, 4.8 [1–6] years). Fluorodeoxyglucose PET/CT and FDG PET/MRI were performed sequentially after a single tracer injection. Lesion detection and analysis were performed independently in PET/CT and PET/MRI. Potential changes in diagnostic or therapeutic patient management were recorded. Positron emission tomography quantification in PET/MRI was evaluated by comparing standardized uptake values resulting from MRI-based and CT-based attenuation correction. Effective radiation doses of PET and CT were estimated. ResultsTwenty-one PET-positive lesions were found congruently in PET/CT and PET/MRI. Magnetic resonance imaging enabled significantly better detection of morphologic PET correlates compared with CT. Eight suspicious PET-negative lesions were identified by MRI, of which one was missed in CT. Sensitivity, specificity, and accuracy for correct lesion classification were not significantly different (90%, 47%, and 62% in PET/CT; 100%, 68%, and 79% in PET/MRI, respectively). In 4 patients, the use of PET/MRI resulted in a potential change in diagnostic management compared with PET/CT, as local and whole-body staging could be performed within 1 single examination. In 1 patient, PET/MRI initiated a change in therapeutic management. Positron emission tomography quantification using MRI-based attenuation correction was accurate compared with CT-based attenuation correction. Higher standardized uptake value deviations of about 18% were observed in the lungs due to misclassification in MRI-based attenuation maps. Potential reduction in radiation dose was 48% in PET/MRI compared with PET/CT (P < 0.05). ConclusionsFDG PET/MRI is at least equivalent to FDG PET/CT for oncologic imaging in young children. Specifically, superior soft tissue contrast of MRI results in higher confidence in lesion interpretation. Substantial savings in radiation exposure can be achieved, and the number of necessary imaging examinations can be reduced using PET/MRI compared with PET/CT.

Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging

PurposeClinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging.MethodsWe employed two MRCA: Lumirem® (oral) and Gadovist® (IV). First, we determined their reference PET attenuation values using a PET transmission scan (ECAT-EXACT HR+, Siemens) and a CT scan (PET/CT Biograph 16 HI-REZ, Siemens). Second, we evaluated the attenuation of PET signals in the presence of MRCA. Phantoms were filled with clinically relevant concentrations of MRCA in a background of water and 18F-fluoride, and imaged using a PET/CT scanner (Biograph 16 HI-REZ, Siemens) and a PET/MR scanner (Biograph mMR, Siemens). Third, we investigated the effect of clinically relevant volumes of MRCA on MR-based AC using human pilot data: a patient study employing Gadovist® (IV) and a volunteer study employing two different oral MRCA (Lumirem® and pineapple juice). MR-based attenuation maps were calculated following Dixon-based fat–water segmentation and an external atlas-based and pattern recognition (AT&PR) algorithm.ResultsIV and oral MRCA in clinically relevant concentrations were found to have PET attenuation values similar to those of water. The phantom experiments showed that under clinical conditions IV and oral MRCA did not yield additional attenuation of PET emission signals. Patient scans showed that PET attenuation maps are not biased after the administration of IV MRCA but may be biased, however, after ingestion of iron oxide-based oral MRCA when segmentation-based AC algorithms are used. Alternative AC algorithms, such as AT&PR, or alternative oral contrast agents, such as pineapple juice, can yield unbiased attenuation maps.ConclusionIn clinical PET/MR scenarios MRCA are not expected to lead to markedly increased attenuation of the PET emission signals. MR-based attenuation maps may be biased by oral iron oxide-based MRCA unless advanced AC algorithms are used.

Assessment of murine brain tissue shrinkage caused by different histological fixatives using magnetic resonance and computed tomography imaging

Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P < 0.001), followed by PFA (60.2%, P<0.001) and NBF (58.6%, P<0.001). The zinc-based fixative revealed a low shrinkage with only 33.5% (P<0.001). Compared to NBF, the zinc-based fixative shows a slightly higher degree of deformations, but is still more homogenous than PFA. Tissue shrinkage can be monitored non-invasively with CT and MR. Zinc-based fixative causes the smallest degree of brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies.