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When this article was written, it coincided with the 11th anniversary of the installation of our PET/MR device in Munich. In fact, this was the first fully integrated device to be in clinical use. During this time, we have observed many interesting behaviors, to put it kindly. However, it is more critical that in this process, our understanding of the system also improved - including the advantages and limitations from a technical, logistical, and medical perspective. The last decade of PET/MRI research has certainly been characterized by most sites looking for a "key application." There were many ideas in this context and before and after the devices became available, some of which were based on the earlier work with integrating data from single devices. These involved validating classical PET methods with MRI (eg, perfusion or oncology diagnostics). More important, however, were the scenarios where intermodal synergies could be expected. In this review, we look back on this decade-long journey, at the challenges overcome and those still to come.

Purpose To evaluate the performance of combined PET and multiparametric MRI (mpMRI) radiomics for the group-wise prediction of postsurgical Gleason scores (psGSs) in primary prostate cancer (PCa) patients. Methods Patients with PCa, who underwent [68 Ga]Ga-PSMA-11 PET/MRI followed by radical prostatectomy, were included in this retrospective analysis (n = 101). Patients were grouped by psGS in three categories: ISUP grades 1–3, ISUP grade 4, and ISUP grade 5. mpMRI images included T1-weighted, T2-weighted, and apparent diffusion coefficient (ADC) map. Whole-prostate segmentations were performed on each modality, and image biomarker standardization initiative (IBSI)-compliant radiomic features were extracted. Nine support vector machine (SVM) models were trained: four single-modality radiomic models (PET, T1w, T2w, ADC); three PET + MRI double-modality models (PET + T1w, PET + T2w, PET + ADC), and two baseline models (one with patient data, one image-based) for comparison. A sixfold stratified cross-validation was performed, and balanced accuracies (bAcc) of the predictions of the best-performing models were reported and compared through Student’s t-tests. The predictions of the best-performing model were compared against biopsy GS (bGS). Results All radiomic models outperformed the baseline models. The best-performing (mean ± stdv [%]) single-modality model was the ADC model (76 ± 6%), although not significantly better (p > 0.05) than other single-modality models (T1w: 72 ± 3%, T2w: 73 ± 2%; PET: 75 ± 5%). The overall best-performing model combined PET + ADC radiomics (82 ± 5%). It significantly outperformed most other double-modality (PET + T1w: 74 ± 5%, p = 0.026; PET + T2w: 71 ± 4%, p = 0.003) and single-modality models (PET: p = 0.042; T1w: p = 0.002; T2w: p = 0.003), except the ADC-only model (p = 0.138). In this initial cohort, the PET + ADC model outperformed bGS overall (82.5% vs 72.4%) in the prediction of psGS. Conclusion All single- and double-modality models outperformed the baseline models, showing their potential in the prediction of GS, even with an unbalanced cohort. The best-performing model included PET + ADC radiomics, suggesting a complementary value of PSMA-PET and ADC radiomics.

Purpose After a decade of PET/MR, the case of attenuation correction (AC) remains open. The initial four-compartment (air, water, fat, soft tissue) Dixon-based AC scheme has since been expanded with several features, the latest being MR field-of-view extension and a bone atlas. As this potentially changes quantification, we evaluated the impact of these features in PET AC in prostate cancer patients. Methods Two hundred prostate cancer patients were examined with either 18F- or 68Ga-prostate-specific membrane antigen (PSMA) PET/MR. Qualitative and quantitative analysis (SUVmean, SUVmax, correlation, and statistical significance) was performed on images reconstructed using different AC schemes: Dixon, Dixon+MLAA, Dixon+HUGE, and Dixon+HUGE+bones for 18F-PSMA data; Dixon and Dixon+bones for 68Ga-PSMA data. Uptakes were compared using linear regression against standard Dixon. Results High correlation and no visually perceivable differences between all evaluated methods (r > 0.996) were found. The mean relative difference in lesion uptake of 18F-PSMA and 68Ga-PSMA remained, respectively, within 4% and 3% in soft tissue, and within 10% and 9% in bones for all evaluated methods. Bone registration errors were detected, causing mean uptake change of 5% in affected lesions. Conclusions Based on these results and the encountered bone atlas registration inaccuracy, we deduce that including bones and extending the MR field-of-view did not introduce clinically significant differences in PSMA diagnostic accuracy and tracer uptake quantification in prostate cancer pelvic lesions, facilitating the analysis of serial studies respectively. However, in the absence of ground truth data, we advise against atlas-based methods when comparing serial scans for bone lesions.

The aim of this study was to demonstrate the feasibility of high-resolution 3-dimensional aortic vessel wall imaging using a novel elastin-specific magnetic resonance contrast agent (ESMA) in a large animal model.The thoracic aortic vessel wall of 6 Landrace pigs was imaged using a novel ESMA and a nonspecific control agent. On day 1, imaging was performed before and after the administration of a nonspecific control agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Bayer Schering AG, Berlin, Germany). On day 3, identical scans were repeated before and after the administration of a novel ESMA (Lantheus Medical Imaging, North Billerica, Massachusetts). Three-dimensional inversion recovery gradient echo delayed-enhancement imaging and magnetic resonance (MR) angiography of the thoracic aortic vessel wall were performed on a 1.5-T MR scanner (Achieva; Philips Medical Systems, the Netherlands). The signal-to-noise ratio and the contrast-to-noise ratio of arterial wall enhancement, including the time course of enhancement, were assessed for ESMA and Gd-DTPA. After the completion of imaging sessions, histology, electron microscopy, and inductively coupled plasma mass spectroscopy were performed to localize and quantify the gadolinium bound to the arterial vessel wall.Administration of ESMA resulted in a strong enhancement of the aortic vessel wall on delayed-enhancement imaging, whereas no significant enhancement could be measured with Gd-DTPA. Ninety to 100 minutes after the administration of ESMA, significantly higher signal-to-noise ratio and contrast-to-noise ratio could be measured compared with the administration of Gd-DTPA (45.7 ± 9.6 vs 13.2 ± 3.5, P0.05 and 41.9 ± 9.1 vs 5.2 ± 2.0, P0.05). A significant correlation (0.96; P0.01) between area measurements derived from ESMA scans and aortic MR angiography scans could be found. Electron microscopy and inductively coupled plasma mass spectroscopy confirmed the colocalization of ESMA with elastic fibers.We demonstrate the feasibility of aortic vessel wall imaging using a novel ESMA in a large animal model under conditions resembling a clinical setting. Such an approach could be useful for the fast 3-dimensional assessment of the arterial vessel wall in the context of atherosclerosis, aortic aneurysms, and hypertension.

ObjectivesOur aim was to determine whether serial contrast-enhanced cardiac magnetic resonance (CE-CMR) is useful for the characterization of tissue signal changes within the coronary vessel wall in patients after acute myocardial infarction (AMI).BackgroundInflammation plays a key role in the development of AMI. CE-CMR of the vessel wall has been found useful for the characterization of inflammatory tissue signal changes in patients with carotid artery stenosis, giant cell arteritis, or Takayasu's arteritis; however, it has never been serially performed in the coronary artery wall in patients with acute and chronic myocardial infarction using a gadolinium-based contrast medium and compared with systemic markers of inflammation.MethodsCE-CMR using a T1-weighted 3-dimensional gradient echo inversion recovery sequence of the coronary artery wall and 0.2 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid was performed in 10 patients with AMI 6 days and 3 months after coronary intervention and in 9 subjects without coronary artery disease on invasive coronary angiography. Contrast-to-noise ratio (CNR) within the coronary artery wall was quantified in comparison with blood signal.ResultsPatients with AMI demonstrated a significantly increased coronary vessel wall enhancement 6 days after infarction compared with normal subjects (CNR 7.8 ± 4.4 vs. 5.3 ± 3.2, p < 0.001). Three months after infarction, CNR decreased to 6.5 ± 4.7 (p < 0.03). This decrease paralleled declines in C-reactive protein. Angiographically normal segments showed no contrast changes, but CNR significantly decreased in stenotic segments, from 10.9 ± 3.8 to 6.8 ± 5.0 (p < 0.002), resulting in a reduction of enhanced segments from 70% to 25% (p < 0.01).ConclusionsSerial CE-CMR identified changes in spatial extent and intensity of coronary contrast enhancement in patients after AMI. This technique may be useful for the characterization of transient coronary tissue signal changes, which may represent edema or inflammation during the post-infarction phase. In addition, CE-CMR may offer the potential for visualization of inflammatory activity in atherosclerosis associated with acute coronary syndromes.

Positron emission tomography (PET) agents targeting the prostate-specific membrane antigen (PSMA) are currently under broad clinical and scientific investigation. (68)Ga-PSMA HBED-CC constitutes the first (68)Ga-labelled PSMA-inhibitor and has evolved as a promising agent for imaging PSMA expression in vivo. The aim of this study was to evaluate the whole-body distribution and radiation dosimetry of this new probe.Five patients with a history or high suspicion of prostate cancer were injected intravenously with a mean of 139.8 ± 13.7 MBq of (68)Ga-PSMA HBED-CC (range 120-158 MBq). Four static skull to mid-thigh scans using a whole-body fully integrated PET/MR-system were performed 10 min, 60 min, 130 min, and 175 min after the tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses (ED) were calculated using OLINDA/EXM.Injection of a standard activity of 150 MBq (68)Ga-PSMA HBED-CC resulted in a median effective dose of 2.37 mSv (Range 1.08E-02 - 2.46E-02 mSv/MBq). The urinary bladder wall (median absorbed dose 1.64E-01 mGv/MBq; range 8.76E-02 - 2.91E-01 mGv/MBq) was the critical organ, followed by the kidneys (median absorbed dose 1.21E-01 mGv/MBq; range 7.16E-02 - 1.75E-01), spleen (median absorbed dose 4.13E-02 mGv/MBq; range 1.57E-02 - 7.32E-02 mGv/MBq) and liver (median absorbed dose 2.07E-02 mGv/MBq; range 1.80E-02 - 2.57E-02 mGv/MBq). No drug-related pharmacological effects occurred.The use of (68)Ga-PSMA HBED-CC results in a relatively low radiation exposure, delivering organ doses that are comparable to those of other (68)Ga-labelled PSMA-inhibitors used for PET-imaging. Total effective dose is lower than for other PET-agents used for prostate cancer imaging (e.g. (11)C- and (18)F-Choline).

During [(90)Y]DOTATOC therapy, for determination of kidney doses a conventional approach using co-injected [(111)In]DOTATOC was evaluated for validity, reliability and reproducibility as well as for the influence of methodological variations and bremsstrahlung. Biologically effective doses were estimated by calculating the relative effectiveness (RE) of kidney doses.Fractionated [(90)Y]DOTATOC therapy (n=20 patients, 3.1+/-0.7 GBq/therapy cycle, 45 therapy cycles) included co-injection of 157+/-37 MBq [(111)In]DOTATOC and a nephroprotective infusion regimen. From serial gamma camera/probe measurements, individual region of interest (ROI) sets were established and kidney doses were determined according to MIRDOSE3 (corrected for individual kidney mass) by use of three methodological variants: (1) correction for interfering organs (liver/spleen) and background activity, (2) correction for interfering organs alone and (3) no corrections. A phantom study was performed with (111) In alone and with (111)In +(90)Y to estimate the influence of (90)Y bremsstrahlung.Mean kidney dose (method 1, n=20 patients, 20 therapy cycles) was 1.51+/-0.60 Gy/GBq [(90)Y]DOTATOC (1.41+/-0.48 Gy/GBq for n=20 patients, 45 therapy cycles). With partial correction (method 2) or no correction (method 3) for interfering activity, kidney doses increased significantly, to 2.71+/-1.26 Gy/GBq and 3.15+/-1.22 Gy/GBq, respectively. The span of REs ranged from 1.02 to 1.24. Inter-observer variability was as high as +/-32% (+/-2SD). (90)Y bremsstrahlung accounted for a 4-11% underestimation of obtained target activity.The obtained kidney doses are highly influenced by methodological variations. Full correction for interfering activity clearly underestimates kidney doses. By comparison, (90)Y bremsstrahlung and variability in the relative effectiveness of kidney doses cause minor bias. Inter-observer variability must be considered when interpreting kidney doses.

We present an approach for head MR-based attenuation correction (AC) based on the Statistical Parametric Mapping 8 (SPM8) software, which combines segmentation- and atlas-based features to provide a robust technique to generate attenuation maps (μ maps) from MR data in integrated PET/MR scanners. Methods: Coregistered anatomic MR and CT images of 15 glioblastoma subjects were used to generate the templates. The MR images from these subjects were first segmented into 6 tissue classes (gray matter, white matter, cerebrospinal fluid, bone, soft tissue, and air), which were then nonrigidly coregistered using a diffeomorphic approach. A similar procedure was used to coregister the anatomic MR data for a new subject to the template. Finally, the CT-like images obtained by applying the inverse transformations were converted to linear attenuation coefficients to be used for AC of PET data. The method was validated on 16 new subjects with brain tumors (n = 12) or mild cognitive impairment (n = 4) who underwent CT and PET/MR scans. The μ maps and corresponding reconstructed PET images were compared with those obtained using the gold standard CT-based approach and the Dixon-based method available on the Biograph mMR scanner. Relative change (RC) images were generated in each case, and voxel- and region-of-interest–based analyses were performed. Results: The leave-one-out cross-validation analysis of the data from the 15 atlas-generation subjects showed small errors in brain linear attenuation coefficients (RC, 1.38% ± 4.52%) compared with the gold standard. Similar results (RC, 1.86% ± 4.06%) were obtained from the analysis of the atlas-validation datasets. The voxel- and region-of-interest–based analysis of the corresponding reconstructed PET images revealed quantification errors of 3.87% ± 5.0% and 2.74% ± 2.28%, respectively. The Dixon-based method performed substantially worse (the mean RC values were 13.0% ± 10.25% and 9.38% ± 4.97%, respectively). Areas closer to the skull showed the largest improvement. Conclusion: We have presented an SPM8-based approach for deriving the head μ map from MR data to be used for PET AC in integrated PET/MR scanners. Its implementation is straightforward and requires only the morphologic data acquired with a single MR sequence. The method is accurate and robust, combining the strengths of both segmentation- and atlas-based approaches while minimizing their drawbacks.

We describe a new MR-based attenuation correction (MRAC) method for neurological studies performed using integrated PET/MR scanners. The method, combining the advantages of image segmentation and atlas-based approaches to generate a high-resolution template, is based on the widely available SPM8 software and provides robust and accurate linear attenuation coefficients (LACs) for head while requiring minimal user interaction. Atlas generation: 3T MR and CT images from 15 glioblastoma subjects were used to generate the high-resolution atlas. MR images were segmented into 6 tissue classes: GM, WM, CSF, soft tissue, bone and air)[1]. Tissue classes were then coregistered using an iterative diffeomorphic image registration algorithm [2] to form the template. Atlas validation: The template was validated on 16 subjects. SyN [3] and IRTK [4], considered state-of-the-art for non-rigid image registration[5], were used for comparison. Final attenuation maps were created from the warped CT atlas following [6]. PET images were then reconstructed using the proposed methods as well as the manufacturer’s built-in method (dual-echo Dixon-VIBE sequence) [7] and compared to the gold standard CT-based attenuation correction (CTAC). The qualitative and quantitative analysis of the attenuation maps revealed that the SPM8-based method produces very robust results (Figure ​(Figure1).1). In terms of the PET data quantification, we observed improvements of > 70% compared to the VIBE-based method (Table ​(Table11 and Figure ​Figure2).2). When compared to SyN-based image registration, the SPM8 approach showed improved global results on the brain area (Figures ​(Figures11 and ​and22). Figure 1 Comparison of LACs from a validation subject for our proposed method (A), the SyN method (B) and the manufacturer’s built-in Dixon method (C) to the gold standard CTAC (D). Image differences with respect to the gold standard CTAC of our method ... Table 1 Summary of voxel- and ROI-based results between our method (atlas) and the current manufacturer’s method (Dixon) Figure 2 PET images from a validation subject reconstructed with our proposed method (A), with the SyN method (B) and with the manufacturer’s built-in Dixon method (C), compared with the gold standard CTAC (D). Relative changes (in % with respect to gold ... We presented a new MRAC technique for brain images acquired on simultaneous PET/MR scanners. The new approach relies on segmentation- and atlas-based features to provide robust and more accurate LACs than using state-of-art non-rigid image registration while avoiding sophisticated user input or interaction.

Background— The extracellular matrix (ECM) plays an important role in the pathogenesis of atherosclerosis and in-stent restenosis. Elastin is an essential component of the ECM. ECM degradation can lead to plaque destabilization, whereas enhanced synthesis typically leads to vessel wall remodeling resulting in arterial stenosis or in-stent restenosis after stent implantation. The objective of this study was to demonstrate the feasibility of MRI of vascular remodeling using a novel elastin-binding contrast agent (BMS-753951). Methods and Results— Coronary injury was induced in 6 pigs by endothelial denudation and stent placement. At day 28, delayed-enhancement MRI coronary vessel wall imaging was performed before and after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). Two days later, DE-MRI was repeated after administration of BMS-753951. Contrast-to-noise-ratio and areas of enhancement were determined. Delayed-enhancement MRI with BMS-753951 caused strong enhancement of the aortic, pulmonary artery, and injured coronary artery walls, whereas Gd-DTPA did not. Delayed-enhancement MRI of the stented coronary artery with BMS-753951 yielded a 3-fold higher contrast-to-noise-ratio when compared with the balloon-injured and control coronary artery (21±6 versus 7±3 versus 6±4; P R 2 =0.86, P Conclusions— We demonstrate the noninvasive detection and quantification of vascular remodeling in an animal model of coronary vessel wall injury using an elastin-specific MR contrast agent. This novel approach may be useful for the assessment of coronary vessel wall remodeling in patients with suspected coronary artery disease. Further studies in atherosclerotic animal models and degenerative ECM disease are now warranted.

Background Expansion of myocardial extracellular volume (ECV) as detected by native and post contrast T1 mapping has been associated with different types of cardiomyopathy. We hypothesize that fully quantitative evaluation of MR perfusion imaging can localize and quantify edematous ECV expansion after acute coronary events with sensitivity equivalent to ECV measurements based on T1 mapping or the detection of corresponding inflammatory and metabolic processes with FDG-PET.